Difference between revisions of "Small cell lung cancer"
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− | + | [[#top|Back to Top]] | |
− | + | </div> | |
+ | {{#lst:Editorial board transclusions|thoracic}} | ||
+ | ''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Small cell lung cancer_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Small cell lung cancer - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''. | ||
{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
|- | |- | ||
− | |<div style="background-color: # | + | |<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div> |
− | <div style="background-color: # | + | <div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div> |
|} | |} | ||
{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
+ | =Guidelines= | ||
+ | '''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.''' | ||
+ | ==[https://www.asco.org/ ASCO]== | ||
+ | *'''2021:''' Daly et al. [https://doi.org/10.1200/jco.20.03364 Radiation Therapy for Small-Cell Lung Cancer: ASCO Guideline Endorsement of an ASTRO Guideline] [https://pubmed.ncbi.nlm.nih.gov/33502911 PubMed] | ||
+ | *'''2020:''' Schneider et al. [https://doi.org/10.1200/jco.19.02748 Lung Cancer Surveillance After Definitive Curative-Intent Therapy: ASCO Guideline] [https://pubmed.ncbi.nlm.nih.gov/31829901 PubMed] | ||
+ | *'''2015:''' Rudin et al. [https://doi.org/10.1200/JCO.2015.63.7918 Treatment of small-cell lung cancer: American Society of Clinical Oncology endorsement of the American College of Chest Physicians guideline] [https://pubmed.ncbi.nlm.nih.gov/26351333/ PubMed] | ||
+ | ==ASCO-Ontario Health== | ||
+ | *'''2023:''' Khurshid et al. [https://doi.org/10.1200/jco.23.01435 Systemic Therapy for Small-Cell Lung Cancer: ASCO-Ontario Health (Cancer Care Ontario) Guideline] [https://pubmed.ncbi.nlm.nih.gov/37820295/ PubMed] | ||
− | + | ==[https://www.esmo.org/ ESMO]== | |
− | ==ESMO== | + | *'''2021:''' Dingemans et al. [https://doi.org/10.1016/j.annonc.2021.03.207 Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464246/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33864941/ PubMed] |
− | *[ | + | **'''2013:''' Früh et al. [https://doi.org/10.1093/annonc/mdt178 Small-cell lung cancer (SCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.] [https://pubmed.ncbi.nlm.nih.gov/23813929/ PubMed] |
+ | **'''2010:''' Sørensen et al. [https://doi.org/10.1093/annonc/mdq172 Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/20555060/ PubMed] | ||
+ | **'''2009:''' Sørensen & Felip. [https://doi.org/10.1093/annonc/mdp133 Small-cell lung cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/19454469/ PubMed] | ||
+ | **'''2005:''' Felip et al. [https://doi.org/10.1093/annonc/mdi829 ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of small-cell lung cancer (SCLC)] [https://pubmed.ncbi.nlm.nih.gov/15888744/ PubMed] | ||
+ | **'''2001:''' [https://doi.org/10.1023/a:1017436818940 ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of small-cell lung cancer (SCLC)] [https://pubmed.ncbi.nlm.nih.gov/11583181/ PubMed] | ||
==NCCN== | ==NCCN== | ||
− | *[https://www.nccn.org/ | + | *[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1462 NCCN Guidelines - Small Cell Lung Cancer] |
+ | **'''2021:''' Ganti et al. [https://doi.org/10.6004/Jnccn.2021.0058 Small Cell Lung Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10203822/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34902832/ PubMed] | ||
+ | **'''2013:''' Kalemkerian et al. [https://doi.org/10.6004/Jnccn.2013.0011 Small cell lung cancer.] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715060/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23307984/ PubMed] | ||
+ | **'''2011:''' Kalemkerian et al. [https://doi.org/10.6004/Jnccn.2011.0092 Small cell lung cancer.] [https://pubmed.ncbi.nlm.nih.gov/21975911/ PubMed] | ||
+ | **'''2006:''' Johnson et al. [https://doi.org/10.6004/Jnccn.2006.0050 Small cell lung cancer clinical practice guidelines in oncology.] [https://pubmed.ncbi.nlm.nih.gov/16813728/ PubMed] | ||
+ | **'''2004:''' Authors not listed. [https://doi.org/10.6004/Jnccn.2004.0012 Small cell lung cancer. Clinical practice guidelines in oncology.] [https://pubmed.ncbi.nlm.nih.gov/19777703/ PubMed] | ||
+ | |||
+ | ==SITC== | ||
+ | *'''2022:''' Govindan et al. [https://doi.org/10.1136/jitc-2021-003956 Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lung cancer and mesothelioma] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157337/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35640927/ PubMed] | ||
− | =Limited stage= | + | =Limited stage, induction= |
− | ==Carboplatin, Etoposide ( | + | ==Carboplatin & Etoposide (CE) {{#subobject:f0013f|Regimen=1}}== |
− | {| class="wikitable" style=" | + | EP: '''<u>E</u>'''toposide, '''<u>P</u>'''araplatin (Carboplatin) |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, 2 days of oral etoposide per cycle {{#subobject:89f0ef|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1093/jnci/djp200 Lee et al. 2009 (LLCG-STUDY-12)] | ||
+ | |2003-2006 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[Stub#Carboplatin_.26_Etoposide_.28CE.29_.26_Thalidomide|CE & Thalidomide]], then RT | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 10.5 vs 10.1 mo<br>(HR 0.92, 95% CI 0.79-1.08) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once on day 1, then 100 mg PO twice per day on days 2 & 3 | ||
+ | '''21-day cycle for up to 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *LLCG-STUDY-12, patients with PR/CR: Definitive [[#Radiation_therapy|thoracic radiotherapy]] and [[#Whole_brain_irradiation|prophylactic cranial irradiation]], approximately 3 weeks after the last cycle, "according to local practice". | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 1 day of oral etoposide per cycle {{#subobject:3cbc9f|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1093/jnci/djp200 Lee et al. 2009 (LLCG-STUDY-12)] | ||
+ | |2003-2006 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[Stub#Carboplatin_.26_Etoposide_.28CE.29_.26_Thalidomide|CE & Thalidomide]], then RT | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 10.5 vs 10.1 mo<br>(HR 0.92, 95% CI 0.79-1.08) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2, then 100 mg PO twice per day on day 3 | ||
+ | '''21-day cycle for up to 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *LLCG-STUDY-12, patients with PR/CR: Definitive [[#Radiation_therapy|thoracic radiotherapy]] and [[#Whole_brain_irradiation|prophylactic cranial irradiation]], approximately 3 weeks after the last cycle, "according to local practice". | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''LLCG-STUDY-12:''' Lee SM, Woll PJ, Rudd R, Ferry D, O'Brien M, Middleton G, Spiro S, James L, Ali K, Jitlal M, Hackshaw A. Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2009 Aug 5;101(15):1049-57. Epub 2009 Jul 16. [https://doi.org/10.1093/jnci/djp200 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19608997/ PubMed] [https://clinicaltrials.gov/study/NCT00061919 NCT00061919] | ||
+ | ==Cisplatin & Etoposide (EP) {{#subobject:189bcc|Regimen=1}}== | ||
+ | EP: '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:dd9b40|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.1985.3.11.1471 Evans et al. 1985] | ||
+ | |1981-1984 | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | ''Note: Patients with limited stage disease responding to therapy received [[#Whole_brain_irradiation|prophylactic cranial irradiation]], 400 cGy fractions once per day x 5 fractions (total dose: 2000 cGy) over 5 days between cycles 3 and 4.'' | |
− | < | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV slow push once per day on days 1 to 3, '''given second''' | ||
+ | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over at least 30 minutes once per day on days 1 to 3, '''given first''' | ||
+ | ====Supportive therapy==== | ||
+ | *[[Dexamethasone (Decadron)]] 10 mg IV once per day on days 1 to 3, prior to chemotherapy | ||
+ | *[[Metoclopramide (Reglan)]] 10 mg IV or PO once per day on days 1 to 3, prior to chemotherapy | ||
+ | *[[Prochlorperazine (Compazine)]] 10 mg IM or PO once per day on days 1 to 3, prior to chemotherapy | ||
+ | *"No special efforts were made to hydrate the patients," though PO fluid intake was encouraged, and 500 mL normal saline was given with etoposide infusion. | ||
+ | '''21- to 28-day cycle for 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *Definitive [[#Radiation_therapy|thoracic radiation]] | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. [https://doi.org/10.1200/jco.1985.3.11.1471 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2997406/ PubMed] | ||
− | ===Regimen #1 {{#subobject:9e4385|Variant=1}}=== | + | =Limited stage, definitive chemoradiotherapy= |
− | {| | + | ==Carboplatin, Etoposide, RT {{#subobject:6c0ece|Regimen=1}}== |
− | | | + | EP & RT: '''<u>E</u>'''toposide, '''<u>P</u>'''araplatin (Carboplatin), '''<u>R</u>'''adiation '''<u>T</u>'''herapy |
− | |[[Levels_of_Evidence#Evidence| | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | | | + | ===Regimen variant #1 {{#subobject:9e4385|Variant=1}}=== |
− | |[[Levels_of_Evidence# | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1023/a:1012295131640 Skarlos et al. 2001] |
− | |style="background-color:# | + | |1993-1999 |
− | |Carboplatin, Etoposide, early HTRT | + | | style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic) |
− | |style="background-color:# | + | |[[#Carboplatin.2C_Etoposide.2C_RT|Carboplatin, Etoposide, RT]]; early HTRT |
+ | | style="background-color:#d9ef8b" |Might have superior ORR (primary endpoint) | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Carboplatin (Paraplatin)]] AUC 6 IV over | + | ====Chemotherapy==== |
+ | *[[Carboplatin (Paraplatin)]] AUC 6 IV over 60 minutes once on day 1, '''given first, before etoposide''' | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 3, '''given second, after carboplatin''' | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 3, '''given second, after carboplatin''' | ||
− | *Concurrent hyperfractionated | + | ====Radiotherapy==== |
− | + | *Concurrent [[External beam radiotherapy|hyperfractionated thoracic radiation therapy (HTRT)]], 150 cGy fractions given twice per day (at least 4, but preferably 6 hours between fractions) x 30 fractions (total dose: 4500 cGy) over 3 weeks. Skarlos et al. 2001 examined two different timings for radiation therapy. There was no significant difference between early vs. late HTRT, though there was a trend toward higher response rate for late HTRT. Early HTRT is given during cycle 1 of chemotherapy; late HTRT is given during cycle 4 of chemotherapy. | |
'''21-day cycle for up to 6 cycles''' | '''21-day cycle for up to 6 cycles''' | ||
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | + | ====Subsequent treatment==== | |
− | ==== | + | *Skarlos et al. 2001, patients with CR: Prophylactic [[#Whole_brain_irradiation|cranial irradiation]] |
− | * | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ===Regimen #2 {{#subobject:bb6fc|Variant=1}}=== | + | ===Regimen variant #2 {{#subobject:bb6fc|Variant=1}}=== |
− | {| | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | | | + | !style="width: 33%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.1999.17.11.3540 Okamoto et al. 1999] |
− | |style="background-color:# | + | |1995-1996 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
− | + | ====Eligibility criteria==== | |
− | ==== | + | *At least 70 years old |
− | *[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 1, '''given first | + | </div> |
− | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 3, '''given second | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *Thoracic radiation | + | ====Chemotherapy==== |
+ | *[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 1, '''given first''' | ||
+ | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 3, '''given second''' | ||
+ | ====Radiotherapy==== | ||
+ | *[[External beam radiotherapy|Thoracic radiation]], '''given third''' | ||
*Palliative radiation therapy was allowed to control persistent pain from bony metastases | *Palliative radiation therapy was allowed to control persistent pain from bony metastases | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Dexamethasone (Decadron)]] 8 mg IV once per day on days 1 to 3, prior to chemotherapy |
− | *[[Dexamethasone (Decadron)]] 8 mg IV once per day on days 1 to 3 prior to chemotherapy | + | *[[Granisetron]] 40 mcg/kg IV once per day on days 1 to 3, prior to chemotherapy |
− | *[[Granisetron | + | *[[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 2 mcg/kg SC given for grade 3 or greater leukopenia/neutropenia |
− | *[[ | ||
− | |||
'''28-day cycle for up to 4 cycles''' | '''28-day cycle for up to 4 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- Presented in part at the Thirty-Fourth Annual Meeting of the American Society of Clinical Oncology, Los Angeles, CA, May 16-19, 1998. --> | <!-- Presented in part at the Thirty-Fourth Annual Meeting of the American Society of Clinical Oncology, Los Angeles, CA, May 16-19, 1998. --> | ||
− | # Okamoto H, Watanabe K, Nishiwaki Y, Mori K, Kurita Y, Hayashi I, Masutani M, Nakata K, Tsuchiya S, Isobe H, Saijo N. Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer. J Clin Oncol. 1999 Nov;17(11):3540-5. [ | + | # Okamoto H, Watanabe K, Nishiwaki Y, Mori K, Kurita Y, Hayashi I, Masutani M, Nakata K, Tsuchiya S, Isobe H, Saijo N. Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer. J Clin Oncol. 1999 Nov;17(11):3540-5. [https://doi.org/10.1200/jco.1999.17.11.3540 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10550152/ PubMed] |
− | # Skarlos DV, Samantas E, Briassoulis E, Panoussaki E, Pavlidis N, Kalofonos HP, Kardamakis D, Tsiakopoulos E, Kosmidis P, Tsavdaridis D, Tzitzikas J, Tsekeris P, Kouvatseas G, Zamboglou N, Fountzilas G. Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol. 2001 Sep;12(9):1231-8. [ | + | # Skarlos DV, Samantas E, Briassoulis E, Panoussaki E, Pavlidis N, Kalofonos HP, Kardamakis D, Tsiakopoulos E, Kosmidis P, Tsavdaridis D, Tzitzikas J, Tsekeris P, Kouvatseas G, Zamboglou N, Fountzilas G; Hellenic Cooperative Oncology Group. Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol. 2001 Sep;12(9):1231-8. [https://doi.org/10.1023/a:1012295131640 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11697833/ PubMed] |
− | + | ==Cisplatin, Etoposide, RT {{#subobject:fb5cd7|Regimen=1}}== | |
− | == | + | EP & RT: '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin), '''<u>R</u>'''adiation '''<u>T</u>'''herapy |
− | {| class="wikitable" style=" | + | <br>PE + RT: '''<u>P</u>'''latinol (Cisplatin), '''<u>E</u>'''toposide, '''<u>R</u>'''adiation '''<u>T</u>'''herapy |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, 60/360/45 {{#subobject:63584c|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/NEJM199901283400403 Turrisi et al. 1999 (Intergroup 0096)] | ||
+ | |1989-1992 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |[[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]]; once per day RT | ||
+ | | style="background-color:#91cf60" |Seems to have superior OS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | ====Radiotherapy==== | ||
+ | *Concurrent [[External_beam_radiotherapy|radiation therapy]], 150 cGy fractions given twice per day x 30 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 4500 cGy) | ||
+ | '''21-day cycle for 4 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *After completing 4 cycles of chemotherapy, patients were restaged. Because of the high rate of brain metastases (50%), patients with CR were offered prophylactice [[#Whole_brain_irradiation|cranial irradiation]] | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 70/300/52.5, early RT {{#subobject:97533b|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 17%"|Study | ||
+ | !style="width: 15%"|Dates of enrollment | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 17%"|Comparator | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1093/annonc/mdt140 Sun et al. 2013 (SMC 2003-02-016)] | ||
+ | |2003-2010 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]]; late RT | ||
+ | | style="background-color:#eeee01" |Non-inferior CR rate | ||
+ | | style="background-color:#fc8d59" |Seems to have higher rates of neutropenic fever | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | < | + | ====Chemotherapy==== |
− | + | *[[Cisplatin (Platinol)]] 70 mg/m<sup>2</sup> IV once on day 1 | |
− | ===Regimen {{#subobject: | + | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 |
− | {| | + | ====Radiotherapy==== |
− | | | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]], 210 cGy fractions x 25 fractions over 5 weeks, given during cycle 1 of chemotherapy (total dose: 5250 cGy) |
− | |[[Levels_of_Evidence#Evidence| | + | '''21-day cycle for 4 cycles''' |
− | | | + | </div></div><br> |
− | |[[Levels_of_Evidence#Efficacy| | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #3, 70/300/52.5, late RT {{#subobject:2140dc|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 17%"|Study | ||
+ | !style="width: 15%"|Dates of enrollment | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 17%"|Comparator | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1093/annonc/mdt140 Sun et al. 2013 (SMC 2003-02-016)] |
− | |style="background-color:# | + | |2003-2010 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
− | |style="background-color:# | + | |[[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]]; early RT |
+ | | style="background-color:#eeee01" |Non-inferior CR rate (primary endpoint) | ||
+ | | style="background-color:#91cf60" |Seems to have lower rates of neutropenic fever | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | + | ====Chemotherapy==== | |
− | + | *[[Cisplatin (Platinol)]] 70 mg/m<sup>2</sup> IV once on day 1 | |
− | === | + | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 |
− | + | ====Radiotherapy==== | |
− | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]], 210 cGy fractions x 25 fractions over 5 weeks, given during cycle 3 of chemotherapy (total dose: 5250 cGy) | |
− | == | + | '''21-day cycle for 4 cycles''' |
− | {| class="wikitable" style=" | + | </div></div><br> |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #4, 75/180/45, pre-planned dose reduction {{#subobject:2b9803|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 17%"|Study | ||
+ | !style="width: 15%"|Dates of enrollment | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 17%"|Comparator | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.1995.13.7.1632 Bunn et al. 1995] | ||
+ | |1989-1991 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]]; with GM-CSF support | ||
+ | | style="background-color:#ffffbf" |Did not meet secondary endpoints | ||
+ | | style="background-color:#1a9850" |Less toxic | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | ''Note: toxicity was the primary endpoint in this study.'' | |
− | < | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | + | ====Chemotherapy==== | |
− | ===Regimen # | + | *[[Cisplatin (Platinol)]] as follows: |
− | {| | + | **Cycles 1 to 3: 25 mg/m<sup>2</sup> IV once per day on days 1 to 3 |
− | | | + | **Cycles 4 to 6: 40 mg/m<sup>2</sup> IV once on day 1 |
− | |[[Levels_of_Evidence#Evidence| | + | *[[Etoposide (Vepesid)]] as follows: |
− | | | + | **Cycles 1 to 3: 60 mg/m<sup>2</sup> IV once per day on days 1 to 3 |
− | |[[Levels_of_Evidence# | + | **Cycles 4 to 6: 50 mg/m<sup>2</sup> IV once per day on days 1 to 3 |
+ | ====Radiotherapy==== | ||
+ | *Concurrent [[External_beam_radiotherapy|radiation therapy]] during cycles 1 & 2, 180 cGy fractions x 25 fractions (total dose: 4500 cGy) | ||
+ | '''21-day cycle for 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #5, 75/300/45 {{#subobject:7ed43e|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555437/ Faivre-Finn et al. 2017 (CONVERT)] |
− | |style="background-color:# | + | |2008-2013 |
− | |Cisplatin | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | |style="background-color:# | + | |[[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]]; once per day RT |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Cisplatin (Platinol)]] | + | ====Chemotherapy==== |
− | *[[Etoposide (Vepesid)]] | + | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 |
− | *Concurrent radiation therapy, | + | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 |
− | + | ====Radiotherapy==== | |
− | '''21-day cycle for 4 cycles''' | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]], 150 cGy fractions given twice per day x 30 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 4500 cGy) |
− | + | '''21-day cycle for 4 or 6 cycles''' | |
− | + | </div></div><br> | |
− | == | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | + | ===Regimen variant #6, 75/300/45, split doses of cisplatin {{#subobject:c54e7b|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | ===Regimen # | + | !style="width: 20%"|Study |
− | {| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Comparator |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555437/ Faivre-Finn et al. 2017 (CONVERT)] |
− | |style="background-color:# | + | |2008-2013 |
− | |Cisplatin | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | |style="background-color:# | + | |[[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]]; once per day RT |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Cisplatin (Platinol)]] | + | ====Chemotherapy==== |
+ | *[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | *Concurrent | + | ====Radiotherapy==== |
− | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]], 150 cGy fractions given twice per day x 30 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 4500 cGy) | |
− | ''' | + | '''21-day cycle for 4 or 6 cycles''' |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | = | + | ===Regimen variant #7, 75/700/42, partially oral etoposide {{#subobject:b5305|Variant=1}}=== |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 20%"|Study | |
− | ===Regimen # | + | !style="width: 20%"|Dates of enrollment |
− | {| | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | | | + | !style="width: 20%"|Comparator |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | | | ||
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2002.12.111 Sundstrøm et al. 2002] |
− | |style="background-color:# | + | |1989-1994 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
− | |style="background-color:# | + | |[[Small_cell_lung_cancer_-_historical#CEV_.26_RT|CEV & RT]] |
+ | | style="background-color:#1a9850" |Superior OS | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | ''Note: Oral etoposide to be taken on an empty stomach.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
− | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once on day 1 | + | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> PO once per day on days 2 to 4 |
− | *Concurrent thoracic radiation therapy, | + | ====Radiotherapy==== |
− | + | *Concurrent [[External_beam_radiotherapy|thoracic radiation therapy]], 280 cGy fractions once per day x 15 fractions (total dose: 4200 cGy) over 3 weeks, given "between the third and fourth chemotherapy courses" | |
− | ====Supportive | + | ====Supportive therapy==== |
*"Standard prehydration and posthydration procedures were followed in conjunction with cisplatin administration." | *"Standard prehydration and posthydration procedures were followed in conjunction with cisplatin administration." | ||
− | |||
'''21-day cycle for up to 5 cycles''' | '''21-day cycle for up to 5 cycles''' | ||
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | + | ====Subsequent treatment==== | |
− | ==== | + | *Sundstrøm et al. 2002, patients with CR: Prophylactic [[#Whole_brain_irradiation|cranial irradiation]] |
− | * | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ===Regimen # | + | ===Regimen variant #8, 80/240/50 {{#subobject:d203ec|Variant=1}}=== |
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Dates of enrollment |
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1097/01.coc.0000139940.52625.d0 McClay et al. 2005 (CALGB 9235)] |
− | |style="background-color:# | + | |1993-1999 |
+ | | style="background-color:#1a9851" |Phase 3 (E-de-esc) | ||
+ | |[[Stub#EP.2C_Tamoxifen.2C_RT|EP, Tamoxifen, RT]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Cisplatin (Platinol)]] | + | ====Chemotherapy==== |
− | *[[Etoposide (Vepesid)]] | + | *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1 |
− | * | + | *[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV once per day on days 1 to 3 |
− | + | ====Radiotherapy==== | |
− | + | *Concurrent [[External_beam_radiotherapy|thoracic radiation therapy]], 200 cGy fractions once per day x 25 fractions (total dose: 5000 cGy) over 5 weeks, started on cycle 4 day 1 of chemotherapy | |
− | + | '''21-day cycle for 5 cycles''' | |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #9, 80/300/45, 1 cycle of chemo {{#subobject:6426d9|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" | |
− | + | !style="width: 33%"|Study | |
− | '''21 | + | !style="width: 33%"|Dates of enrollment |
− | + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | === | + | |- |
− | # | + | |[https://doi.org/10.1200/jco.2006.07.1605 Saito et al. 2006 (WJTOG 9902)] |
− | + | |2000-2002 | |
− | + | | style="background-color:#91cf61" |Phase 2 | |
− | + | |- | |
− | + | |[https://doi.org/10.1016/s1470-2045(13)70511-4 Kubota et al. 2013 (JCOG0202)] | |
− | + | |2002-2006 | |
− | + | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | |
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | + | ====Chemotherapy==== | |
− | < | + | *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1 |
− | + | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | |
− | ===Regimen {{#subobject: | + | ====Radiotherapy==== |
− | {| | + | *Concurrent [[External_beam_radiotherapy|thoracic radiation therapy]], 150 cGy fractions given twice per day (at least 4, but preferably 6 hours between fractions) x 30 fractions (total dose: 4500 cGy) over 3 weeks, started on cycle 1 day 2 of chemotherapy |
− | | | + | '''28-day course''' |
− | |[[Levels_of_Evidence#Evidence| | + | </div> |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *WJTOG 9902: [[#Cisplatin_.26_Irinotecan_.28IC.29|IP]] consolidation | ||
+ | *JCOG0202: EP x 3 versus [[#Cisplatin_.26_Irinotecan_.28IC.29|IP]] consolidation | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #10, 80/300/45, 4 cycles of chemo {{#subobject:77843f|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2002.12.071 Takada et al. 2002 (JCOG 9104)] |
− | |style="background-color:# | + | |1991-1995 |
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
+ | |[[#Cisplatin_.26_Etoposide_.28EP.29|EP]], then [[#Radiation_therapy|RT]] | ||
+ | | style="background-color:#d9ef8b" |Might have superior OS | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | *Concurrent thoracic radiation therapy, | + | ====Radiotherapy==== |
+ | *Concurrent [[External_beam_radiotherapy|thoracic radiation therapy]], 150 cGy fractions given twice per day (4 or more hours between fractions) x 30 fractions (total dose: 4500 cGy) over 3 weeks, started on cycle 1 day 2 of chemotherapy | ||
+ | '''28-day cycle for 4 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *JCOG 9104, patients with CR or near-CR ("a scar-like shadow on chest films but no positive cytology and/or bronchoscopic biopsy"): Prophylactic [[#Whole_brain_irradiation|cranial irradiation]] | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #11, 90/300/39.9 {{#subobject:71c93e|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1093/annonc/mdn354 Sculier et al. 2008] | ||
+ | |1993-2006 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
+ | |[[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]]; daily cisplatin | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 90 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | ====Radiotherapy==== | ||
+ | *Concurrent [[External_beam_radiotherapy|radiation therapy]], 266 cGy fractions once per day x 15 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 3990 cGy) | ||
+ | '''21-day cycle for up to 6 cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Bunn PA Jr, Crowley J, Kelly K, Hazuka MB, Beasley K, Upchurch C, Livingston R; [[Study_Groups#SWOG|SWOG]]. Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group. J Clin Oncol. 1995 Jul;13(7):1632-41. Erratum in: J Clin Oncol 1995 Nov;13(11):2860. [https://doi.org/10.1200/JCO.1995.13.7.1632 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/7602352/ PubMed] | ||
+ | # '''Intergroup 0096:''' Turrisi AT 3rd, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, Wagner H, Aisner S, Johnson DH. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999 Jan 28;340(4):265-71. [https://doi.org/10.1056/NEJM199901283400403 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9920950/ PubMed] | ||
+ | # '''JCOG 9104:''' Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, Nishiwaki Y, Watanabe K, Noda K, Tamura T, Fukuda H, Saijo N. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol. 2002 Jul 15;20(14):3054-60. [https://doi.org/10.1200/jco.2002.12.071 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12118018/ PubMed] content property of [https://hemonc.org HemOnc.org] | ||
+ | # Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. [https://doi.org/10.1200/jco.2002.12.111 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12488411/ PubMed] | ||
+ | #Schild SE, Bonner JA, Shanahan TG, Brooks BJ, Marks RS, Geyer SM, Hillman SL, Farr GH Jr, Tazelaar HD, Krook JE, Geoffroy FJ, Salim M, Arusell RM, Mailliard JA, Schaefer PL, Jett JR. Long-term results of a phase III trial comparing once-daily radiotherapy with twice-daily radiotherapy in limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2004 Jul 15;59(4):943-51. [https://doi.org/10.1016/j.ijrobp.2004.01.055 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15234027/ PubMed] | ||
+ | # '''CALGB 9235:''' McClay EF, Bogart J, Herndon JE 2nd, Watson D, Evans L, Seagren SL, Green MR; [[Study_Groups#CALGB|CALGB]]. A phase III trial evaluating the combination of cisplatin, etoposide, and radiation therapy with or without tamoxifen in patients with limited-stage small cell lung cancer: Cancer and Leukemia Group B Study (9235). Am J Clin Oncol. 2005 Feb;28(1):81-90. [https://doi.org/10.1097/01.coc.0000139940.52625.d0 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15685040/ PubMed] | ||
+ | # '''WJTOG 9902:''' Saito H, Takada Y, Ichinose Y, Eguchi K, Kudoh S, Matsui K, Nakagawa K, Takada M, Negoro S, Tamura K, Ando M, Tada T, Fukuoka M; West Japan Thoracic Oncology Group. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902. J Clin Oncol. 2006 Nov 20;24(33):5247-52. [https://doi.org/10.1200/jco.2006.07.1605 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17114657/ PubMed] | ||
+ | # Sculier JP, Lafitte JJ, Efremidis A, Florin MC, Lecomte J, Berchier MC, Richez M, Berghmans T, Scherpereel A, Meert AP, Koumakis G, Leclercq N, Paesmans M, Van Houtte P; European Lung Cancer Working Party. A phase III randomised study of concomitant induction radiochemotherapy testing two modalities of radiosensitisation by cisplatin (standard versus daily) for limited small-cell lung cancer. Ann Oncol. 2008 Oct;19(10):1691-7. Epub 2008 May 25. [https://doi.org/10.1093/annonc/mdn354 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18504252/ PubMed] | ||
+ | # '''SMC 2003-02-016:''' Sun JM, Ahn YC, Choi EK, Ahn MJ, Ahn JS, Lee SH, Lee DH, Pyo H, Song SY, Jung SH, Jo JS, Jo J, Sohn HJ, Suh C, Lee JS, Kim SW, Park K. Phase III trial of concurrent thoracic radiotherapy with either first- or third-cycle chemotherapy for limited-disease small-cell lung cancer. Ann Oncol. 2013 Aug;24(8):2088-92. Epub 2013 Apr 16. Erratum in: Ann Oncol. 2014 Aug;25(8):1672. [https://doi.org/10.1093/annonc/mdt140 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23592701/ PubMed] [https://clinicaltrials.gov/study/NCT01125995 NCT01125995] | ||
+ | # '''JCOG0202:''' Kubota K, Hida T, Ishikura S, Mizusawa J, Nishio M, Kawahara M, Yokoyama A, Imamura F, Takeda K, Negoro S, Harada M, Okamoto H, Yamamoto N, Shinkai T, Sakai H, Matsui K, Nakagawa K, Shibata T, Saijo N, Tamura T; [[Study_Groups#JCOG|JCOG]]. Etoposide and cisplatin versus irinotecan and cisplatin in patients with limited-stage small-cell lung cancer treated with etoposide and cisplatin plus concurrent accelerated hyperfractionated thoracic radiotherapy (JCOG0202): a randomised phase 3 study. Lancet Oncol. 2014 Jan;15(1):106-13. Epub 2013 Dec 3. [https://doi.org/10.1016/s1470-2045(13)70511-4 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24309370/ PubMed] [https://clinicaltrials.gov/study/NCT00144989 NCT00144989] | ||
+ | # '''CONVERT:''' Faivre-Finn C, Snee M, Ashcroft L, Appel W, Barlesi F, Bhatnagar A, Bezjak A, Cardenal F, Fournel P, Harden S, Le Pechoux C, McMenemin R, Mohammed N, O'Brien M, Pantarotto J, Surmont V, Van Meerbeeck JP, Woll PJ, Lorigan P, Blackhall F; CONVERT Study Team. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol. 2017 Aug;18(8):1116-1125. Epub 2017 Jun 20. [https://doi.org/10.1016/s1470-2045(17)30318-2 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555437/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28642008/ PubMed] [https://clinicaltrials.gov/study/NCT00433563 NCT00433563] | ||
+ | #'''CALGB 30610:''' [https://clinicaltrials.gov/study/NCT00632853 NCT00632853] | ||
− | ''' | + | =Limited stage, adjuvant therapy= |
− | + | ==Cisplatin & Etoposide (EP) {{#subobject:ughacc|Regimen=1}}== | |
− | ==== | + | EP: '''<u>E</u>'''toposide & '''<u>P</u>'''latinol (Cisplatin) |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:18ytia|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.20.01806 Kenmotsu et al. 2020 (JCOG1205/1206)] | ||
+ | |2013-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cisplatin_.26_Irinotecan_.28IC.29_999|Cisplatin & Irinotecan]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of RFS<br>RFS36: 65.4% vs 69%<br>(HR 0.93, 95% CI 0.58-1.50) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Lung_cancer_surgery|Complete surgical resection]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | '''21-day cycle for up to 4 cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''JCOG1205/1206:''' Kenmotsu H, Niho S, Tsuboi M, Wakabayashi M, Ishii G, Nakagawa K, Daga H, Tanaka H, Saito H, Aokage K, Takahashi T, Menju T, Kasai T, Yoshino I, Minato K, Okada M, Eba J, Asamura H, Ohe Y, Watanabe SI. Randomized Phase III Study of Irinotecan Plus Cisplatin Versus Etoposide Plus Cisplatin for Completely Resected High-Grade Neuroendocrine Carcinoma of the Lung: JCOG1205/1206. J Clin Oncol. 2020 Dec 20;38(36):4292-4301. Epub 2020 Nov 2. [https://doi.org/10.1200/jco.20.01806 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33136471/ PubMed] UMIN000010298 | ||
+ | =Limited stage, consolidation after upfront therapy= | ||
+ | ==Cisplatin & Irinotecan (IC) {{#subobject:fe9413|Regimen=1}}== | ||
+ | IP: '''<u>I</u>'''rinotecan, '''<u>P</u>'''latinol (Cisplatin) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:540b9f|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2006.07.1605 Saito et al. 2006 (WJTOG 9902)] | ||
+ | |2000-2002 | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *Definitive [[#Cisplatin.2C_Etoposide.2C_RT|Cisplatin, Etoposide, RT]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Irinotecan (Camptosar)]] 60 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | *[[Irinotecan (Camptosar)]] 60 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
+ | ====Supportive therapy==== | ||
+ | *[[:Category:Granulocyte colony-stimulating factors|G-CSF]] (no additional details given) starting after day 4 | ||
+ | '''28-day cycle for 3 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *WJTOG 9902, patients with CR or good PR: Prophylactic [[#Whole_brain_irradiation|cranial irradiation]] | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''WJTOG 9902:''' Saito H, Takada Y, Ichinose Y, Eguchi K, Kudoh S, Matsui K, Nakagawa K, Takada M, Negoro S, Tamura K, Ando M, Tada T, Fukuoka M; West Japan Thoracic Oncology Group. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902. J Clin Oncol. 2006 Nov 20;24(33):5247-52. [https://doi.org/10.1200/jco.2006.07.1605 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17114657/ PubMed] | ||
+ | ==Radiation therapy {{#subobject:508a85|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:c48aca|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.1985.3.11.1471 Evans et al. 1985] | ||
+ | |1981-1984 | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *Induction [[#Cisplatin_.26_Etoposide_.28EP.29|EP]] x 6 | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Radiotherapy==== | ||
+ | *"Patients who did not have evidence of tumor spread beyond the mediastinum and/or ipsilateral supraclavicular notes" received [[External beam radiotherapy|thoracic radiation]] in 250 cGy fractions x 10 fractions (total dose: 2500 cGy) | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. [https://doi.org/10.1200/jco.1985.3.11.1471 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2997406/ PubMed] | ||
+ | # '''LLCG-STUDY-12:''' Lee SM, Woll PJ, Rudd R, Ferry D, O'Brien M, Middleton G, Spiro S, James L, Ali K, Jitlal M, Hackshaw A. Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2009 Aug 5;101(15):1049-57. Epub 2009 Jul 16. [https://doi.org/10.1093/jnci/djp200 link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/19608997/ PubMed] [https://clinicaltrials.gov/study/NCT00061919 NCT00061919] | ||
+ | ==Whole brain irradiation {{#subobject:49c1e3|Regimen=1}}== | ||
+ | PCI: '''<u>P</u>'''rophylactic '''<u>C</u>'''ranial '''<u>I</u>'''rradiation | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, 2000 cGy {{#subobject:900486|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1001/jama.1981.03310300023013 Cox et al. 1981] | ||
+ | |1975-1978 | ||
+ | | style="background-color:#91cf61" |Non-randomized | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.1985.3.11.1471 Evans et al. 1985] | ||
+ | |1981-1984 | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | |- | ||
+ | |[https://doi.org/10.1023/a:1012295131640 Skarlos et al. 2001] | ||
+ | |1993-1999 | ||
+ | | style="background-color:#91cf61" |Non-randomized part of phase 2 RCT | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: in Evans et al. 1985, the WB-XRT is given in-between cycles 3 & 4.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *Evans et al. 1985: Induction [[#Cisplatin_.26_Etoposide_.28EP.29|EP]] x 3 | ||
+ | *Skarlos et al. 2001: Definitive [[#Carboplatin.2C_Etoposide.2C_RT|EP & early HTRT]] versus [[#Carboplatin.2C_Etoposide.2C_RT|EP & late HTRT]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Radiotherapy==== | ||
+ | *[[External beam radiotherapy|Whole brain irradiation]], 400 cGy fractions once per day x 5 fractions (total dose: 2000 cGy) | ||
+ | '''1-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *Evans et al. 1985: [[#Cisplatin_.26_Etoposide_.28EP.29|EP]] consolidation x 3 | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 2400 cGy {{#subobject:5b88f0|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2002.12.071 Takada et al. 2002 (JCOG 9104)] | ||
+ | |1991-1995 | ||
+ | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *Definitive [[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]] versus [[#Cisplatin_.26_Etoposide_.28EP.29|EP]] induction followed by definitive [[#Radiation_therapy|RT]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
− | ==== | + | ====Radiotherapy==== |
− | *[[ | + | *[[External beam radiotherapy|Whole brain irradiation]], 150 cGy fractions given twice per day x 16 fractions (total dose: 2400 cGy) |
− | + | '''2-week course''' | |
− | ''' | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | === | + | ===Regimen variant #3, 2500 cGy {{#subobject:1475db|Variant=1}}=== |
− | '' | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | + | !style="width: 20%"|Study | |
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/NEJM199901283400403 Turrisi et al. 1999 (Intergroup 0096)] | ||
+ | |1989-1992 | ||
+ | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S1470-2045(09)70101-9 Le Péchoux et al. 2009 (PCI 99-01/EORTC 22003-08004/RTOG 0212/IFCT 99-01)] | ||
+ | |1999-2005 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Whole_brain_irradiation|PCI]] x 36 Gy | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of incidence of brain metastases at 2 years | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2006.07.1605 Saito et al. 2006 (WJTOG 9902)] | ||
+ | |2000-2002 | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *Intergroup 0096: Definitive [[#Cisplatin.2C_Etoposide.2C_RT|EP & once-daily RT]] versus [[#Cisplatin.2C_Etoposide.2C_RT|EP & twice-daily RT]] | ||
+ | *WJTOG 9902: Definitive [[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]], then [[#Cisplatin_.26_Irinotecan_.28IC.29|IP]] consolidation x 3 | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Radiotherapy==== | ||
+ | *[[External beam radiotherapy|Whole brain irradiation]], 250 cGy fractions x 10 fractions (total dose: 2500 cGy) | ||
+ | '''2-week course''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #4, 3000 cGy {{#subobject:63970e|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2002.12.111 Sundstrøm et al. 2002] | ||
+ | |1989-1994 | ||
+ | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *Definitive [[Small_cell_lung_cancer_-_historical#CEV_.26_RT|CEV & RT]] versus [[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Radiotherapy==== | ||
+ | *[[External beam radiotherapy|Whole brain irradiation]], 200 cGy fractions once per day x 15 fractions (total dose: 3000 cGy) | ||
+ | '''3-week course''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Cox JD, Stanley K, Petrovich Z, Paig C, Yesner R. Cranial irradiation in cancer of the lung of all cell types. JAMA. 1981 Feb 6;245(5):469-72. [https://doi.org/10.1001/jama.1981.03310300023013 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7452872/ PubMed] | ||
+ | # Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. [https://doi.org/10.1200/jco.1985.3.11.1471 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2997406/ PubMed] | ||
+ | # '''Intergroup 0096:''' Turrisi AT 3rd, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, Wagner H, Aisner S, Johnson DH. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999 Jan 28;340(4):265-71. [https://doi.org/10.1056/NEJM199901283400403 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9920950/ PubMed] | ||
+ | # '''Meta-analysis:''' Aupérin A, Arriagada R, Pignon JP, Le Péchoux C, Gregor A, Stephens RJ, Kristjansen PE, Johnson BE, Ueoka H, Wagner H, Aisner J; Prophylactic Cranial Irradiation Overview Collaborative Group. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med. 1999 Aug 12;341(7):476-84. [https://doi.org/10.1056/NEJM199908123410703 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10441603/ PubMed] | ||
+ | # '''JCOG 9104:''' Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, Nishiwaki Y, Watanabe K, Noda K, Tamura T, Fukuda H, Saijo N. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol. 2002 Jul 15;20(14):3054-60. [https://doi.org/10.1200/jco.2002.12.071 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12118018/ PubMed] content property of [https://hemonc.org HemOnc.org] | ||
+ | # Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. [https://doi.org/10.1200/jco.2002.12.111 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12488411/ PubMed] | ||
+ | # '''WJTOG 9902:''' Saito H, Takada Y, Ichinose Y, Eguchi K, Kudoh S, Matsui K, Nakagawa K, Takada M, Negoro S, Tamura K, Ando M, Tada T, Fukuoka M; West Japan Thoracic Oncology Group. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902. J Clin Oncol. 2006 Nov 20;24(33):5247-52. [https://doi.org/10.1200/jco.2006.07.1605 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17114657/ PubMed] | ||
+ | # '''PCI 99-01/EORTC 22003-08004/RTOG 0212/IFCT 99-01:''' Le Péchoux C, Dunant A, Senan S, Wolfson A, Quoix E, Faivre-Finn C, Ciuleanu T, Arriagada R, Jones R, Wanders R, Lerouge D, Laplanche A; Prophylactic Cranial Irradiation (PCI) Collaborative Group. Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212, and IFCT 99-01): a randomised clinical trial. Lancet Oncol. 2009 May;10(5):467-74. Epub 2009 Apr 20. [https://doi.org/10.1016/S1470-2045(09)70101-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19386548/ PubMed] [https://clinicaltrials.gov/study/NCT00005062 NCT00005062] | ||
+ | =Extensive stage, induction= | ||
+ | ==Belotecan & Cisplatin {{#subobject:9fbf31|Regimen=1}}== | ||
+ | BP: '''<u>B</u>'''elotecan and '''<u>P</u>'''latinol (Cisplatin) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:949381|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002146/ Oh et al. 2016 (COMBAT)] | ||
+ | |2009-2013 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
+ | |[[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]; 60/100 | ||
+ | | style="background-color:#eeee01" |Non-inferior RR (primary endpoint) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: the total number of planned cycles is not described in the manuscript; total duration information here was provided by the authors.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Belotecan (Camptobell)]] 0.5 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 4 | ||
+ | *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | '''21-day cycle for 4 to 8 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # '''COMBAT:''' Oh IJ, Kim KS, Park CK, Kim YC, Lee KH, Jeong JH, Kim SY, Lee JE, Shin KC, Jang TW, Lee HK, Lee KY, Lee SY. Belotecan/cisplatin versus etoposide/cisplatin in previously untreated patients with extensive-stage small cell lung carcinoma: a multi-center randomized phase III trial. BMC Cancer. 2016 Aug 26;16:690. [https://doi.org/10.1186/s12885-016-2741-z link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002146/ link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27566413/ PubMed] [https://clinicaltrials.gov/study/NCT00826644 NCT00826644] |
− | + | ==Carboplatin & Etoposide (CE) {{#subobject:de3ba6|Regimen=1}}== | |
− | + | CE: '''<u>C</u>'''arboplatin & '''<u>E</u>'''toposide | |
− | ==Carboplatin & Etoposide ( | + | <br>EP: '''<u>E</u>'''toposide & '''<u>P</u>'''araplatin (Carboplatin) |
− | {| class="wikitable" style=" | + | <br>EC: '''<u>E</u>'''toposide & '''<u>C</u>'''arboplatin |
+ | <br>Ca/E: '''<u>Ca</u>'''rboplatin & '''<u>E</u>'''toposide | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, AUC 4/600, PO etoposide {{#subobject:8ac097|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2007.15.7545 Hermes et al. 2008] | ||
+ | |2001-2005 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Carboplatin_.26_Irinotecan|Carboplatin & Irinotecan]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ===Regimen # | + | ====Chemotherapy==== |
− | {| | + | *[[Carboplatin (Paraplatin)]] AUC 4 (Chatelut formula) IV once on day 1 |
− | | | + | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> PO once per day on days 1 to 5 |
− | |[[Levels_of_Evidence#Evidence| | + | '''21-day cycle for 4 cycles''' |
− | | | + | </div></div><br> |
− | |[[Levels_of_Evidence# | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #2, AUC 5/240 {{#subobject:471848|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360311/ Okamoto et al. 2007 (JCOG 9702)] |
− | |style="background-color:# | + | |1998-2004 |
− | | | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
− | |style="background-color:# | + | |[[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]; split-dose |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.cllc.2013.11.006 Sekine et al. 2013 (D0702002)] |
− | |style="background-color:# | + | |2006-07-04 to 2007-09-05 |
− | |[[# | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#Amrubicin_monotherapy_999|Amrubicin]] |
+ | | style="background-color:#ffffbf" |Inconclusive whether non-inferior OS (primary endpoint) | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1 | *[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1 | ||
− | *[[Etoposide (Vepesid)]] | + | *[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV once per day on days 1 to 3 |
+ | ====Supportive therapy==== | ||
+ | *JCOG 9702: [[:Category:Granulocyte colony-stimulating factors|G-CSF]] | ||
+ | '''21-day cycle for varying durations: 4 cycles (JCOG 9702); 4 to 6 cycles (D0702002)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | ==== | + | ===Regimen variant #3, AUC 5/300, 21-day cycles {{#subobject:1eba05|Variant=1}}=== |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 20%"|Study | |
− | + | !style="width: 20%"|Dates of enrollment | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | === | + | !style="width: 20%"|Comparator |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
− | | | + | |- |
− | |[[ | + | |[https://doi.org/10.1200/jco.2009.23.1548 Socinski et al. 2009 (JMHO)] |
− | | | + | |2006-08 to 2007-12 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
+ | |[[#Carboplatin_.26_Pemetrexed_999|Carboplatin & Pemetrexed]] | ||
+ | | style="background-color:#1a9850" |Superior OS<sup>1</sup> (primary endpoint)<br>Median OS: 10.6 vs 8.1 mo<br>(HR 0.64, 95% CI 0.52-0.79) | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2010.29.3423 Spigel et al. 2011 (SALUTE)] | ||
+ | |2007-2008 | ||
+ | | style="background-color:#1a9851" |Randomized Phase 2 (C) | ||
+ | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Bevacizumab|CE & Bevacizumab]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Bevacizumab|EP & Bevacizumab]] | ||
+ | | style="background-color:#fc8d59" |Seems to have inferior PFS | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429175/ Ready et al. 2015 (CALGB 30504)] | ||
+ | |2007-2011 | ||
+ | | style="background-color:#91cf61" |Non-randomized part of phase 2 RCT | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2016.67.6601 Reck et al. 2016 (CA184-156)] | ||
+ | |2012-2014 | ||
+ | |style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[Stub#Carboplatin_.26_Etoposide_.28CE.29_.26_Ipilimumab|CE & Ipilimumab]]<br>1b. [[Stub#EP_.26_Ipilimumab|EP & Ipilimumab]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 10.9 vs 11 mo<br>(HR 1.06, 95% CI 0.92-1.23) | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2016.71.7454 Jalal et al. 2017 (MATISSE)] | ||
+ | |2012-2013 | ||
+ | | style="background-color:#1a9851" |Randomized Phase 2 (C) | ||
+ | |[[#PaCE_999|PaCE]] | ||
+ | | style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: 10.37 vs 10.03 mo<br>(HR 0.77, 95% CI 0.56-1.05) | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/NEJMoa1809064 Horn et al. 2018 (IMpower133)] | ||
+ | |2016-06-06 to 2017-05-31 | ||
+ | |style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Carboplatin_.26_Etoposide_.28CE.29_.26_Atezolizumab|CE & Atezolizumab]] | ||
+ | | style="background-color:#fc8d59" |Seems to have inferior OS<sup>2</sup> | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S0140-6736(19)32222-6 Paz-Ares et al. 2019 (CASPIAN)] | ||
+ | |2017-03-27 to 2018-05-29 | ||
+ | |style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Durvalumab|CE & Durvalumab]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Durvalumab|EP & Durvalumab]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ Rudin et al. 2020 (KEYNOTE-604)] | ||
+ | |2017-05-15 to 2018-07-30 | ||
+ | |style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[Small_cell_lung_cancer_-_historical#Carboplatin_.26_Etoposide_.28CE.29_.26_Pembrolizumab|CE & Pembrolizumab]]<br>1b. [[Small_cell_lung_cancer_-_historical#Cisplatin_.26_Etoposide_.28EP.29_.26_Pembrolizumab|EP & Pembrolizumab]] | ||
+ | | style="background-color:#fc8d59" |Seems to have inferior OS | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s1470-2045(22)00224-8 Wang et al. 2022 (CAPSTONE-1)] | ||
+ | |2018-2020 | ||
+ | |style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Carboplatin_.26_Etoposide_.28CE.29_.26_Adebrelimab_777|CE & Adebrelimab]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.jtho.2024.03.008 Cheng et al. 2024 (RATIONALE-312)] |
− | |style="background-color:# | + | |2019-07-22 to 2021-04-21 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Tislelizumab|CE & Tislelizumab]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Tislelizumab|EP & Tislelizumab]] |
+ | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>JMHO was designed as a non-inferiority trial; however, the control arm was found to be statistically superior for the primary endpoint of OS.''<br> | ||
+ | ''<sup>2</sup>Reported efficacy for IMpower133 is based on the 2020 update.''<br> | ||
+ | ''Note: CASPIAN gave a range of dosing; see paper for details.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Carboplatin (Paraplatin)]] AUC 5 | + | *[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1 |
− | *[[Etoposide (Vepesid)]] | + | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 |
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *Socinksi et al. 2009: "supportive therapies, such as erythropoietic agents or granulocyte colony-stimulating factors, were administered according to the American Society of Clinical Oncology guidelines" |
− | * | + | '''21-day cycle for varying durations: 4 cycles (CASPIAN, RATIONALE-312); 4 to 6 cycles''' |
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | '''21-day cycle for | + | ====Subsequent treatment==== |
− | + | *CALGB 30504, SD or better: [[Small_cell_lung_cancer_-_null_regimens#Observation_2|Observation]] versus [[#Sunitinib_monotherapy|sunitinib]] maintenance | |
− | ===Regimen # | + | </div></div><br> |
− | {| | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | | | + | ===Regimen variant #4, AUC 5/300, 28-day cycles {{#subobject:d904aa|Variant=1}}=== |
− | |[[Levels_of_Evidence#Evidence| | + | {| class="wikitable" style="width: 60%; text-align:center;" |
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.1999.17.11.3540 Okamoto et al. 1999] |
− | |style="background-color:# | + | |1995-1996 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1023/a:1011171722175 Quoix et al. 2001] |
− | |style="background-color:# | + | |1997-1999 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
+ | ====Eligibility criteria==== | ||
+ | *At least 70 years old | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 1, '''given first''' | *[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 1, '''given first''' | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 3, '''given second''' | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 3, '''given second''' | ||
+ | ====Supportive therapy==== | ||
+ | *[[Dexamethasone (Decadron)]] 8 mg IV once per day on days 1 to 3, prior to chemotherapy | ||
+ | *[[Granisetron]] 40 mcg/kg IV once per day on days 1 to 3, prior to chemotherapy | ||
+ | *Okamoto et al. 1999: [[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 2 mcg/kg SC given for grade 3 or greater leukopenia/neutropenia | ||
+ | *Quiox et al. 2001: "Haematopoietic growth factors were allowed as prophylactic or curative treatment only if grade 4 neutropenia greater than 7 days occurred" | ||
+ | '''28-day cycle for varying durations: 4 cycles (Okamoto et al. 1999); 6 cycles (Quoix et al. 2001)''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
*Palliative radiation therapy was allowed to control persistent pain from bony metastases | *Palliative radiation therapy was allowed to control persistent pain from bony metastases | ||
− | + | </div></div><br> | |
− | ==== | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | *[[ | + | ===Regimen variant #5, AUC 5/360 {{#subobject:927150|Variant=1}}=== |
− | *[[ | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | * | + | !style="width: 20%"|Study |
− | * | + | !style="width: 20%"|Dates of enrollment |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | ''' | + | !style="width: 20%"|Comparator |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ Seckl et al. 2017 (LUNGSTAR)] | ||
+ | |2007-2012 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_999|CE & Pravastatin]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_999|EP & Pravastatin]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>OS24: 14.1% vs 13.2%<br>(HR 0.99, 95% CI 0.86-1.14) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | '''21-day cycle for 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #6, AUC 5/420 {{#subobject:69fffb|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1097/coc.0b013e31817be954 Heigener et al. 2009] | ||
+ | |2000-2003 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]; dose-intense | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
+ | |- | ||
+ | |[https://doi.org/10.1093/annonc/mdj137 Schmittel et al. 2006] | ||
+ | |2002-2008 | ||
+ | | style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic) | ||
+ | |[[#Carboplatin_.26_Irinotecan|IP]] | ||
+ | | style="background-color:#fee08b" |Might have inferior OS (secondary endpoint) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 140 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 to 3 | ||
+ | ====Supportive therapy==== | ||
+ | *[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]] IV once per day on days 1 to 3, prior to chemotherapy | ||
+ | *[[Loperamide (Imodium)]] 4 mg PO prn first episode of diarrhea, then 2 mg PO Q2H until diarrhea stops | ||
+ | '''21- to 28-day cycle for up to 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #7, AUC 5/440, 1 day of oral etoposide per cycle {{#subobject:47c27e|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1093/jnci/djp200 Lee et al. 2009 (LLCG-STUDY-12)] | ||
+ | |2003-2006 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[Stub#Carboplatin_.26_Etoposide_.28CE.29_.26_Thalidomide|CE & Thalidomide]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 10.5 vs 10.1 mo<br>(HR 0.92, 95% CI 0.79-1.08) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ Seckl et al. 2017 (LUNGSTAR)] | ||
+ | |2007-2012 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_999|CE & Pravastatin]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_999|EP & Pravastatin]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>OS24: 14.1% vs 13.2%<br>(HR 0.99, 95% CI 0.86-1.14) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2, then 100 mg PO twice per day on day 3 | ||
+ | '''21-day cycle for up to 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #8, AUC 5/520, 2 days of oral etoposide per cycle {{#subobject:ae04e8|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1093/jnci/djp200 Lee et al. 2009 (LLCG-STUDY-12)] | ||
+ | |2003-2006 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[Stub#Carboplatin_.26_Etoposide_.28CE.29_.26_Thalidomide|CE & Thalidomide]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 10.5 vs 10.1 mo<br>(HR 0.92, 95% CI 0.79-1.08) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ Seckl et al. 2017 (LUNGSTAR)] | ||
+ | |2007-2012 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_999|CE & Pravastatin]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_999|EP & Pravastatin]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>OS24: 14.1% vs 13.2%<br>(HR 0.99, 95% CI 0.86-1.14) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once on day 1, then 100 mg PO twice per day on days 2 & 3 | ||
+ | '''21-day cycle for up to 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #9, AUC 6/360 {{#subobject:92cv50|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ Seckl et al. 2017 (LUNGSTAR)] | ||
+ | |2007-2012 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_999|CE & Pravastatin]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_999|EP & Pravastatin]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>OS24: 14.1% vs 13.2%<br>(HR 0.99, 95% CI 0.86-1.14) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | '''21-day cycle for 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #10, AUC 6/440, 1 day of oral etoposide per cycle {{#subobject:acc27e|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ Seckl et al. 2017 (LUNGSTAR)] | ||
+ | |2007-2012 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_999|CE & Pravastatin]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_999|EP & Pravastatin]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>OS24: 14.1% vs 13.2%<br>(HR 0.99, 95% CI 0.86-1.14) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2, then 100 mg PO twice per day on day 3 | ||
+ | '''21-day cycle for up to 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #11, AUC 6/520, 2 days of oral etoposide per cycle {{#subobject:ae04y1|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ Seckl et al. 2017 (LUNGSTAR)] | ||
+ | |2007-2012 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_999|CE & Pravastatin]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_999|EP & Pravastatin]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>OS24: 14.1% vs 13.2%<br>(HR 0.99, 95% CI 0.86-1.14) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once on day 1, then 100 mg PO twice per day on days 2 & 3 | ||
+ | '''21-day cycle for up to 6 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Okamoto H, Watanabe K, Nishiwaki Y, Mori K, Kurita Y, Hayashi I, Masutani M, Nakata K, Tsuchiya S, Isobe H, Saijo N. Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer. J Clin Oncol. 1999 Nov;17(11):3540-5. [ | + | # Okamoto H, Watanabe K, Nishiwaki Y, Mori K, Kurita Y, Hayashi I, Masutani M, Nakata K, Tsuchiya S, Isobe H, Saijo N. Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer. J Clin Oncol. 1999 Nov;17(11):3540-5. [https://doi.org/10.1200/jco.1999.17.11.3540 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10550152/ PubMed] |
− | # Quoix E, Breton JL, Daniel C, Jacoulet P, Debieuvre D, Paillot N, Kessler R, Moreau L, Coëtmeur D, Lemarié E, Milleron B. Etoposide phosphate with carboplatin in the treatment of elderly patients with small-cell lung cancer: a phase II study. Ann Oncol. 2001 Jul;12(7):957-62. [ | + | # Quoix E, Breton JL, Daniel C, Jacoulet P, Debieuvre D, Paillot N, Kessler R, Moreau L, Coëtmeur D, Lemarié E, Milleron B. Etoposide phosphate with carboplatin in the treatment of elderly patients with small-cell lung cancer: a phase II study. Ann Oncol. 2001 Jul;12(7):957-62. [https://doi.org/10.1023/a:1011171722175 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11521802/ PubMed] |
− | # Schmittel A, Fischer von Weikersthal L, Sebastian M, Martus P, Schulze K, Hortig P, Reeb M, Thiel E, Keilholz U. A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer. Ann Oncol. 2006 Apr;17(4):663-7. Epub 2006 Jan 19. [ | + | # Schmittel A, Fischer von Weikersthal L, Sebastian M, Martus P, Schulze K, Hortig P, Reeb M, Thiel E, Keilholz U. A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer. Ann Oncol. 2006 Apr;17(4):663-7. Epub 2006 Jan 19. [https://doi.org/10.1093/annonc/mdj137 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16423848/ PubMed] |
− | ## '''Update:''' Schmittel A, Sebastian M, Fischer von Weikersthal L, Martus P, Gauler TC, Kaufmann C, Hortig P, Fischer JR, Link H, Binder D, Fischer B, Caca K, Eberhardt WE, Keilholz U; Arbeitsgemeinschaft Internistische Onkologie Thoracic Oncology Study Group. A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol. 2011 Aug;22(8):1798-804. Epub 2011 Jan 25. [ | + | ## '''Update:''' Schmittel A, Sebastian M, Fischer von Weikersthal L, Martus P, Gauler TC, Kaufmann C, Hortig P, Fischer JR, Link H, Binder D, Fischer B, Caca K, Eberhardt WE, Keilholz U; Arbeitsgemeinschaft Internistische Onkologie Thoracic Oncology Study Group. A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol. 2011 Aug;22(8):1798-804. Epub 2011 Jan 25. [https://doi.org/10.1093/annonc/mdq652 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21266516/ PubMed] |
+ | # '''JCOG 9702:''' Okamoto H, Watanabe K, Kunikane H, Yokoyama A, Kudoh S, Asakawa T, Shibata T, Kunitoh H, Tamura T, Saijo N. Randomised phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702. Br J Cancer. 2007 Jul 16;97(2):162-9. Epub 2007 Jun 19. [https://doi.org/10.1038/sj.bjc.6603810 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360311/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17579629/ PubMed] | ||
+ | # Hermes A, Bergman B, Bremnes R, Ek L, Fluge S, Sederholm C, Sundstrøm S, Thaning L, Vilsvik J, Aasebø U, Sörenson S. Irinotecan plus carboplatin versus oral etoposide plus carboplatin in extensive small-cell lung cancer: a randomized phase III trial. J Clin Oncol. 2008 Sep 10;26(26):4261-7. [https://doi.org/10.1200/JCO.2007.15.7545 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18779613/ PubMed] | ||
+ | # Heigener DF, Manegold C, Jäger E, Saal JG, Zuna I, Gatzemeier U. Multicenter randomized open-label phase III study comparing efficacy, safety, and tolerability of conventional carboplatin plus etoposide versus dose-intensified carboplatin plus etoposide plus lenograstim in small-cell lung cancer in "extensive disease" stage. Am J Clin Oncol. 2009 Feb;32(1):61-4. [https://doi.org/10.1097/coc.0b013e31817be954 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19194127/ PubMed] | ||
+ | # '''LLCG-STUDY-12:''' Lee SM, Woll PJ, Rudd R, Ferry D, O'Brien M, Middleton G, Spiro S, James L, Ali K, Jitlal M, Hackshaw A. Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2009 Aug 5;101(15):1049-57. Epub 2009 Jul 16. [https://doi.org/10.1093/jnci/djp200 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19608997/ PubMed] [https://clinicaltrials.gov/study/NCT00061919 NCT00061919] | ||
<!-- Presented in part as an oral presentation at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL, and the 8th Annual Targeted Therapies for the Treatment of Lung Cancer Meeting, February 20-23, 2008, Santa Monica, CA. --> | <!-- Presented in part as an oral presentation at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL, and the 8th Annual Targeted Therapies for the Treatment of Lung Cancer Meeting, February 20-23, 2008, Santa Monica, CA. --> | ||
− | # Socinski MA, Smit EF, Lorigan P, Konduri K, Reck M, Szczesna A, Blakely J, Serwatowski P, Karaseva NA, Ciuleanu T, Jassem J, Dediu M, Hong S, Visseren-Grul C, Hanauske AR, Obasaju CK, Guba SC, Thatcher N. Phase III study of pemetrexed plus carboplatin compared with etoposide plus carboplatin in chemotherapy-naive patients with extensive-stage small-cell lung cancer. J Clin Oncol. 2009 Oct 1;27(28):4787-92. Epub 2009 Aug 31. [ | + | # '''JMHO:''' Socinski MA, Smit EF, Lorigan P, Konduri K, Reck M, Szczesna A, Blakely J, Serwatowski P, Karaseva NA, Ciuleanu T, Jassem J, Dediu M, Hong S, Visseren-Grul C, Hanauske AR, Obasaju CK, Guba SC, Thatcher N. Phase III study of pemetrexed plus carboplatin compared with etoposide plus carboplatin in chemotherapy-naive patients with extensive-stage small-cell lung cancer. J Clin Oncol. 2009 Oct 1;27(28):4787-92. Epub 2009 Aug 31. [https://doi.org/10.1200/jco.2009.23.1548 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19720897/ PubMed] [https://clinicaltrials.gov/study/NCT00363415 NCT00363415] |
− | # Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. [ | + | # '''SALUTE:''' Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. [https://doi.org/10.1200/JCO.2010.29.3423 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21502556/ PubMed] [https://clinicaltrials.gov/study/NCT00403403 NCT00403403] |
+ | # '''D0702002:''' Sekine I, Okamoto H, Horai T, Nakagawa K, Ohmatsu H, Yokoyama A, Katakami N, Shibuya M, Saijo N, Fukuoka M. A randomized phase III study of single-agent amrubicin vs carboplatin/etoposide in elderly patients with extensive-disease small-cell lung cancer. Clin Lung Cancer. 2014 Mar;15(2):96-102. Epub 2013 Nov 14. [https://doi.org/10.1016/j.cllc.2013.11.006 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24361248/ PubMed] [https://clinicaltrials.gov/study/NCT00286169 NCT00286169] | ||
+ | # '''CALGB 30504:''' Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, Baggstrom M, Masters GA, Graziano SL, Crawford J, Bogart J, Vokes EE. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: A randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (Alliance). J Clin Oncol. 2015 May 20;33(15):1660-5. Epub 2015 Mar 2. [https://doi.org/10.1200/JCO.2014.57.3105 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429175/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25732163/ PubMed] [https://clinicaltrials.gov/study/NCT00453154 NCT00453154] | ||
+ | # '''CA184-156:''' Reck M, Luft A, Szczesna A, Havel L, Kim SW, Akerley W, Pietanza MC, Wu YL, Zielinski C, Thomas M, Felip E, Gold K, Horn L, Aerts J, Nakagawa K, Lorigan P, Pieters A, Kong Sanchez T, Fairchild J, Spigel D. Phase III randomized trial of ipilimumab plus etoposide and platinum versus placebo plus etoposide and platinum in extensive-stage small-cell lung cancer. J Clin Oncol. 2016 Nov 1;34(31):3740-3748. [https://doi.org/10.1200/JCO.2016.67.6601 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27458307/ PubMed] [https://clinicaltrials.gov/study/NCT01450761 NCT01450761] | ||
+ | # '''LUNGSTAR:''' Seckl MJ, Ottensmeier CH, Cullen M, Schmid P, Ngai Y, Muthukumar D, Thompson J, Harden S, Middleton G, Fife KM, Crosse B, Taylor P, Nash S, Hackshaw A. Multicenter, phase III, randomized, double-blind, placebo-controlled trial of pravastatin added to first-line standard chemotherapy in small-cell lung cancer (LUNGSTAR). J Clin Oncol. 2017 May 10;35(14):1506-1514. Epub 2017 Feb 27. [https://doi.org/10.1200/JCO.2016.69.7391 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28240967/ PubMed] [https://clinicaltrials.gov/study/NCT00433498 NCT00433498] | ||
+ | # '''MATISSE:''' Jalal SI, Lavin P, Lo G, Lebel F, Einhorn L. Carboplatin and etoposide with or without palifosfamide in untreated extensive-stage small-cell lung cancer: A multicenter, adaptive, randomized phase III study (MATISSE). J Clin Oncol. 2017 Aug 10;35(23):2619-2623. Epub 2017 Jun 12. [https://doi.org/10.1200/JCO.2016.71.7454 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28605291/ PubMed] [https://clinicaltrials.gov/study/NCT01555710 NCT01555710] | ||
+ | # '''IMpower133:''' Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. Epub 2018 Sep 25. [https://doi.org/10.1056/NEJMoa1809064 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/30280641/ PubMed] [https://clinicaltrials.gov/study/NCT02763579 NCT02763579] | ||
+ | ##'''PRO analysis:''' Mansfield AS, Każarnowicz A, Karaseva N, Sánchez A, De Boer R, Andric Z, Reck M, Atagi S, Lee JS, Garassino M, Liu SV, Horn L, Wen X, Quach C, Yu W, Kabbinavar F, Lam S, Morris S, Califano R. Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. Ann Oncol. 2020 Feb;31(2):310-317. Epub 2019 Dec 9. [https://doi.org/10.1016/j.annonc.2019.10.021 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31959349/ PubMed] | ||
+ | ## '''Update:''' Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, Garassino MC, De Castro Carpeno J, Califano R, Nishio M, Orlandi F, Alatorre-Alexander J, Leal T, Cheng Y, Lee JS, Lam S, McCleland M, Deng Y, Phan S, Horn L. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021 Feb 20;39(6):619-630. Epub 2021 Jan 13. [https://doi.org/10.1200/jco.20.01055 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078320/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33439693/ PubMed] | ||
+ | # '''CASPIAN:''' Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. Epub 2019 Oct 4. [https://doi.org/10.1016/S0140-6736(19)32222-6 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31590988/ PubMed] [https://clinicaltrials.gov/study/NCT03043872 NCT03043872] | ||
+ | ##'''PRO analysis:''' Goldman JW, Garassino MC, Chen Y, Özgüroğlu M, Dvorkin M, Trukhin D, Statsenko G, Hotta K, Ji JH, Hochmair MJ, Voitko O, Havel L, Poltoratskiy A, Losonczy G, Reinmuth N, Patel N, Laud PJ, Shire N, Jiang H, Paz-Ares L. Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study. Lung Cancer. 2020 Nov;149:46-52. Epub 2020 Sep 10. [https://doi.org/10.1016/j.lungcan.2020.09.003 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32961445/ PubMed] | ||
+ | ##'''Update:''' Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Każarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. Epub 2020 Dec 4. [https://doi.org/10.1016/s1470-2045(20)30539-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33285097/ PubMed] | ||
+ | # '''KEYNOTE-604:''' Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gümüş M, Kato T, Kalemkerian GP, Luo Y, Ebiana V, Pietanza MC, Kim HR; KEYNOTE-604 Investigators. Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. J Clin Oncol. 2020 Jul 20;38(21):2369-2379. Epub 2020 May 29. [https://doi.org/10.1200/jco.20.00793 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32468956/ PubMed] [https://clinicaltrials.gov/study/NCT03066778 NCT03066778] | ||
+ | # '''CAPSTONE-1:''' Wang J, Zhou C, Yao W, Wang Q, Min X, Chen G, Xu X, Li X, Xu F, Fang Y, Yang R, Yu G, Gong Y, Zhao J, Fan Y, Liu Q, Cao L, Yao Y, Liu Y, Li X, Wu J, He Z, Lu K, Jiang L, Hu C, Zhao W, Zhang B, Shi W, Zhang X, Cheng Y; CAPSTONE-1 Study Group. Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022 Jun;23(6):739-747. Epub 2022 May 13. [https://doi.org/10.1016/s1470-2045(22)00224-8 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35576956/ PubMed] [https://clinicaltrials.gov/study/NCT03711305 NCT03711305] | ||
+ | #'''RATIONALE-312:''' Cheng Y, Fan Y, Zhao Y, Huang D, Li X, Zhang P, Kang M, Yang N, Zhong D, Wang Z, Yu Y, Zhang Y, Zhao J, Qin T, Chen C, Leaw S, Zheng W, Song Y; RATIONALE-312 Study Group. Tislelizumab Plus Platinum and Etoposide Versus Placebo Plus Platinum and Etoposide as First-Line Treatment for Extensive-Stage SCLC (RATIONALE-312): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 3 Clinical Trial. J Thorac Oncol. 2024 Jul;19(7):1073-1085. Epub 2024 Mar 7. [https://doi.org/10.1016/j.jtho.2024.03.008 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/38460751/ PubMed] [https://clinicaltrials.gov/study/NCT04005716 NCT04005716] | ||
− | ==Carboplatin, | + | ==Carboplatin & Etoposide (CE) & Atezolizumab {{#subobject:760b97|Regimen=1}}== |
− | {| class="wikitable" style=" | + | CE & Atezolizumab: '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide, Atezolizumab |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:6a356b|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/NEJMoa1809064 Horn et al. 2018 (IMpower133)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-194-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2016-06-06 to 2017-05-31 | ||
+ | |style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
+ | |[[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]] | ||
+ | | style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: 12.3 vs 10.3 mo<br>(HR 0.76, 95% CI 0.60-0.95) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10824371/ Rudin et al. 2023 (SKYSCRAPER-02)] | ||
+ | |2020-02 to 2021-03 | ||
+ | |style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Carboplatin_.26_Etoposide_.28CE.29.2C_Atezolizumab.2C_Tiragolumab_999|CE, Atezolizumab, Tiragolumab]] | ||
+ | | style="background-color:#ffffbf" |Did not meet co-primary endpoints of PFS/OS | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy for IMpower133 is based on the 2020 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] as follows: | ||
+ | **Cycles 1 to 4: AUC 5 IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] as follows: | ||
+ | **Cycles 1 to 4: 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | ====Immunotherapy==== | ||
+ | *[[Atezolizumab (Tecentriq)]] 1200 mg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''IMpower133:''' Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. Epub 2018 Sep 25. [https://doi.org/10.1056/NEJMoa1809064 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/30280641/ PubMed] [https://clinicaltrials.gov/study/NCT02763579 NCT02763579] | ||
+ | ##'''PRO analysis:''' Mansfield AS, Każarnowicz A, Karaseva N, Sánchez A, De Boer R, Andric Z, Reck M, Atagi S, Lee JS, Garassino M, Liu SV, Horn L, Wen X, Quach C, Yu W, Kabbinavar F, Lam S, Morris S, Califano R. Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. Ann Oncol. 2020 Feb;31(2):310-317. Epub 2019 Dec 9. [https://doi.org/10.1016/j.annonc.2019.10.021 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31959349/ PubMed] | ||
+ | ## '''Update:''' Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, Garassino MC, De Castro Carpeno J, Califano R, Nishio M, Orlandi F, Alatorre-Alexander J, Leal T, Cheng Y, Lee JS, Lam S, McCleland M, Deng Y, Phan S, Horn L. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021 Feb 20;39(6):619-630. Epub 2021 Jan 13. [https://doi.org/10.1200/jco.20.01055 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078320/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33439693/ PubMed] | ||
+ | #'''SKYSCRAPER-02:''' Rudin CM, Liu SV, Soo RA, Lu S, Hong MH, Lee JS, Bryl M, Dumoulin DW, Rittmeyer A, Chiu CH, Ozyilkan O, Johnson M, Navarro A, Novello S, Ozawa Y, Tam SH, Patil NS, Wen X, Huang M, Hoang T, Meng R, Reck M. SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer. J Clin Oncol. 2024 Jan 20;42(3):324-335. Epub 2023 Nov 17. [https://doi.org/10.1200/jco.23.01363 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10824371/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37976444/ PubMed] [https://clinicaltrials.gov/study/NCT04256421 NCT04256421] | ||
+ | #'''IMforte:''' [https://clinicaltrials.gov/study/NCT05091567 NCT05091567] | ||
+ | |||
+ | ==Carboplatin & Etoposide (CE) & Bevacizumab {{#subobject:d61f26|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:3eed0d|Variant=1}}=== | ===Regimen {{#subobject:3eed0d|Variant=1}}=== | ||
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/JCO.2010.29.3423 Spigel et al. 2011 (SALUTE)] |
− | |style="background-color:# | + | |2007-2008 |
− | |[[#Carboplatin_.26_Etoposide_.28EP. | + | | style="background-color:#1a9851" |Randomized Phase 2 (E-esc) |
− | |style="background-color:# | + | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]] |
+ | | style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint)<br>Median PFS: 5.5 vs 4.4 mo<br>(HR 0.53, 95% CI 0.32-0.86) | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1 | *[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1 | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | ====Targeted therapy==== | ||
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | ||
− | |||
'''21-day cycle for 4 cycles''' | '''21-day cycle for 4 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[#Bevacizumab_monotherapy|Bevacizumab]] maintenance | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''SALUTE:''' Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. [https://doi.org/10.1200/JCO.2010.29.3423 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21502556/ PubMed] [https://clinicaltrials.gov/study/NCT00403403 NCT00403403] | ||
+ | ==Carboplatin & Etoposide (CE) & Durvalumab {{#subobject:ddgb26|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:3cbz3d|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S0140-6736(19)32222-6 Paz-Ares et al. 2019 (CASPIAN)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-212-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2017-03-27 to 2018-05-29 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
+ | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]] | ||
+ | | style="background-color:#1a9850" |Superior OS<sup>1</sup> (primary endpoint)<br>Median OS: 12.9 vs 10.5 mo<br>(HR 0.75, 95% CI 0.62-0.91) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2021 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] as follows: | ||
+ | **Cycles 1 to 4: AUC 5 to 6 IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] as follows: | ||
+ | **Cycles 1 to 4: 80 to 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | ====Immunotherapy==== | ||
+ | *[[Durvalumab (Imfinzi)]] as follows: | ||
+ | **Cycles 1 to 4: 1500 mg IV once on day 1 | ||
+ | **Cycle 5 onwards: 1500 mg IV once on day 1 | ||
+ | '''21-day cycle for 4 cycles, then 28-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''CASPIAN:''' Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. Epub 2019 Oct 4. [https://doi.org/10.1016/S0140-6736(19)32222-6 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31590988/ PubMed] [https://clinicaltrials.gov/study/NCT03043872 NCT03043872] | ||
+ | ##'''PRO analysis:''' Goldman JW, Garassino MC, Chen Y, Özgüroğlu M, Dvorkin M, Trukhin D, Statsenko G, Hotta K, Ji JH, Hochmair MJ, Voitko O, Havel L, Poltoratskiy A, Losonczy G, Reinmuth N, Patel N, Laud PJ, Shire N, Jiang H, Paz-Ares L. Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study. Lung Cancer. 2020 Nov;149:46-52. Epub 2020 Sep 10. [https://doi.org/10.1016/j.lungcan.2020.09.003 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32961445/ PubMed] | ||
+ | ##'''Update:''' Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Każarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. Epub 2020 Dec 4. [https://doi.org/10.1016/s1470-2045(20)30539-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33285097/ PubMed] | ||
− | + | ==Carboplatin & Etoposide (CE) & Serplulimab {{#subobject:ijg126|Regimen=1}}== | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:kcla3d|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9516323/ Cheng et al. 2022 (ASTRUM-005)] | ||
+ | |2019-09-12 to 2021-04-27 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
+ | |[[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]] | ||
+ | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 15.4 vs 10.9 mo<br>(HR 0.63, 95% CI 0.49-0.82) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: the original capped dose of carboplatin was 800 mg; this was modified in a protocol amendment.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] as follows: | ||
+ | **Cycles 1 to 4: AUC 5 (maximum dose of 750 mg) IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] as follows: | ||
+ | **Cycles 1 to 4: 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | ====Immunotherapy==== | ||
+ | *[[Serplulimab (Hansizhuang)]] 4.5 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''ASTRUM-005:''' Cheng Y, Han L, Wu L, Chen J, Sun H, Wen G, Ji Y, Dvorkin M, Shi J, Pan Z, Shi J, Wang X, Bai Y, Melkadze T, Pan Y, Min X, Viguro M, Li X, Zhao Y, Yang J, Makharadze T, Arkania E, Kang W, Wang Q, Zhu J; ASTRUM-005 Study Group. Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer: The ASTRUM-005 Randomized Clinical Trial. JAMA. 2022 Sep 27;328(12):1223-1232. [https://doi.org/10.1001/jama.2022.16464 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9516323/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36166026/ PubMed] [https://clinicaltrials.gov/study/NCT04063163 NCT04063163] | ||
+ | ==Carboplatin & Etoposide (CE) & Tislelizumab {{#subobject:ijtix26|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:kclzid|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/j.jtho.2024.03.008 Cheng et al. 2024 (RATIONALE-312)] | ||
+ | |2019-07-22 to 2021-04-21 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]] | ||
+ | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 15.5 vs 13.5 mo<br>(HR 0.75, 95% CI 0.61-0.93) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] as follows: | ||
+ | **Cycles 1 to 4: AUC 5 IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] as follows: | ||
+ | **Cycles 1 to 4: 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | ====Immunotherapy==== | ||
+ | *[[Tislelizumab (Baizean)]] 200 mg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | #'''RATIONALE-312:''' Cheng Y, Fan Y, Zhao Y, Huang D, Li X, Zhang P, Kang M, Yang N, Zhong D, Wang Z, Yu Y, Zhang Y, Zhao J, Qin T, Chen C, Leaw S, Zheng W, Song Y; RATIONALE-312 Study Group. Tislelizumab Plus Platinum and Etoposide Versus Placebo Plus Platinum and Etoposide as First-Line Treatment for Extensive-Stage SCLC (RATIONALE-312): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 3 Clinical Trial. J Thorac Oncol. 2024 Jul;19(7):1073-1085. Epub 2024 Mar 7. [https://doi.org/10.1016/j.jtho.2024.03.008 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/38460751/ PubMed] [https://clinicaltrials.gov/study/NCT04005716 NCT04005716] |
− | ==Carboplatin & Irinotecan ( | + | ==Carboplatin & Irinotecan {{#subobject:b2ac71|Regimen=1}}== |
− | {| class="wikitable" style=" | + | IC: '''<u>I</u>'''rinotecan & '''<u>C</u>'''arboplatin |
+ | <br>IP: '''<u>I</u>'''rinotecan & '''<u>P</u>'''araplatin (Carboplatin) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, AUC 4/175 {{#subobject:3de550|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2007.15.7545 Hermes et al. 2008] | ||
+ | |2001-2005 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
+ | |[[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]] | ||
+ | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 8.5 vs 7.1 mo<br>(HR 0.71, 95% CI 0.53-0.94) | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | + | ====Chemotherapy==== | |
− | ===Regimen {{#subobject:38a7ba|Variant=1}}=== | + | *[[Carboplatin (Paraplatin)]] AUC 4 (Chatelut formula) IV once on day 1 |
− | {| | + | *[[Irinotecan (Camptosar)]] 175 mg/m<sup>2</sup> IV once on day 1 |
− | | | + | '''21-day cycle for 4 cycles''' |
− | |[[Levels_of_Evidence#Evidence| | + | </div></div><br> |
− | | | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |[[Levels_of_Evidence# | + | ===Regimen variant #2, AUC 5/150 {{#subobject:38a7ba|Variant=1}}=== |
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1093/annonc/mdj137 Schmittel et al. 2006] |
− | |style="background-color:# | + | |2002-2008 |
− | |[[ | + | | style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic) |
− | |style="background-color:# | + | |[[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]] |
+ | | style="background-color:#d9ef8b" |Might have superior OS (secondary endpoint) | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Carboplatin (Paraplatin)]] AUC 5 | + | *[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 1 |
− | *[[Irinotecan (Camptosar)]] 50 mg/m<sup>2</sup> | + | *[[Irinotecan (Camptosar)]] 50 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15 |
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]] IV once per day on days 1, 8, 15, prior to chemotherapy |
− | *[[ | ||
*[[Loperamide (Imodium)]] 4 mg PO prn first episode of diarrhea, then 2 mg PO Q2H until diarrhea stops | *[[Loperamide (Imodium)]] 4 mg PO prn first episode of diarrhea, then 2 mg PO Q2H until diarrhea stops | ||
− | |||
'''28-day cycle for up to 6 cycles''' | '''28-day cycle for up to 6 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Schmittel A, Fischer von Weikersthal L, Sebastian M, Martus P, Schulze K, Hortig P, Reeb M, Thiel E, Keilholz U. A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer. Ann Oncol. 2006 Apr;17(4):663-7. Epub 2006 Jan 19. [ | + | # Schmittel A, Fischer von Weikersthal L, Sebastian M, Martus P, Schulze K, Hortig P, Reeb M, Thiel E, Keilholz U. A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer. Ann Oncol. 2006 Apr;17(4):663-7. Epub 2006 Jan 19. [https://doi.org/10.1093/annonc/mdj137 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16423848/ PubMed] |
− | ## '''Update:''' Schmittel A, Sebastian M, Fischer von Weikersthal L, Martus P, Gauler TC, Kaufmann C, Hortig P, Fischer JR, Link H, Binder D, Fischer B, Caca K, Eberhardt WE, Keilholz U; Arbeitsgemeinschaft Internistische Onkologie Thoracic Oncology Study Group. A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol. 2011 Aug;22(8):1798-804. Epub 2011 Jan 25. [ | + | ## '''Update:''' Schmittel A, Sebastian M, Fischer von Weikersthal L, Martus P, Gauler TC, Kaufmann C, Hortig P, Fischer JR, Link H, Binder D, Fischer B, Caca K, Eberhardt WE, Keilholz U; Arbeitsgemeinschaft Internistische Onkologie Thoracic Oncology Study Group. A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol. 2011 Aug;22(8):1798-804. Epub 2011 Jan 25. [https://doi.org/10.1093/annonc/mdq652 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21266516/ PubMed] |
− | + | # Hermes A, Bergman B, Bremnes R, Ek L, Fluge S, Sederholm C, Sundstrøm S, Thaning L, Vilsvik J, Aasebø U, Sörenson S. Irinotecan plus carboplatin versus oral etoposide plus carboplatin in extensive small-cell lung cancer: a randomized phase III trial. J Clin Oncol. 2008 Sep 10;26(26):4261-7. [https://doi.org/10.1200/JCO.2007.15.7545 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18779613/ PubMed] | |
− | == | + | ==Carboplatin & Paclitaxel (CP) & Ipilimumab {{#subobject:9695b3|Regimen=1}}== |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, phased ipilimumab {{#subobject:7dbd39|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | | rowspan="2" |[https://doi.org/10.1093/annonc/mds213 Reck et al. 2012 (CA184-041<sub>SCLC</sub>)] | ||
+ | |rowspan=2|2008-2009 | ||
+ | | rowspan="2" style="background-color:#1a9851" |Randomized Phase 2 (E-esc) | ||
+ | |1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_888|CP]] | ||
+ | | style="background-color:#91cf60" |Seems to have superior irPFS (primary endpoint) | ||
+ | |- | ||
+ | |2. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Ipilimumab|CP & Ipilimumab]]; concurrent Ipilimumab | ||
+ | | style="background-color:#d3d3d3" |Not reported | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | + | ====Chemotherapy==== | |
− | ===Regimen {{#subobject: | + | *[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1 |
− | {| | + | *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1 |
− | | | + | ====Immunotherapy==== |
− | |[[Levels_of_Evidence#Evidence| | + | *[[Ipilimumab (Yervoy)]] as follows: |
− | | | + | **Cycles 3 to 6: 10 mg/kg IV once on day 1 |
− | |[[Levels_of_Evidence# | + | '''21-day cycle for up to 6 cycles''' |
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[#Ipilimumab_monotherapy|Ipilimumab]] maintenance | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, concurrent ipilimumab {{#subobject:069d62|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |rowspan=2|[ | + | | rowspan="2" |[https://doi.org/10.1093/annonc/mds213 Reck et al. 2012 (CA184-041<sub>SCLC</sub>)] |
− | |rowspan=2 style="background-color:# | + | |rowspan=2|2008-2009 |
− | |[[ | + | | rowspan="2" style="background-color:#1a9851" |Randomized Phase 2 (E-esc) |
− | |style="background-color:# | + | |1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_888|CP]] |
− | + | | style="background-color:#ffffbf" |Did not meet secondary endpoints | |
|- | |- | ||
− | |[[ | + | |2. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Ipilimumab|CP & Ipilimumab]]; phased Ipilimumab |
− | |style="background-color:# | + | | style="background-color:#d3d3d3" |Not reported |
− | |||
|- | |- | ||
|} | |} | ||
+ | ''Note: all efficacy endpoints in the ED-SCLC cohort were secondary.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1 |
− | *[[ | + | *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1 |
− | *[[ | + | ====Immunotherapy==== |
− | + | *[[Ipilimumab (Yervoy)]] as follows: | |
− | '''21-day cycle for | + | **Cycles 1 to 4: 10 mg/kg IV once on day 1 |
− | + | '''21-day cycle for up to 6 cycles''' | |
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | ==== | + | ====Subsequent treatment==== |
− | + | *[[#Ipilimumab_monotherapy|Ipilimumab]] maintenance | |
− | * | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | # | + | # '''CA184-041<sub>SCLC</sub>:''' Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Lu H, Cuillerot JM, Lynch TJ. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol. 2013 Jan;24(1):75-83. Epub 2012 Aug 2. [https://doi.org/10.1093/annonc/mds213 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22858559/ PubMed] [https://clinicaltrials.gov/study/NCT00527735 NCT00527735] |
− | + | ==Cisplatin & Etoposide (EP) {{#subobject:ec90cd|Regimen=1}}== | |
− | == | + | EP: '''<u>E</u>'''toposide and '''<u>P</u>'''latinol (Cisplatin) |
− | {| class="wikitable" style=" | + | <br>PE: '''<u>P</u>'''latinol (Cisplatin) and '''<u>E</u>'''toposide |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, 60/300 {{#subobject:dd1718|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002146/ Oh et al. 2016 (COMBAT)] | ||
+ | |2009-2013 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Belotecan_.26_Cisplatin|BP]] | ||
+ | | style="background-color:#eeee01" |Non-inferior RR | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: the total number of planned cycles is not described in the manuscript; total duration information here was provided by the authors.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | '''21-day cycle for 4 to 8 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 60/360 {{#subobject:5c4b41|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2005.04.8595 Hanna et al. 2006] | ||
+ | |2000-2003 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cisplatin_.26_Irinotecan_.28IC.29_2|Cisplatin & Irinotecan]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ Seckl et al. 2017 (LUNGSTAR)] | ||
+ | |2007-2012 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_999|CE & Pravastatin]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_999|EP & Pravastatin]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>OS24: 14.1% vs 13.2%<br>(HR 0.99, 95% CI 0.86-1.14) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | ====Supportive therapy==== | ||
+ | *Per Hanna et al. 2006: | ||
+ | **[[:Category:Granulocyte colony-stimulating factors|G-CSF]] used according to 1999 American Society of Clinical Oncology guidelines | ||
+ | **"Erythropoietin was allowed at the discretion of the treating physician." | ||
+ | '''21-day cycle for 4 to 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #3, 60/440, 1 day of oral etoposide per cycle {{#subobject:47c27e|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ Seckl et al. 2017 (LUNGSTAR)] | ||
+ | |2007-2012 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_999|CE & Pravastatin]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_999|EP & Pravastatin]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>OS24: 14.1% vs 13.2%<br>(HR 0.99, 95% CI 0.86-1.14) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2, then 100 mg PO twice per day on day 3 | ||
+ | '''21-day cycle for up to 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #4, 60/520, 2 days of oral etoposide per cycle {{#subobject:ae04e8|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ Seckl et al. 2017 (LUNGSTAR)] | ||
+ | |2007-2012 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_999|CE & Pravastatin]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_999|EP & Pravastatin]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>OS24: 14.1% vs 13.2%<br>(HR 0.99, 95% CI 0.86-1.14) | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | + | ====Chemotherapy==== | |
− | ===Regimen {{#subobject: | + | *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1 |
− | {| | + | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once on day 1, then 100 mg PO twice per day on days 2 & 3 |
− | | | + | '''21-day cycle for up to 6 cycles''' |
− | |[[Levels_of_Evidence#Evidence| | + | </div></div><br> |
− | | | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |[[Levels_of_Evidence#Efficacy| | + | ===Regimen variant #5, 70/300 {{#subobject:5b9a41|Variant=1}}=== |
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1089/107999099314180 Ruotsalainen et al. 1999] | ||
+ | |Not reported in abstract | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cisplatin_.26_Etoposide_.28EP.29_.26_Interferon_alfa_999|EP & IFN-alpha]] | ||
+ | | style="background-color:#ffffbf" |Did not meet endpoint of OS50% | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334001/ Kim et al. 2018 (CRCST-L-0001)] |
− | |style="background-color:# | + | |2006-2011 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#Cisplatin_.26_Irinotecan_.28IC.29_2|Cisplatin & Irinotecan]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | '' | + | ====Chemotherapy==== |
− | + | *[[Cisplatin (Platinol)]] 70 mg/m<sup>2</sup> IV once on day 1 | |
− | === | + | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 |
− | # | + | '''21-day cycle for up to 6 cycles''' |
− | + | </div></div><br> | |
− | = | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | + | ===Regimen variant #6, 75/240, split cisplatin {{#subobject:8907be|Variant=1}}=== | |
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360311/ Okamoto et al. 2007 (JCOG 9702)] | ||
+ | |1998-2004 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ===Regimen # | + | ====Chemotherapy==== |
− | {| | + | *[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 3 |
− | | | + | *[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV once per day on days 1 to 3 |
− | |[[Levels_of_Evidence#Evidence| | + | '''21- to 28-day cycle for 4 cycles''' |
− | | | + | </div></div><br> |
− | |[[Levels_of_Evidence#Efficacy| | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #7, 75/300 {{#subobject:da2da4|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |rowspan=2|[https://doi.org/10.1097/jto.0b013e318260de75 Fink et al. 2012 (GSK 104864-A/479)] | ||
+ | |rowspan=2|2002-2006 | ||
+ | |rowspan=2 style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1. [[#Cisplatin_.26_Topotecan_888|Cisplatin & Topotecan]] | ||
+ | | style="background-color:#eeee01" |Non-inferior OS | ||
+ | |- | ||
+ | |2. [[#Etoposide_.26_Topotecan_999|Etoposide & Topotecan]] | ||
+ | | style="background-color:#d3d3d3" |Not reported | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2010.29.3423 Spigel et al. 2011 (SALUTE)] | ||
+ | |2007-2008 | ||
+ | | style="background-color:#1a9851" |Randomized Phase 2 (C) | ||
+ | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Bevacizumab|CE & Bevacizumab]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Bevacizumab|EP & Bevacizumab]] | ||
+ | | style="background-color:#fc8d59" |Seems to have inferior PFS | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2016.67.6601 Reck et al. 2016 (CA184-156)] | ||
+ | |2012-2014 | ||
+ | |style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[Stub#Carboplatin_.26_Etoposide_.28CE.29_.26_Ipilimumab|CE & Ipilimumab]]<br>1b. [[Stub#EP_.26_Ipilimumab|EP & Ipilimumab]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 10.9 vs 11 mo<br>(HR 1.06, 95% CI 0.92-1.23) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ Rudin et al. 2020 (KEYNOTE-604)] | ||
+ | |2017-05-15 to 2018-07-30 | ||
+ | |style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[Small_cell_lung_cancer_-_historical#Carboplatin_.26_Etoposide_.28CE.29_.26_Pembrolizumab|CE & Pembrolizumab]]<br>1b. [[Small_cell_lung_cancer_-_historical#Cisplatin_.26_Etoposide_.28EP.29_.26_Pembrolizumab|EP & Pembrolizumab]] | ||
+ | | style="background-color:#fc8d59" |Seems to have inferior OS | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.jtho.2024.03.008 Cheng et al. 2024 (RATIONALE-312)] |
− | |style="background-color:# | + | |2019-07-22 to 2021-04-21 |
− | |[[# | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Tislelizumab|CE & Tislelizumab]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Tislelizumab|EP & Tislelizumab]] |
+ | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | + | '''21-day cycle for varying durations: 4 cycles (KEYNOTE-604, RATIONALE-312, SALUTE); 6 cycles (CA184-156, GSK 104864-A/479)''' | |
− | '''21-day cycle for 4 cycles''' | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ===Regimen # | + | ===Regimen variant #8, 75/300, split cisplatin {{#subobject:a51a22|Variant=1}}=== |
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | |''' | + | !style="width: 20%"|Study |
− | + | !style="width: 20%"|Dates of enrollment | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.1985.3.11.1471 Evans et al. 1985] | ||
+ | |1981-1984 | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2016.69.4844 Tiseo et al. 2017 (GOIRC-AIFA FARM6PMFJM)] | ||
+ | |2009-2015 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cisplatin_.26_Etoposide_.28EP.29_.26_Bevacizumab_999|EP & Bevacizumab]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 9.8 vs 8.9 mo<br>(HR 1.28, 95% CI 0.94-1.72) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: in Evans et al. 1985, patients with disease responding to therapy received prophylactic cranial irradiation, 400 cGy fractions given daily x 5 fractions (total dose: 2000 cGy) over 5 days between cycles 3 and 4; Locoregional radiation therapy was only used if symptoms persisted after 6 cycles of treatment: Radiation therapy, 250 cGy/rad fractions x 10 fractions (total dose: 2500 cGy/rad), given after cycle 6 of chemotherapy.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV slow push once per day on days 1 to 3, '''given second''' | ||
+ | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over at least 30 minutes once per day on days 1 to 3, '''given first''' | ||
+ | ====Supportive therapy==== | ||
+ | *[[Dexamethasone (Decadron)]] 10 mg IV once per day on days 1 to 3, prior to chemotherapy | ||
+ | *[[Metoclopramide (Reglan)]] 10 mg IV or PO once per day on days 1 to 3, prior to chemotherapy | ||
+ | *[[Prochlorperazine (Compazine)]] 10 mg IM or PO once per day on days 1 to 3, prior to chemotherapy | ||
+ | *"No special efforts were made to hydrate the patients," though PO fluid intake was encouraged, and 500 mL normal saline was given with etoposide infusion. | ||
+ | '''21- to 28-day cycle for up to 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #9, 75/390, split cisplatin {{#subobject:3ed519|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/JCO.1995.13.8.1871 Miller et al. 1995] |
− | |style="background-color:# | + | |1990-1993 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]; oral etoposide |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cisplatin (Platinol)]] | + | *[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 3 |
− | *[[Etoposide (Vepesid)]] | + | *[[Etoposide (Vepesid)]] 130 mg/m<sup>2</sup> IV once per day on days 1 to 3 |
− | + | '''21-day cycle for 8 cycles''' | |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #10, 75/700, 3 days of oral etoposide per cycle {{#subobject:807314|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | '''21-day cycle for | + | !style="width: 20%"|Study |
− | + | !style="width: 20%"|Dates of enrollment | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | + | !style="width: 20%"|Comparator | |
− | ===Regimen #3 {{#subobject:807314|Variant=1}}=== | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | {| | ||
− | | | ||
− | |[[Levels_of_Evidence#Evidence| | ||
− | | | ||
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2002.12.111 Sundstrøm et al. 2002] |
− | |style="background-color:# | + | |1989-1994 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
− | |style="background-color:# | + | |[[Small_cell_lung_cancer_-_historical#CEV_.28Cyclophosphamide.2FEpirubicin.29|CEV]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
|} | |} | ||
− | ''Note: Patients in Sundstrøm et al. 2002 with extensive stage disease did not routinely receive radiation therapy. "However, chest or cranial irradiation was optional if severe symptoms could not be palliated by chemotherapy."'' | + | ''Note: Patients in Sundstrøm et al. 2002 with extensive stage disease did not routinely receive radiation therapy. "However, chest or cranial irradiation was optional if severe symptoms could not be palliated by chemotherapy." Oral etoposide to be taken on an empty stomach.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
− | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> PO once per day on days 2 to 4 | + | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> PO once per day on days 2 to 4 |
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*"Standard prehydration and posthydration procedures were followed in conjunction with cisplatin administration." | *"Standard prehydration and posthydration procedures were followed in conjunction with cisplatin administration." | ||
− | |||
'''21-day cycle for up to 5 cycles''' | '''21-day cycle for up to 5 cycles''' | ||
− | + | </div></div><br> | |
− | ===Regimen # | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| | + | ===Regimen variant #11, 80/240 {{#subobject:7b3c2e|Variant=1}}=== |
− | | | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | |[[Levels_of_Evidence#Evidence|'' | + | !style="width: 20%"|Study |
− | |''' | + | !style="width: 20%"|Dates of enrollment |
− | |[[Levels_of_Evidence#Efficacy| | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.1994.12.10.2022 Ihde et al. 1994] | ||
+ | |1983-1991 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]; high-dose | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2005.09.071 Niell et al. 2005 (CALGB 9732)] | ||
+ | |1998-2001 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cisplatin_.26_Etoposide_.28EP.29_.26_Paclitaxel_999|PET]] | ||
+ | | style="background-color:#ffffbf" |Did not meet endpoints of FFS50%/OS50% | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: Concurrent radiation therapy with the start of chemotherapy was given to patients with brain metastases, epidural metastases, and impending pathologic bone fractures.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | ====Supportive therapy==== | ||
+ | *"Half-normal saline was infused for 2 to 6 hours with cisplatin, usually in conjunction with a diuretic." | ||
+ | *[[:Category:Steroids|Corticosteroids]] were usually given for patients receiving radiation therapy for brain and epidural metastases. | ||
+ | '''21-day cycle for 4 to 8 cycles''' | ||
+ | ====CNS therapy==== | ||
+ | *Patients with carcinomatous meningitis received [[Methotrexate (MTX)]] IT (dose/schedule not specified) and radiation to functionally compromised areas of the CNS | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *Ihde et al. 1994, CR after 4 cycles: [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]] continuation x 4 cycles. Some patients were randomized to receive prophylactic cranial irradiation. Radiation could also be given at the patient's request. No details about dose/schedule given. | ||
+ | *Ihde et al. 1994, PR, no response, or progressive disease: Salvage [[Small_cell_lung_cancer_-_historical#CAV_3|CAV]] or "an individualized 3-drug in vitro-selected regimen (IVSR) during cycles 5 to 8 if drug-sensitivity testing data were available." | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #12, 80/300 {{#subobject:26b7f1|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | | rowspan="2" |[https://doi.org/10.1093/jnci/83.12.855 Fukuoka et al. 1991 (JCOG8502)] | ||
+ | |rowspan=2|1985-1988 | ||
+ | | rowspan="2" style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1. [[Small_cell_lung_cancer_-_historical#CAV_2|CAV]] | ||
+ | | style="background-color:#d3d3d3" |Not reported | ||
+ | |- | ||
+ | |2. [[Small_cell_lung_cancer_-_historical#CAV.2FPE|CAV/PE]] | ||
+ | | style="background-color:#fee08b" |Might have inferior OS | ||
+ | |- | ||
+ | |[https://doi.org/10.1159/000227087 Miyamoto et al. 1992] | ||
+ | |Not reported in abstract | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[Stub#PEI|PEI]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/NEJMoa003034 Noda et al. 2002 (JCOG 9511)] | ||
+ | |1995-1998 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cisplatin_.26_Irinotecan_.28IC.29_2|IP]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2005.03.3332 Eckardt et al. 2006 (GSK 104864-A/389)] | ||
+ | |2001-2003 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cisplatin_.26_Topotecan_888|Cisplatin & Topotecan]] | ||
+ | | style="background-color:#eeee01" |Non-inferior OS | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684855/ Lara et al. 2009 (SWOG S0124)] | ||
+ | |2002-2007 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cisplatin_.26_Irinotecan_.28IC.29_2|IP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
+ | |- | ||
+ | |[https://ar.iiarjournals.org/content/30/7/3031.long Baka et al. 2010] | ||
+ | |2002-2006 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cisplatin_.26_Etoposide_.28EP.29.2FTopotecan_monotherapy_999|EP/T]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
+ | |- | ||
+ | |[https://doi.org/10.1093/annonc/mdq036 Zatloukal et al. 2010] | ||
+ | |2003-2007 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cisplatin_.26_Irinotecan_.28IC.29_2|IP]] | ||
+ | | style="background-color:#eeee01" |Non-inferior OS | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429175/ Ready et al. 2015 (CALGB 30504)] | ||
+ | |2007-2011 | ||
+ | | style="background-color:#91cf61" |Non-randomized part of phase 2 RCT | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826513/ Sun et al. 2016 (D0750018)] |
− | |style="background-color:# | + | |2008-2010 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#Amrubicin_.26_Cisplatin_333|Amrubicin & Cisplatin]] |
+ | | style="background-color:#fee08b" |Might have inferior OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | + | **Alternative scheduling: JCOG8502 & Miyamoto et al. 1992 gave etoposide on days 1, 3, 5 | |
− | ====Supportive | + | ====Supportive therapy==== |
*"Hydration and administration of antiemetic drugs." | *"Hydration and administration of antiemetic drugs." | ||
− | + | '''21-day cycle for 4 to 6 cycles''' | |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *Baka et al. 2010: [[#Topotecan_monotherapy_888|Topotecan]] consolidation x 4 | ||
+ | *CALGB 30504, SD or better: [[Small_cell_lung_cancer_-_null_regimens#Observation_2|Observation]] versus [[#Sunitinib_monotherapy|sunitinib]] maintenance | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #13, 80/360 {{#subobject:1cbnd3|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2004.00.9969 Thatcher et al. 2005 (MRC LU21)] | ||
+ | |1996-03 to 2002-02 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#ICE-V|ICE-V]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 2 & 3, then 240 mg/m<sup>2</sup> PO once on day 3 | ||
+ | '''21-day cycle for 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #14, 80/400, split cisplatin {{#subobject:d389d3|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.1995.13.10.2594 Loehrer et al. 1995] | ||
+ | |1989-1993 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[Small_cell_lung_cancer_-_historical#VIP|VIP]] | ||
+ | | style="background-color:#fc8d59" |Seems to have inferior OS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 4 | ||
+ | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 4 | ||
'''21-day cycle for 4 cycles''' | '''21-day cycle for 4 cycles''' | ||
− | + | </div></div><br> | |
− | ===Regimen # | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| | + | ===Regimen variant #15, 80/600, 2 days of oral etoposide per cycle {{#subobject:998892|Variant=1}}=== |
− | |''' | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Study |
− | | | + | !style="width: 20%"|Dates of enrollment |
− | |[[Levels_of_Evidence#Efficacy| | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527803/ Baka et al. 2008] | ||
+ | |1999-2005 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
+ | |[[Small_cell_lung_cancer_-_historical#CDE|ACE]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS12 | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once on day 1, then 240 mg/m<sup>2</sup>/day PO on days 2 & 3 | ||
+ | '''21-day cycle for 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #16, 100/300 {{#subobject:5b54c7|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.3816/clc.2004.n.031 Artal-Cortés et al. 2004] | ||
+ | |1994-1998 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cisplatin_.26_Epirubicin_999|Cisplatin & Epirubicin]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1093/jnci/93.4.300 Pujol et al. 2001 (FNCLCC 95012)] |
− | |style="background-color:# | + | |1996-1999 |
− | | | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[Small_cell_lung_cancer_-_historical#PCDE|PCDE]] |
+ | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cisplatin (Platinol)]] | + | *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 2 |
− | *[[Etoposide (Vepesid)]] | + | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 |
− | + | '''21-day cycle for 6 cycles''' | |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #17, 100/400, split cisplatin {{#subobject:f8e87a|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 20%"|Study | |
− | + | !style="width: 20%"|Dates of enrollment | |
− | '''21-day cycle for | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | + | !style="width: 20%"|Comparator | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
− | + | |- | |
− | + | |[https://doi.org/10.1200/JCO.1992.10.2.282 Roth et al. 1992] | |
− | + | |1985-1989 | |
− | + | | style="background-color:#1a9851" |Phase 3 (C) | |
− | ===Regimen # | + | |1. [[Small_cell_lung_cancer_-_historical#CAV_2|CAV]]<br>2. [[Small_cell_lung_cancer_-_historical#CAV.2FPE|CAV/PE]] |
− | {| | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS50% |
− | | | ||
− | |[[Levels_of_Evidence#Evidence| | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.1995.13.6.1436 Hainsworth et al. 1995] |
− | |style="background-color:# | + | |1992-1993 |
+ | | style="background-color:#1a9851" |Randomized Phase 2 (E-RT-switch-ic) | ||
+ | |[[#Cisplatin_.26_Etoposide_phosphate_888|Cisplatin & Etoposide phosphate]] | ||
+ | | style="background-color:#d3d3d3" |Not compared | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cisplatin (Platinol)]] | + | *[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5 |
− | *[[Etoposide (Vepesid)]] | + | *[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV once per day on days 1 to 5 |
− | + | '''21-day cycle for 4 cycles''' | |
− | + | </div></div> | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | '''21 | ||
− | |||
===References=== | ===References=== | ||
− | # Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. [ | + | # Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. [https://doi.org/10.1200/jco.1985.3.11.1471 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2997406/ PubMed] |
− | # Ihde DC, Mulshine JL, Kramer BS, Steinberg SM, Linnoila RI, Gazdar AF, Edison M, Phelps RM, Lesar M, Phares JC | + | # '''JCOG8502:''' Fukuoka M, Furuse K, Saijo N, Nishiwaki Y, Ikegami H, Tamura T, Shimoyama M, Suemasu K. Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer. J Natl Cancer Inst. 1991 Jun 19;83(12):855-61. [https://doi.org/10.1093/jnci/83.12.855 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/1648142/ PubMed] |
− | # Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, Fukuoka M, Mori K, Watanabe K, Tamura T, Yamamoto S, Saijo N; | + | # Miyamoto H, Nakabayashi T, Isobe H, Akita H, Kawakami Y, Arimoto T, Asakawa M, Suzuki A, Fujikane T, Shimizu T, Sakai E. A phase III comparison of etoposide/cisplatin with or without added ifosfamide in small-cell lung cancer. Oncology. 1992;49(6):431-5. [https://doi.org/10.1159/000227087 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/1334539/ PubMed] |
− | # Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. [ | + | # Roth BJ, Johnson DH, Einhorn LH, Schacter LP, Cherng NC, Cohen HJ, Crawford J, Randolph JA, Goodlow JL, Broun GO, Omura GA, Greco FA; Southeastern Cancer Study Group. Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol. 1992 Feb;10(2):282-91. [https://doi.org/10.1200/JCO.1992.10.2.282 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/1310103/ PubMed] |
− | # Niell HB, Herndon JE 2nd, Miller AA, Watson DM, Sandler AB, Kelly K, Marks RS, Perry MC, Ansari RH, Otterson G, Ellerton J, Vokes EE, Green MR; | + | # Ihde DC, Mulshine JL, Kramer BS, Steinberg SM, Linnoila RI, Gazdar AF, Edison M, Phelps RM, Lesar M, Phares JC, Grayson J, Minna JD, Johnson BE. Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. J Clin Oncol. 1994 Oct;12(10):2022-34. [https://doi.org/10.1200/jco.1994.12.10.2022 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/7931470/ PubMed] |
+ | # Hainsworth JD, Levitan N, Wampler GL, Belani CP, Seyedsadr MS, Randolph J, Schacter LP, Greco FA. Phase II randomized study of cisplatin plus etoposide phosphate or etoposide in the treatment of small-cell lung cancer. J Clin Oncol. 1995 Jun;13(6):1436-42. [https://doi.org/10.1200/jco.1995.13.6.1436 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7751890/ PubMed] | ||
+ | # Miller AA, Herndon JE 2nd, Hollis DR, Ellerton J, Langleben A, Richards F 2nd, Green MR; [[Study_Groups#CALGB|CALGB]]. Schedule dependency of 21-day oral versus 3-day intravenous etoposide in combination with intravenous cisplatin in extensive-stage small-cell lung cancer: a randomized phase III study of the Cancer and Leukemia Group B. J Clin Oncol. 1995 Aug;13(8):1871-9. [https://doi.org/10.1200/JCO.1995.13.8.1871 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/7636529/ PubMed] | ||
+ | # Loehrer PJ Sr, Ansari R, Gonin R, Monaco F, Fisher W, Sandler A, Einhorn LH; Hoosier Oncology Group. Cisplatin plus etoposide with and without ifosfamide in extensive small-cell lung cancer: a Hoosier Oncology Group study. J Clin Oncol. 1995 Oct;13(10):2594-9. [https://doi.org/10.1200/JCO.1995.13.10.2594 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/7595712/ PubMed] | ||
+ | # Ruotsalainen TM, Halme M, Tamminen K, Szopinski J, Niiranen A, Pyrhönen S, Riska H, Maasilta P, Jekunen A, Mäntylä M, Kajanti M, Joensuu H, Sarna S, Cantell K, Mattson K. Concomitant chemotherapy and IFN-alpha for small cell lung cancer: a randomized multicenter phase III study. J Interferon Cytokine Res. 1999 Mar;19(3):253-9. [https://doi.org/10.1089/107999099314180 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10213464/ PubMed] | ||
+ | # '''FNCLCC 95012:''' Pujol JL, Daurès JP, Rivière A, Quoix E, Westeel V, Quantin X, Breton JL, Lemarié E, Poudenx M, Milleron B, Moro D, Debieuvre D, Le Chevalier T. Etoposide plus cisplatin with or without the combination of 4'-epidoxorubicin plus cyclophosphamide in treatment of extensive small-cell lung cancer: a French Federation of Cancer Institutes multicenter phase III randomized study. J Natl Cancer Inst. 2001 Feb 21;93(4):300-8. [https://doi.org/10.1093/jnci/93.4.300 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11181777/ PubMed] [https://clinicaltrials.gov/study/NCT00003606 NCT00003606] | ||
+ | # '''JCOG 9511:''' Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, Fukuoka M, Mori K, Watanabe K, Tamura T, Yamamoto S, Saijo N; [[Study_Groups#JCOG|JCOG]]. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):85-91. [https://doi.org/10.1056/NEJMoa003034 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11784874/ PubMed] | ||
+ | # Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. [https://doi.org/10.1200/jco.2002.12.111 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12488411/ PubMed] | ||
+ | # Artal-Cortés A, Gomez-Codina J, Gonzalez-Larriba JL, Barneto I, Carrato A, Isla D, Camps C, Garcia-Giron C, Font A, Meana A, Lomas M, Vadell C, Arrivi A, Alonso C, Maestu I, Campbell J, Rosell R. Prospective randomized phase III trial of etoposide/cisplatin versus high-dose epirubicin/cisplatin in small-cell lung cancer. Clin Lung Cancer. 2004 Nov;6(3):175-83. [https://doi.org/10.3816/clc.2004.n.031 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15555219/ PubMed] | ||
+ | # '''CALGB 9732:''' Niell HB, Herndon JE 2nd, Miller AA, Watson DM, Sandler AB, Kelly K, Marks RS, Perry MC, Ansari RH, Otterson G, Ellerton J, Vokes EE, Green MR; [[Study_Groups#CALGB|CALGB]]. Randomized phase III intergroup trial of etoposide and cisplatin with or without paclitaxel and granulocyte colony-stimulating factor in patients with extensive-stage small-cell lung cancer: Cancer and Leukemia Group B Trial 9732. J Clin Oncol. 2005 Jun 1;23(16):3752-9. [https://doi.org/10.1200/JCO.2005.09.071 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15923572/ PubMed] [https://clinicaltrials.gov/study/NCT00003299 NCT00003299] | ||
+ | #'''MRC LU21:''' Thatcher N, Qian W, Clark PI, Hopwood P, Sambrook RJ, Owens R, Stephens RJ, Girling DJ. Ifosfamide, carboplatin, and etoposide with midcycle vincristine versus standard chemotherapy in patients with small-cell lung cancer and good performance status: clinical and quality-of-life results of the British Medical Research Council multicenter randomized LU21 trial. J Clin Oncol. 2005 Nov 20;23(33):8371-9. [https://doi.org/10.1200/jco.2004.00.9969 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16293867/ PubMed] [https://clinicaltrials.gov/study/NCT00002822 NCT00002822] | ||
<!-- Presented in part (abstract and oral presentation) at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 13-17, 2005, and at the 11th World Conference on Lung Cancer, Barcelona, Spain, July 3-6, 2005. --> | <!-- Presented in part (abstract and oral presentation) at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 13-17, 2005, and at the 11th World Conference on Lung Cancer, Barcelona, Spain, July 3-6, 2005. --> | ||
− | # Hanna N, Bunn PA Jr, Langer C, Einhorn L, Guthrie T Jr, Beck T, Ansari R, Ellis P, Byrne M, Morrison M, Hariharan S, Wang B, Sandler A. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006 May 1;24(13):2038-43. [ | + | # Hanna N, Bunn PA Jr, Langer C, Einhorn L, Guthrie T Jr, Beck T, Ansari R, Ellis P, Byrne M, Morrison M, Hariharan S, Wang B, Sandler A. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006 May 1;24(13):2038-43. [https://doi.org/10.1200/jco.2005.04.8595 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16648503/ PubMed] |
− | # Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. [ | + | # '''GSK 104864-A/389:''' Eckardt JR, von Pawel J, Papai Z, Tomova A, Tzekova V, Crofts TE, Brannon S, Wissel P, Ross G. Open-label, multicenter, randomized, phase III study comparing oral topotecan/cisplatin versus etoposide/cisplatin as treatment for chemotherapy-naive patients with extensive-disease small-cell lung cancer. J Clin Oncol. 2006 May 1;24(13):2044-51. [https://doi.org/10.1200/JCO.2005.03.3332 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16648504/ PubMed] [https://clinicaltrials.gov/study/NCT00043927 NCT00043927] |
− | # Sun Y, Cheng Y, Hao X, Wang J, Hu C, Han B, Liu X, Zhang L, Wan H, Xia Z, Liu Y, Li W, Hou M, Zhang H, Xiu Q, Zhu Y, Feng J, Qin S, Luo X. Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer. BMC Cancer. 2016 Apr 9;16:265. [https:// | + | # '''JCOG 9702:''' Okamoto H, Watanabe K, Kunikane H, Yokoyama A, Kudoh S, Asakawa T, Shibata T, Kunitoh H, Tamura T, Saijo N. Randomised phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702. Br J Cancer. 2007 Jul 16;97(2):162-9. Epub 2007 Jun 19. [https://doi.org/10.1038/sj.bjc.6603810 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360311/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17579629/ PubMed] |
+ | # Baka S, Califano R, Ferraldeschi R, Aschroft L, Thatcher N, Taylor P, Faivre-Finn C, Blackhall F, Lorigan P. Phase III randomised trial of doxorubicin-based chemotherapy compared with platinum-based chemotherapy in small-cell lung cancer. Br J Cancer. 2008 Aug 5;99(3):442-7. [https://doi.org/10.1038/sj.bjc.6604480 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527803/ link to PMC article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18665190/ PubMed] | ||
+ | # '''SWOG S0124:''' Lara PN Jr, Natale R, Crowley J, Lenz HJ, Redman MW, Carleton JE, Jett J, Langer CJ, Kuebler JP, Dakhil SR, Chansky K, Gandara DR. Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124. J Clin Oncol. 2009 May 20;27(15):2530-5. Epub 2009 Apr 6. [https://doi.org/10.1200/JCO.2008.20.1061 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684855/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19349543/ PubMed] [https://clinicaltrials.gov/study/NCT00045162 NCT00045162] | ||
+ | # Zatloukal P, Cardenal F, Szczesna A, Gorbunova V, Moiseyenko V, Zhang X, Cisar L, Soria JC, Domine M, Thomas M. A multicenter international randomized phase III study comparing cisplatin in combination with irinotecan or etoposide in previously untreated small-cell lung cancer patients with extensive disease. Ann Oncol. 2010 Sep;21(9):1810-6. Epub 2010 Mar 15. [https://doi.org/10.1093/annonc/mdq036 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20231298/ PubMed] [https://clinicaltrials.gov/study/NCT00143455 NCT00143455] | ||
+ | # Baka S, Agelaki S, Kotsakis A, Veslemes M, Papakotoulas P, Agelidou M, Agelidou A, Tsaroucha E, Pavlakou G, Gerogianni A, Androulakis N, Vamvakas L, Kalbakis K, Mavroudis D, Georgoulias V. Phase III study comparing sequential versus alternate administration of cisplatin-etoposide and topotecan as first-line treatment in small cell lung cancer. Anticancer Res. 2010 Jul;30(7):3031-8. [https://ar.iiarjournals.org/content/30/7/3031.long link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20683051/ PubMed] | ||
+ | # '''SALUTE:''' Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. [https://doi.org/10.1200/JCO.2010.29.3423 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21502556/ PubMed] [https://clinicaltrials.gov/study/NCT00403403 NCT00403403] | ||
+ | # '''GSK 104864-A/479:''' Fink TH, Huber RM, Heigener DF, Eschbach C, Waller C, Steinhauer EU, Virchow JC, Eberhardt F, Schweisfurth H, Schroeder M, Ittel T, Hummler S, Banik N, Bogenrieder T, Acker T, Wolf M; “Aktion Bronchialkarzinom” (ABC Study Group). Topotecan/cisplatin compared with cisplatin/etoposide as first-line treatment for patients with extensive disease small-cell lung cancer: final results of a randomized phase III trial. J Thorac Oncol. 2012 Sep;7(9):1432-9. [https://doi.org/10.1097/jto.0b013e318260de75 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22895140/ PubMed] [https://clinicaltrials.gov/study/NCT00320359 NCT00320359] | ||
+ | # '''CALGB 30504:''' Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, Baggstrom M, Masters GA, Graziano SL, Crawford J, Bogart J, Vokes EE. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: A randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (Alliance). J Clin Oncol. 2015 May 20;33(15):1660-5. Epub 2015 Mar 2. [https://doi.org/10.1200/JCO.2014.57.3105 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429175/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25732163/ PubMed] [https://clinicaltrials.gov/study/NCT00453154 NCT00453154] | ||
+ | # '''D0750018:''' Sun Y, Cheng Y, Hao X, Wang J, Hu C, Han B, Liu X, Zhang L, Wan H, Xia Z, Liu Y, Li W, Hou M, Zhang H, Xiu Q, Zhu Y, Feng J, Qin S, Luo X. Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer. BMC Cancer. 2016 Apr 9;16:265. [https://doi.org/10.1186/s12885-016-2301-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826513/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27061082/ PubMed] [https://clinicaltrials.gov/study/NCT00660504 NCT00660504] | ||
+ | # '''COMBAT:''' Oh IJ, Kim KS, Park CK, Kim YC, Lee KH, Jeong JH, Kim SY, Lee JE, Shin KC, Jang TW, Lee HK, Lee KY, Lee SY. Belotecan/cisplatin versus etoposide/cisplatin in previously untreated patients with extensive-stage small cell lung carcinoma: a multi-center randomized phase III trial. BMC Cancer. 2016 Aug 26;16:690. [https://doi.org/10.1186/s12885-016-2741-z link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002146/ link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27566413/ PubMed] [https://clinicaltrials.gov/study/NCT00826644 NCT00826644] | ||
+ | # '''CA184-156:''' Reck M, Luft A, Szczesna A, Havel L, Kim SW, Akerley W, Pietanza MC, Wu YL, Zielinski C, Thomas M, Felip E, Gold K, Horn L, Aerts J, Nakagawa K, Lorigan P, Pieters A, Kong Sanchez T, Fairchild J, Spigel D. Phase III randomized trial of ipilimumab plus etoposide and platinum versus placebo plus etoposide and platinum in extensive-stage small-cell lung cancer. J Clin Oncol. 2016 Nov 1;34(31):3740-3748. [https://doi.org/10.1200/JCO.2016.67.6601 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27458307/ PubMed] [https://clinicaltrials.gov/study/NCT01450761 NCT01450761] | ||
+ | # '''GOIRC-AIFA FARM6PMFJM:''' Tiseo M, Boni L, Ambrosio F, Camerini A, Baldini E, Cinieri S, Brighenti M, Zanelli F, Defraia E, Chiari R, Dazzi C, Tibaldi C, Turolla GM, D'Alessandro V, Zilembo N, Trolese AR, Grossi F, Riccardi F, Ardizzoni A. Italian, multicenter, phase III, randomized study of cisplatin plus etoposide with or without bevacizumab as first-line treatment in extensive-disease small-cell lung cancer: the GOIRC-AIFA FARM6PMFJM trial. J Clin Oncol. 2017 Apr 20;35(12):1281-1287. Epub 2017 Jan 30. [https://doi.org/10.1200/JCO.2016.69.4844 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28135143/ PubMed] EudraCT 2007-007949-13 | ||
+ | # '''LUNGSTAR:''' Seckl MJ, Ottensmeier CH, Cullen M, Schmid P, Ngai Y, Muthukumar D, Thompson J, Harden S, Middleton G, Fife KM, Crosse B, Taylor P, Nash S, Hackshaw A. Multicenter, phase III, randomized, double-blind, placebo-controlled trial of pravastatin added to first-line standard chemotherapy in small-cell lung cancer (LUNGSTAR). J Clin Oncol. 2017 May 10;35(14):1506-1514. Epub 2017 Feb 27. [https://doi.org/10.1200/JCO.2016.69.7391 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28240967/ PubMed] [https://clinicaltrials.gov/study/NCT00433498 NCT00433498] | ||
+ | # '''CRCST-L-0001:''' Kim DW, Kim HG, Kim JH, Park K, Kim HK, Jang JS, Kim BS, Kang JH, Lee KH, Kim SW, Ryoo HM, Kim JS, Lee KH, Kwon JH, Choi JH, Shin SW, Hahn S, Heo DS. Randomized phase III trial of irinotecan plus cisplatin versus etoposide plus cisplatin in chemotherapy-naïve Korean patients with extensive-disease small cell lung cancer. Cancer Res Treat. 2019 Jan;51(1):119-127. Epub 2018 Mar 12. [https://doi.org/10.4143/crt.2018.019 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334001/ link to PMC article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29529858/ PubMed] [https://clinicaltrials.gov/study/NCT00349492 NCT00349492] | ||
+ | # '''KEYNOTE-604:''' Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gümüş M, Kato T, Kalemkerian GP, Luo Y, Ebiana V, Pietanza MC, Kim HR; KEYNOTE-604 Investigators. Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. J Clin Oncol. 2020 Jul 20;38(21):2369-2379. Epub 2020 May 29. [https://doi.org/10.1200/jco.20.00793 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32468956/ PubMed] [https://clinicaltrials.gov/study/NCT03066778 NCT03066778] | ||
+ | #'''RATIONALE-312:''' Cheng Y, Fan Y, Zhao Y, Huang D, Li X, Zhang P, Kang M, Yang N, Zhong D, Wang Z, Yu Y, Zhang Y, Zhao J, Qin T, Chen C, Leaw S, Zheng W, Song Y; RATIONALE-312 Study Group. Tislelizumab Plus Platinum and Etoposide Versus Placebo Plus Platinum and Etoposide as First-Line Treatment for Extensive-Stage SCLC (RATIONALE-312): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 3 Clinical Trial. J Thorac Oncol. 2024 Jul;19(7):1073-1085. Epub 2024 Mar 7. [https://doi.org/10.1016/j.jtho.2024.03.008 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/38460751/ PubMed] [https://clinicaltrials.gov/study/NCT04005716 NCT04005716] | ||
− | ==Cisplatin | + | ==Cisplatin & Etoposide (EP) & Bevacizumab {{#subobject:f451bd|Regimen=1}}== |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:3f85eb|Variant=1}}=== | ===Regimen {{#subobject:3f85eb|Variant=1}}=== | ||
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/JCO.2010.29.3423 Spigel et al. 2011 (SALUTE)] |
− | |style="background-color:# | + | |2007-2008 |
− | |[[#Cisplatin_.26_Etoposide_.28EP. | + | | style="background-color:#1a9851" |Randomized Phase 2 (E-esc) |
− | |style="background-color:# | + | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]] |
+ | | style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint)<br>Median PFS: 5.5 vs 4.4 mo<br>(HR 0.53, 95% CI 0.32-0.86) | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | ====Targeted therapy==== | ||
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | ||
− | |||
'''21-day cycle for 4 cycles''' | '''21-day cycle for 4 cycles''' | ||
− | + | </div> | |
− | '' | + | <div class="toccolours" style="background-color:#cbd5e7"> |
− | + | ====Subsequent treatment==== | |
+ | *[[#Bevacizumab_monotherapy|Bevacizumab]] maintenance | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''SALUTE:''' Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. [https://doi.org/10.1200/JCO.2010.29.3423 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21502556/ PubMed] [https://clinicaltrials.gov/study/NCT00403403 NCT00403403] | ||
+ | ==Cisplatin & Etoposide (EP) & Durvalumab {{#subobject:ddba26|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:3cbczd|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S0140-6736(19)32222-6 Paz-Ares et al. 2019 (CASPIAN)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-212-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2017-03-27 to 2018-05-29 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
+ | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]] | ||
+ | | style="background-color:#1a9850" |Superior OS<sup>1</sup> (primary endpoint)<br>Median OS: 12.9 vs 10.5 mo<br>(HR 0.75, 95% CI 0.62-0.91) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2021 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] as follows: | ||
+ | **Cycles 1 to 4: 75 to 80 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] as follows: | ||
+ | **Cycles 1 to 4: 80 to 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | ====Immunotherapy==== | ||
+ | *[[Durvalumab (Imfinzi)]] as follows: | ||
+ | **Cycles 1 to 4: 1500 mg IV once on day 1 | ||
+ | **Cycle 5 onwards: 1500 mg IV once on day 1 | ||
+ | '''21-day cycle for 4 cycles, then 28-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # '''CASPIAN:''' Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. Epub 2019 Oct 4. [https://doi.org/10.1016/S0140-6736(19)32222-6 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31590988/ PubMed] [https://clinicaltrials.gov/study/NCT03043872 NCT03043872] |
+ | ##'''PRO analysis:''' Goldman JW, Garassino MC, Chen Y, Özgüroğlu M, Dvorkin M, Trukhin D, Statsenko G, Hotta K, Ji JH, Hochmair MJ, Voitko O, Havel L, Poltoratskiy A, Losonczy G, Reinmuth N, Patel N, Laud PJ, Shire N, Jiang H, Paz-Ares L. Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study. Lung Cancer. 2020 Nov;149:46-52. Epub 2020 Sep 10. [https://doi.org/10.1016/j.lungcan.2020.09.003 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32961445/ PubMed] | ||
+ | ##'''Update:''' Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Każarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. Epub 2020 Dec 4. [https://doi.org/10.1016/s1470-2045(20)30539-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33285097/ PubMed] | ||
− | ==Cisplatin & | + | ==Cisplatin & Etoposide (EP) & Tislelizumab {{#subobject:icix26|Regimen=1}}== |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:ciszid|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/j.jtho.2024.03.008 Cheng et al. 2024 (RATIONALE-312)] | ||
+ | |2019-07-22 to 2021-04-21 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]] | ||
+ | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 15.5 vs 13.5 mo<br>(HR 0.75, 95% CI 0.61-0.93) | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] as follows: | ||
+ | **Cycles 1 to 4: 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] as follows: | ||
+ | **Cycles 1 to 4: 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | ====Immunotherapy==== | ||
+ | *[[Tislelizumab (Baizean)]] 200 mg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''RATIONALE-312:''' Cheng Y, Fan Y, Zhao Y, Huang D, Li X, Zhang P, Kang M, Yang N, Zhong D, Wang Z, Yu Y, Zhang Y, Zhao J, Qin T, Chen C, Leaw S, Zheng W, Song Y; RATIONALE-312 Study Group. Tislelizumab Plus Platinum and Etoposide Versus Placebo Plus Platinum and Etoposide as First-Line Treatment for Extensive-Stage SCLC (RATIONALE-312): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 3 Clinical Trial. J Thorac Oncol. 2024 Jul;19(7):1073-1085. Epub 2024 Mar 7. [https://doi.org/10.1016/j.jtho.2024.03.008 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/38460751/ PubMed] [https://clinicaltrials.gov/study/NCT04005716 NCT04005716] | ||
+ | |||
+ | ==Cisplatin & Irinotecan (IC) {{#subobject:277dbd|Regimen=1}}== | ||
IP: '''<u>I</u>'''rinotecan, '''<u>P</u>'''latinol (Cisplatin) | IP: '''<u>I</u>'''rinotecan, '''<u>P</u>'''latinol (Cisplatin) | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ===Regimen #1 {{#subobject:dc3fe1|Variant=1}}=== | + | ===Regimen variant #1, 30/65 {{#subobject:dc3fe1|Variant=1}}=== |
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2005.04.8595 Hanna et al. 2006] |
− | |style="background-color:# | + | |2000-2003 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
− | |style="background-color:# | + | |[[#Cisplatin_.26_Etoposide_.28EP.29_3|Cisplatin & Etoposide]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8 | *[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1 & 8 | *[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[:Category:Granulocyte colony-stimulating factors|G-CSF]] used according to 1999 American Society of Clinical Oncology guidelines |
− | *[[ | ||
*"Erythropoietin was allowed at the discretion of the treating physician." | *"Erythropoietin was allowed at the discretion of the treating physician." | ||
− | |||
'''21-day cycle for 4 cycles; additional cycles could be given at physician discretion''' | '''21-day cycle for 4 cycles; additional cycles could be given at physician discretion''' | ||
− | + | </div></div><br> | |
− | ===Regimen #2 {{#subobject:c0be38|Variant=1}}=== | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| | + | ===Regimen variant #2, 60/60 {{#subobject:c0be38|Variant=1}}=== |
− | | | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Study |
− | | | + | !style="width: 20%"|Dates of enrollment |
− | |[[Levels_of_Evidence#Efficacy| | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/NEJMoa003034 Noda et al. 2002 (JCOG 9511)] | ||
+ | |1995-1998 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
+ | |[[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]] | ||
+ | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 12.8 vs 9.4 mo<br>(HR 0.60, 95% CI 0.43-0.83) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684855/ Lara et al. 2009 (SWOG S0124)] | ||
+ | |2002-2007 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
+ | |[[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/JCO.2013.53.5153 Satouchi et al. 2014 (JCOG 0509)] |
− | |style="background-color:# | + | |2007-2010 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#Amrubicin_.26_Cisplatin_999|Amrubicin & Cisplatin]] |
+ | | style="background-color:#1a9850" |Superior OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Irinotecan (Camptosar)]] 60 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | *[[Irinotecan (Camptosar)]] 60 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*"Hydration and administration of antiemetic drugs." | *"Hydration and administration of antiemetic drugs." | ||
− | |||
'''28-day cycle for 4 cycles''' | '''28-day cycle for 4 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #3, 80/65 {{#subobject:dcf04b|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1093/annonc/mdq036 Zatloukal et al. 2010] | ||
+ | |2003-2007 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
+ | |[[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]] | ||
+ | | style="background-color:#eeee01" |Non-inferior OS (primary endpoint)<br>Median OS: 10.2 vs 9.7 mo<br>(HR 0.81, 95% CI 0.65-1.01) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: this dosing was the result of a mid-protocol amendment.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | '''21-day cycle for 6 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, Fukuoka M, Mori K, Watanabe K, Tamura T, Yamamoto S, Saijo N; | + | # '''JCOG 9511:''' Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, Fukuoka M, Mori K, Watanabe K, Tamura T, Yamamoto S, Saijo N; [[Study_Groups#JCOG|JCOG]]. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):85-91. [https://doi.org/10.1056/NEJMoa003034 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11784874/ PubMed] |
<!-- Presented in part (abstract and oral presentation) at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 13-17, 2005, and at the 11th World Conference on Lung Cancer, Barcelona, Spain, July 3-6, 2005. --> | <!-- Presented in part (abstract and oral presentation) at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 13-17, 2005, and at the 11th World Conference on Lung Cancer, Barcelona, Spain, July 3-6, 2005. --> | ||
− | # Hanna N, Bunn PA Jr, Langer C, Einhorn L, Guthrie T Jr, Beck T, Ansari R, Ellis P, Byrne M, Morrison M, Hariharan S, Wang B, Sandler A. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006 May 1;24(13):2038-43. [ | + | # Hanna N, Bunn PA Jr, Langer C, Einhorn L, Guthrie T Jr, Beck T, Ansari R, Ellis P, Byrne M, Morrison M, Hariharan S, Wang B, Sandler A. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006 May 1;24(13):2038-43. [https://doi.org/10.1200/jco.2005.04.8595 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16648503/ PubMed] |
− | + | # '''SWOG S0124:''' Lara PN Jr, Natale R, Crowley J, Lenz HJ, Redman MW, Carleton JE, Jett J, Langer CJ, Kuebler JP, Dakhil SR, Chansky K, Gandara DR. Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124. J Clin Oncol. 2009 May 20;27(15):2530-5. Epub 2009 Apr 6. [https://doi.org/10.1200/JCO.2008.20.1061 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684855/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19349543/ PubMed] [https://clinicaltrials.gov/study/NCT00045162 NCT00045162] | |
− | ==Docetaxel | + | # Zatloukal P, Cardenal F, Szczesna A, Gorbunova V, Moiseyenko V, Zhang X, Cisar L, Soria JC, Domine M, Thomas M. A multicenter international randomized phase III study comparing cisplatin in combination with irinotecan or etoposide in previously untreated small-cell lung cancer patients with extensive disease. Ann Oncol. 2010 Sep;21(9):1810-6. Epub 2010 Mar 15. [https://doi.org/10.1093/annonc/mdq036 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20231298/ PubMed] [https://clinicaltrials.gov/study/NCT00143455 NCT00143455] |
− | + | <!-- Presented in part at the 49th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 4, 2013. --> | |
− | + | # '''JCOG 0509:''' Satouchi M, Kotani Y, Shibata T, Ando M, Nakagawa K, Yamamoto N, Ichinose Y, Ohe Y, Nishio M, Hida T, Takeda K, Kimura T, Minato K, Yokoyama A, Atagi S, Fukuda H, Tamura T, Saijo N. Phase III study comparing amrubicin plus cisplatin with irinotecan plus cisplatin in the treatment of extensive-disease small-cell lung cancer: JCOG 0509. J Clin Oncol. 2014 Apr 20;32(12):1262-8. Epub 2014 Mar 17. [https://doi.org/10.1200/JCO.2013.53.5153 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24638015/ PubMed] UMIN000000720 | |
− | + | ==Docetaxel monotherapy {{#subobject:46f6bb|Regimen=1}}== | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:57c4cc|Variant=1}}=== | ===Regimen {{#subobject:57c4cc|Variant=1}}=== | ||
− | {| | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | | | + | !style="width: 33%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://pubmed.ncbi.nlm.nih.gov/10439170 Hesketh et al. 1999] |
− | |style="background-color:# | + | |Not reported in abstract |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over | + | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1 |
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Hesketh PJ, Crowley JJ, Burris HA 3rd, Williamson SK, Balcerzak SP, Peereboom D, Goodwin JW, Gross HM, Moore DF Jr, Livingston RB, Gandara DR. Evaluation of docetaxel in previously untreated extensive-stage small cell lung cancer: a Southwest Oncology Group phase II trial. Cancer J Sci Am. 1999 Jul-Aug;5(4):237-41. ''' | + | # Hesketh PJ, Crowley JJ, Burris HA 3rd, Williamson SK, Balcerzak SP, Peereboom D, Goodwin JW, Gross HM, Moore DF Jr, Livingston RB, Gandara DR; [[Study_Groups#SWOG|SWOG]]. Evaluation of docetaxel in previously untreated extensive-stage small cell lung cancer: a Southwest Oncology Group phase II trial. Cancer J Sci Am. 1999 Jul-Aug;5(4):237-41. '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10439170/ PubMed] |
− | == | + | ==EP-Topotecan {{#subobject:ept0cd|Regimen=1}}== |
− | {| class="wikitable" style=" | + | EP-Topotecan: '''<u>E</u>'''toposide and '''<u>P</u>'''latinol (Cisplatin), followed by Topotecan |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:da93c4|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.3816/clc.2005.n.034 Ignatiadis et al. 2005] | ||
+ | |2000-2003 | ||
+ | |style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cisplatin_.26_Etoposide_.28EP.29.2FTopotecan_monotherapy_999|EP/Topotecan]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, EP portion (cycles 1 to 4)==== | ||
+ | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | ====Chemotherapy, Topotecan portion (cycles 5 to 8)==== | ||
+ | *[[Topotecan (Hycamtin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
+ | '''21-day cycle for 8 cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Ignatiadis M, Mavroudis D, Veslemes M, Boukovinas J, Syrigos K, Agelidou M, Agelidou A, Gerogianni A, Pavlakou G, Tselepatiotis E, Nikolakopoulos J, Georgoulias V; Hellenic Oncology Research Group. Sequential versus alternating administration of cisplatin/etoposide and topotecan as first-line treatment in extensive-stage small-cell lung cancer: preliminary results of a Phase III Trial of the Hellenic Oncology Research Group. Clin Lung Cancer. 2005 Nov;7(3):183-9. [https://doi.org/10.3816/clc.2005.n.034 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16354313/ PubMed] | ||
+ | |||
+ | ==Ifosfamide monotherapy {{#subobject:d04316|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:3276f5|Variant=1}}=== | ===Regimen {{#subobject:3276f5|Variant=1}}=== | ||
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 17%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 15%"|Dates of enrollment |
− | | | + | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence# | + | !style="width: 17%"|Comparator |
− | |[[Levels_of_Evidence#Toxicity| | + | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | |rowspan=2|[ | + | | rowspan="2" |[https://doi.org/10.1016/s0169-5002(02)00074-0 Ettinger et al. 2002 (ECOG E1588)] |
− | |rowspan=2 style="background-color:# | + | |rowspan=2|1988-1990 |
− | |[[ | + | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
− | |style="background-color:# | + | |1. [[Small_cell_lung_cancer_-_historical#CAV_2|CAV]] |
− | |style="background-color:# | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS |
+ | | style="background-color:#1a9851" |Less toxic | ||
|- | |- | ||
− | |[[ | + | |2. [[#Teniposide_monotherapy|Teniposide]] |
− | |style="background-color:# | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS |
− | |style="background-color:#d3d3d3"|Not reported | + | | style="background-color:#d3d3d3" |Not reported |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 5 | *[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Mesna (Mesnex)]] 300 mg/m<sup>2</sup> IV three times per day on days 1 to 5, '''given 0, 4, and 8 hours after each dose of ifosfamide''' (total dose per cycle: 4500 mg/m<sup>2</sup>) |
− | *[[Mesna (Mesnex)]] 300 mg/m<sup>2</sup> | ||
− | |||
'''21-day cycle for 4 to 6 cycles''' | '''21-day cycle for 4 to 6 cycles''' | ||
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | + | ====Subsequent treatment==== | |
− | + | *ECOG E1588, patients with CR: [[#Ifosfamide_monotherapy|Ifosfamide]] continuation x 2 cycles, then prophylactic [[#Whole_brain_irradiation_2|whole-brain irradiation]] if still in CR | |
− | + | *ECOG E1588, patients with PR: [[#Ifosfamide_monotherapy|Ifosfamide]] continuation until progression of disease, then salvage [[#Cisplatin_.26_Etoposide_.28EP.29_4|EP]] | |
− | + | </div></div> | |
− | |||
===References=== | ===References=== | ||
− | # Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; | + | # '''ECOG E1588:''' Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; [[Study_Groups#ECOG|ECOG]]. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. [https://doi.org/10.1016/s0169-5002(02)00074-0 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12234701/ PubMed] |
− | == | + | ==IVE {{#subobject:d04tr2|Regimen=1}}== |
− | {| class="wikitable" style=" | + | IVE: '''<u>I</u>'''fosfamide, '''<u>V</u>'''P-16 (Etoposide), '''<u>E</u>'''pirubicin |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:32qeb5|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5610723/ Berghmans et al. 2017 (ELCWP 01994)] | ||
+ | |2000-2013 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | ''Note: This combination is based on a commonly used backbone in Europe. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | *[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Mesna (Mesnex)]] 300 mg/m<sup>2</sup> IV once on day 1, '''given just before ifosfamide''', then 300 mg/m<sup>2</sup> IV once every 4 hours for 72 hours (total dose per cycle: 5700 mg/m<sup>2</sup>) | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''ELCWP 01994:''' Berghmans T, Scherpereel A, Meert AP, Giner V, Lecomte J, Lafitte JJ, Leclercq N, Paesmans M, Sculier JP; European Lung Cancer Working Party (ELCWP). A Phase III Randomized Study Comparing a Chemotherapy with Cisplatin and Etoposide to a Etoposide Regimen without Cisplatin for Patients with Extensive Small-Cell Lung Cancer. Front Oncol. 2017 Sep 19;7:217. [https://doi.org/10.3389/fonc.2017.00217 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5610723/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28975084/ PubMed] [https://clinicaltrials.gov/study/NCT00658580 NCT00658580] | ||
+ | ==Teniposide monotherapy {{#subobject:60479c|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:964e45|Variant=1}}=== | ===Regimen {{#subobject:964e45|Variant=1}}=== | ||
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 17%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 15%"|Dates of enrollment |
− | | | + | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence# | + | !style="width: 17%"|Comparator |
− | |[[Levels_of_Evidence#Toxicity| | + | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | |rowspan=2|[ | + | | rowspan="2" |[https://doi.org/10.1016/s0169-5002(02)00074-0 Ettinger et al. 2002 (ECOG E1588)] |
− | |rowspan=2 style="background-color:# | + | |rowspan=2|1988-1990 |
− | |[[ | + | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
− | |style="background-color:# | + | |1. [[Small_cell_lung_cancer_-_historical#CAV_2|CAV]] |
− | |style="background-color:# | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS |
+ | | style="background-color:#1a9851" |Less toxic | ||
|- | |- | ||
− | |[[ | + | |2. [[#Ifosfamide_monotherapy|Ifosfamide]] |
− | |style="background-color:# | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS |
− | |style="background-color:#d3d3d3"|Not reported | + | | style="background-color:#d3d3d3" |Not reported |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Teniposide (Vumon)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 5 | *[[Teniposide (Vumon)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
− | |||
'''21-day cycle for 4 to 6 cycles''' | '''21-day cycle for 4 to 6 cycles''' | ||
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | + | ====Subsequent treatment==== | |
− | + | *ECOG E1588, patients with CR after 4 to 6 cycles: [[#Teniposide_monotherapy|Teniposide]] continuation x 2 cycles | |
− | + | *ECOG E1588, patients with CR after 6 to 8 cycles: [[#Whole_brain_irradiation_2|prophylactic whole-brain irradiation]] | |
− | + | *ECOG E1588, patients with PR: [[#Teniposide_monotherapy|Teniposide]] continuation until progression of disease, then salvage [[#Cisplatin_.26_Etoposide_.28EP.29_4|EP]] | |
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; | + | # '''ECOG E1588:''' Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; [[Study_Groups#ECOG|ECOG]]. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. [https://doi.org/10.1016/s0169-5002(02)00074-0 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12234701/ PubMed] |
− | == | + | =Extensive stage, consolidation after first-line therapy= |
− | {| class="wikitable" style=" | + | ==Whole brain irradiation {{#subobject:37efe7|Regimen=1}}== |
+ | PCI: '''<u>P</u>'''rophylactic '''<u>C</u>'''ranial '''<u>I</u>'''rradiation | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:b0bc9a|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/s0169-5002(02)00074-0 Ettinger et al. 2002 (ECOG E1588)] |
− | | | + | |1988-1990 |
− | = | + | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT |
− | + | | style="background-color:#d3d3d3" | | |
− | | | + | | style="background-color:#d3d3d3" | |
− | | | ||
− | | | ||
− | |||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1056/NEJMoa071780 Slotman et al. 2007 (EORTC 22993)] |
− | |style="background-color:# | + | |2001-2006 |
− | | | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | |style="background-color:# | + | |[[Small_cell_lung_cancer_-_null_regimens#Observation_2|Observation]] |
+ | | style="background-color:#1a9850" |Superior OS (secondary endpoint)<br>Median OS: 6.7 vs 5.4 mo<br>(HR 0.68, 95% CI 0.52-0.88) | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | *[[ | + | ====Preceding treatment==== |
− | + | *ECOG E1588: [[Small_cell_lung_cancer_-_historical#CAV_2|CAV]] versus [[#Ifosfamide_monotherapy|Ifosfamide]] versus [[#Teniposide_monotherapy|Teniposide]] | |
− | *[[ | + | *EORTC 22993: [[Regimen_classes#Chemotherapy-based_regimen|Chemotherapy]] x 4 to 6 cycles (regimen not specified) |
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | + | ====Radiotherapy==== | |
− | + | *[[External beam radiotherapy|Whole brain irradiation]] by one of the following: 2000 cGy in 5 or 8 fractions, 2400 cGy in 12 fractions, 2500 cGy in 10 fractions, or 3000 cGy in 10 or 12 fractions | |
− | + | '''1- to 3-week course''' | |
− | == | + | </div></div> |
− | |||
− | |||
− | ==== | ||
− | |||
− | |||
− | |||
− | '' | ||
− | |||
===References=== | ===References=== | ||
− | # | + | # '''Meta-analysis:''' Aupérin A, Arriagada R, Pignon JP, Le Péchoux C, Gregor A, Stephens RJ, Kristjansen PE, Johnson BE, Ueoka H, Wagner H, Aisner J; Prophylactic Cranial Irradiation Overview Collaborative Group. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med. 1999 Aug 12;341(7):476-84. [https://doi.org/10.1056/NEJM199908123410703 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10441603/ PubMed] |
− | + | # '''ECOG E1588:''' Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; [[Study_Groups#ECOG|ECOG]]. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. [https://doi.org/10.1016/s0169-5002(02)00074-0 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12234701/ PubMed] | |
− | = | + | # '''EORTC 22993:''' Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, Postmus P, Collette L, Musat E, Senan S; [[Study_Groups#EORTC|EORTC]] Radiation Oncology Group; [[Study_Groups#EORTC|EORTC]] Lung Cancer Group. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007 Aug 16;357(7):664-72. [https://doi.org/10.1056/NEJMoa071780 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17699816/ PubMed] [https://clinicaltrials.gov/study/NCT00016211 NCT00016211] |
− | + | =Extensive stage, maintenance after first-line therapy= | |
− | ==Bevacizumab | + | ==Bevacizumab monotherapy {{#subobject:e2a180|Regimen=1}}== |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:60322b|Variant=1}}=== | ===Regimen {{#subobject:60322b|Variant=1}}=== | ||
− | {| | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | | | + | !style="width: 33%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/JCO.2010.29.3423 Spigel et al. 2011 (SALUTE)] |
− | |style="background-color:# | + | |2007-2008 |
+ | | style="background-color:#91cf61" |Non-randomized part of phase 2 RCT | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | ==== | + | ====Preceding treatment==== |
+ | *[[#Carboplatin_.26_Etoposide_.28CE.29_.26_Bevacizumab|CE & Bevacizumab]] induction x 4 or [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Bevacizumab|EP & Bevacizumab]] induction x 4 | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
+ | ===References=== | ||
+ | # Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. [https://doi.org/10.1200/JCO.2010.29.3423 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21502556/ PubMed] [https://clinicaltrials.gov/study/NCT00403403 NCT00403403] | ||
+ | ==Ipilimumab monotherapy {{#subobject:492277|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:be9690|Variant=1}}=== | ||
+ | {| class="wikitable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1093/annonc/mds213 Reck et al. 2012 (CA184-041<sub>SCLC</sub>)] | ||
+ | |2008-2009 | ||
+ | | style="background-color:#91cf61" |Non-randomized part of phase 2 RCT | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Ipilimumab|Carboplatin, Paclitaxel, Ipilimumab]] induction | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Immunotherapy==== | ||
+ | *[[Ipilimumab (Yervoy)]] 10 mg/kg IV once on day 1 | ||
+ | '''12-week cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # '''CA184-041<sub>SCLC</sub>:''' Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Lu H, Cuillerot JM, Lynch TJ. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol. 2013 Jan;24(1):75-83. Epub 2012 Aug 2. [https://doi.org/10.1093/annonc/mds213 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22858559/ PubMed] [https://clinicaltrials.gov/study/NCT00527735 NCT00527735] |
− | + | ==Sunitinib monotherapy {{#subobject:fa7428|Regimen=1}}== | |
− | = | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | + | ===Regimen {{#subobject:957c3e|Variant=1}}=== | |
− | == | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | {| class="wikitable" style=" | + | !style="width: 20%"|Study |
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429175/ Ready et al. 2015 (CALGB 30504)] | ||
+ | |2007-2011 | ||
+ | | style="background-color:#1a9851" |Randomized Phase 2 (E-esc) | ||
+ | |[[Small_cell_lung_cancer_-_null_regimens#Observation_2|Observation]] | ||
+ | | style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint)<br>Median PFS: 3.7 vs 2.1 mo<br>(HR 0.62, 95% CI 0.38-0.98) | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[#Carboplatin_.26_Etoposide_.28CE.29_2|Carboplatin & Etoposide]] or [[#Cisplatin_.26_Etoposide_.28EP.29_3|Cisplatin & Etoposide]] for 4 to 6 cycles | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Sunitinib (Sutent)]] as follows: | ||
+ | **Cycle 1: 150 mg PO once on day 1, then 37.5 mg PO once per day on days 2 to 28 | ||
+ | **Cycle 2 onwards: 37.5 mg PO once per day on days 1 to 28 | ||
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''CALGB 30504:''' Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, Baggstrom M, Masters GA, Graziano SL, Crawford J, Bogart J, Vokes EE. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: A randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (Alliance). J Clin Oncol. 2015 May 20;33(15):1660-5. Epub 2015 Mar 2. [https://doi.org/10.1200/JCO.2014.57.3105 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429175/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25732163/ PubMed] [https://clinicaltrials.gov/study/NCT00453154 NCT00453154] | ||
+ | |||
+ | =Relapsed or refractory disease, second-line= | ||
+ | ==Amrubicin monotherapy {{#subobject:35370b|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:514e41|Variant=1}}=== | ===Regimen {{#subobject:514e41|Variant=1}}=== | ||
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2013.54.5392 von Pawel et al. 2014 (ACT-1)] |
− | |style="background-color:# | + | |2007-2010 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
− | |style="background-color:# | + | |[[#Topotecan_monotherapy|Topotecan]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 7.5 vs 7.8 mo<br>(HR 0.88, 95% CI 0.73-1.06) | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/j.annonc.2021.01.071 Spigel et al. 2021 (CheckMate 331)] | ||
+ | |2015-2017 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[Small_cell_lung_cancer_-_historical#Nivolumab_monotherapy_2|Nivolumab]] | ||
+ | | style="background-color:#fee08b" |Might have inferior OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Amrubicin (Calsed)]] 40 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1 to 3 | *[[Amrubicin (Calsed)]] 40 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1 to 3 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*"Prophylactic antibiotics were recommended for patients at high risk of infectious complications." | *"Prophylactic antibiotics were recommended for patients at high risk of infectious complications." | ||
− | + | '''21-day cycle for at least 6 cycles''' | |
− | '''21-day cycle for | + | </div></div> |
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
<!-- Presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011, and 14th World Conference on Lung Cancer, Amsterdam, the Netherlands, July 3-7, 2011. --> | <!-- Presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011, and 14th World Conference on Lung Cancer, Amsterdam, the Netherlands, July 3-7, 2011. --> | ||
− | # von Pawel J, Jotte R, Spigel DR, O'Brien ME, Socinski MA, Mezger J, Steins M, Bosquée L, Bubis J, Nackaerts K, Trigo JM, Clingan P, Schütte W, Lorigan P, Reck M, Domine M, Shepherd FA, Li S, Renschler MF. Randomized | + | # '''ACT-1:''' von Pawel J, Jotte R, Spigel DR, O'Brien ME, Socinski MA, Mezger J, Steins M, Bosquée L, Bubis J, Nackaerts K, Trigo JM, Clingan P, Schütte W, Lorigan P, Reck M, Domine M, Shepherd FA, Li S, Renschler MF. Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. J Clin Oncol. 2014 Dec 10;32(35):4012-9. Epub 2014 Nov 10. [https://doi.org/10.1200/jco.2013.54.5392 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25385727/ PubMed] [https://clinicaltrials.gov/study/NCT00547651 NCT00547651] |
+ | # '''CheckMate 331:''' Spigel DR, Vicente D, Ciuleanu TE, Gettinger S, Peters S, Horn L, Audigier-Valette C, Pardo Aranda N, Juan-Vidal O, Cheng Y, Zhang H, Shi M, Luft A, Wolf J, Antonia S, Nakagawa K, Fairchild J, Baudelet C, Pandya D, Doshi P, Chang H, Reck M. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331. Ann Oncol. 2021 May;32(5):631-641. Epub 2021 Feb 1. [https://doi.org/10.1016/j.annonc.2021.01.071 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33539946/ PubMed] [https://clinicaltrials.gov/study/NCT02481830 NCT02481830] | ||
− | == | + | ==Carboplatin & Etoposide (CE) {{#subobject:dobzc6|Regimen=1}}== |
− | {| class="wikitable" style=" | + | EC: '''<u>E</u>'''toposide & '''<u>C</u>'''arboplatin |
+ | <br>EP: '''<u>E</u>'''toposide & '''<u>P</u>'''araplatin (Carboplatin) | ||
+ | <br>CE: '''<u>C</u>'''arboplatin & '''<u>E</u>'''toposide | ||
+ | <br>Ca/E: '''<u>Ca</u>'''rboplatin & '''<u>E</u>'''toposide | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:8ac106|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s1470-2045(20)30461-7 Baize et al. 2020 (GFPC 01-2013)] | ||
+ | |2013-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
+ | |[[#Topotecan_monotherapy|Topotecan]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 4.7 vs 2.7 mo<br>(HR 0.57, 90% CI 0.41-0.73) | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | '''21-day cycle for 6 cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''GFPC 01-2013:''' Baize N, Monnet I, Greillier L, Geier M, Lena H, Janicot H, Vergnenegre A, Crequit J, Lamy R, Auliac JB, Letreut J, Le Caer H, Gervais R, Dansin E, Madroszyk A, Renault PA, Le Garff G, Falchero L, Berard H, Schott R, Saulnier P, Chouaid C; Groupe Français de Pneumo-Cancérologie. Carboplatin plus etoposide versus topotecan as second-line treatment for patients with sensitive relapsed small-cell lung cancer: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2020 Sep;21(9):1224-1233. [https://doi.org/10.1016/s1470-2045(20)30461-7 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32888454/ PubMed] [https://clinicaltrials.gov/study/NCT02738346 NCT02738346] | ||
− | ===Regimen=== | + | ==Cisplatin, Etoposide, Irinotecan {{#subobject:11d584|Regimen=1}}== |
− | {| | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | | | + | ===Regimen {{#subobject:e7a275|Variant=1}}=== |
− | |[[Levels_of_Evidence#Evidence| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Dates of enrollment |
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/S1470-2045(16)30104-8 Goto et al. 2016 (JCOG0605)] |
− | |style="background-color:# | + | |2007-2012 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | |style="background-color:# | + | |[[#Topotecan_monotherapy|Topotecan]] |
+ | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 18.2 vs 12.5 mo<br>(HR 0.67, 90% CI 0.51-0.88) | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | '' | + | ====Chemotherapy==== |
− | + | *[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 8 | |
+ | *[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 3 | ||
+ | *[[Irinotecan (Camptosar)]] 90 mg/m<sup>2</sup> IV over 90 minutes once on day 8 | ||
+ | ====Supportive therapy==== | ||
+ | *[[:Category:Granulocyte colony-stimulating factors|G-CSF]], started on cycle 1 day 9: (dose not specified) SC once per day, continued throughout except for days of chemotherapy | ||
+ | '''14-day cycle for 5 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | # '''JCOG0605:''' Goto K, Ohe Y, Shibata T, Seto T, Takahashi T, Nakagawa K, Tanaka H, Takeda K, Nishio M, Mori K, Satouchi M, Hida T, Yoshimura N, Kozuki T, Imamura F, Kiura K, Okamoto H, Sawa T, Tamura T; JCOG. Combined chemotherapy with cisplatin, etoposide, and irinotecan versus topotecan alone as second-line treatment for patients with sensitive relapsed small-cell lung cancer (JCOG0605): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1147-57. Epub 2016 Jun 14. [https://doi.org/10.1016/S1470-2045(16)30104-8 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27312053/ PubMed] UMIN000000828 | |
− | |||
− | == | + | ==Lurbinectedin monotherapy {{#subobject:7167f3|Regimen=1}}== |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:bef45d|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/s1470-2045(20)30068-1 Trigo et al. 2020 (PM1183-B-005-14)] |
− | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | |
− | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-221-1 <span style="color:white;">ESMO-MCBS (2)</span>]''' | |
− | |||
− | {| | ||
− | |''' | ||
− | |||
− | |||
− | |||
|- | |- | ||
− | | | + | |} --> |
− | |style="background-color:# | + | |2015-2019 |
− | | | + | | style="background-color:#91cf61" |Phase 2 (RT) |
− | + | |ORR: 35.2% (95% CI, 26.2-45.2%) | |
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Lurbinectedin (Zepzelca)]] 3.2 mg/m<sup>2</sup> IV over 60 minutes once on day 1 |
− | * | + | ====Supportive therapy==== |
− | + | *"All patients received antiemetic prophylaxis." | |
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''PM1183-B-005-14:''' Trigo J, Subbiah V, Besse B, Moreno V, López R, Sala MA, Peters S, Ponce S, Fernández C, Alfaro V, Gómez J, Kahatt C, Zeaiter A, Zaman K, Boni V, Arrondeau J, Martínez M, Delord JP, Awada A, Kristeleit R, Olmedo ME, Wannesson L, Valdivia J, Rubio MJ, Anton A, Sarantopoulos J, Chawla SP, Mosquera-Martinez J, D'Arcangelo M, Santoro A, Villalobos VM, Sands J, Paz-Ares L. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020 May;21(5):645-654. [https://doi.org/10.1016/s1470-2045(20)30068-1 link to original article] '''dosing details in manuscript have been reviewed by our editors''' Epub 2020 Mar 27. [https://pubmed.ncbi.nlm.nih.gov/32224306/ PubMed] [https://clinicaltrials.gov/study/NCT02454972 NCT02454972] | ||
− | = | + | =Relapsed or refractory disease, subsequent lines= |
− | + | ''This section includes studies that do not specify an exact line or have yet to be categorized.'' | |
− | '''21-day cycles, | + | ==Bendamustine monotherapy {{#subobject:6ed7fe|Regimen=1}}== |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:35da2b|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 80%; text-align:center;" | ||
+ | !style="width: 25%"|Study | ||
+ | !style="width: 25%"|Dates of enrollment | ||
+ | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990869/ Lammers et al. 2014 (VICC THO 0920)] | ||
+ | |2009-2012 | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | |ORR: 33% (95% CI, 14-52%) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Bendamustine]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2 | ||
+ | '''21-day cycle for up to 6 cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''VICC THO 0920:''' Lammers PE, Shyr Y, Li CI, Hutchison AS, Sandler A, Carbone DP, Johnson DH, Keedy VL, Horn L. Phase II study of bendamustine in relapsed chemotherapy sensitive or resistant small-cell lung cancer. J Thorac Oncol. 2014 Apr;9(4):559-62. [https://doi.org/10.1097/jto.0000000000000079 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990869/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24736081/ PubMed] [https://clinicaltrials.gov/study/NCT00984542 NCT00984542] | ||
− | '' | + | ==CAV {{#subobject:d3d3e|Regimen=1}}== |
− | + | CAV: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine | |
− | ===Regimen # | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| | + | ===Regimen variant #1, no capping {{#subobject:1ugcbf|Variant=1}}=== |
− | | | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Study |
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/s2213-2600(22)00309-5 Aix et al. 2022 (ATLANTIS)] |
− | |style="background-color:# | + | |2016-2018 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Doxorubicin_.26_Lurbinectedin_999|Doxorubicin & Lurbinectedin]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 7.6 vs 8.6 mo<br>(HR 1.03, 95% CI 0.87-1.22) | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1 | ||
− | *[[Vincristine (Oncovin)]] | + | *[[Vincristine (Oncovin)]] 2 mg IV once on day 1 |
− | + | '''21-day cycle for up to 10 cycles''' | |
− | '''21-day cycle for | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | === | + | ===Regimen variant #2, capped {{#subobject:83cdbf|Variant=1}}=== |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 20%"|Study | |
− | + | !style="width: 20%"|Dates of enrollment | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | + | !style="width: 20%"|Comparator | |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.1999.17.2.658 von Pawel et al. 1999] | ||
+ | |Not reported | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[Small_cell_lung_cancer#Topotecan_monotherapy|Topotecan]] | ||
+ | | style="background-color:#ffffbf" |Did not meet co-primary endpoints of ORR/DOR | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | ''Note: von Pawel et al. 1999 does not clearly state the duration of each cycle, but 21 days is used in other CAV regimens, and there was no information in the paper that contradicted this.'' | |
− | ===Regimen {{#subobject: | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | {| | + | ====Chemotherapy==== |
− | | | + | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> (maximum dose of 2000 mg) (route not specified) once on day 1 |
− | |[[Levels_of_Evidence#Evidence| | + | *[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> (maximum dose of 100 mg) IV once on day 1 |
+ | *[[Vincristine (Oncovin)]] 2 mg IV once on day 1 | ||
+ | ====Supportive therapy==== | ||
+ | *[[:Category:Granulocyte colony-stimulating factors|G-CSF]] use per physician discretion | ||
+ | '''21-day cycle for up to 6 cycles beyond maximal response''' | ||
+ | ''Patients with stable disease after 4 cycles could have treatment discontinued at physician discretion.'' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #3 {{#subobject:531cce|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1200/jco.1994.12.10.2022 Ihde et al. 1994] |
− | |style="background-color:# | + | |1983-1991 |
+ | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | ||
|- | |- | ||
|} | |} | ||
− | ''Note: this | + | ''Note: Ihde et al. 1994 did not specifically say that the three medications were all given on day 1, but this is assumed to be the case based on other CAV regimens.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[#Cisplatin_.26_Etoposide_.28EP.29_2|EP]]; standard-dose versus [[#Cisplatin_.26_Etoposide_.28EP.29|EP]]; high-dose, with progression | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Doxorubicin (Adriamycin)]] | + | *[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1 |
− | *[[ | + | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 |
+ | '''21-day cycle for 4 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # Ihde DC, Mulshine JL, Kramer BS, Steinberg SM, Linnoila RI, Gazdar AF, Edison M, Phelps RM, Lesar M, Phares JC, Grayson J, Minna JD, Johnson BE. Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. J Clin Oncol. 1994 Oct;12(10):2022-34. [https://doi.org/10.1200/jco.1994.12.10.2022 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/7931470/ PubMed] |
+ | # von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, Stewart DJ, Clark PI, Palmer MC, Depierre A, Carmichael J, Krebs JB, Ross G, Lane SR, Gralla R. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999 Feb;17(2):658-67. [https://doi.org/10.1200/jco.1999.17.2.658 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10080612/ PubMed] | ||
+ | #'''ATLANTIS:''' Aix SP, Ciuleanu TE, Navarro A, Cousin S, Bonanno L, Smit EF, Chiappori A, Olmedo ME, Horvath I, Grohé C, Farago AF, López-Vilariño JA, Cullell-Young M, Nieto A, Vasco N, Gómez J, Kahatt C, Zeaiter A, Carcereny E, Roubec J, Syrigos K, Lo G, Barneto I, Pope A, Sánchez A, Kattan J, Zarogoulidis K, Waller CF, Bischoff H, Juan-Vidal O, Reinmuth N, Dómine M, Paz-Ares L. Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial. Lancet Respir Med. 2023 Jan;11(1):74-86. Epub 2022 Oct 14. [https://doi.org/10.1016/s2213-2600(22)00309-5 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/36252599/ PubMed] [https://clinicaltrials.gov/study/NCT02566993 NCT02566993] | ||
==Cisplatin & Etoposide (EP) {{#subobject:eb644a|Regimen=1}}== | ==Cisplatin & Etoposide (EP) {{#subobject:eb644a|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | EP: '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin) |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:159cb4|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1002/1097-0142(19900215)65:4%3C856::AID-CNCR2820650404%3E3.0.CO;2-6 O'Bryan et al. 1990 (SWOG S8215)] |
− | + | |Not reported | |
− | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | |
− | + | |[[Stub#BTOC|BTOC]] | |
− | + | | style="background-color:#ffffbf" |Did not meet efficacy endpoints | |
− | |||
− | | | ||
− | |[[ | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/s0169-5002(02)00074-0 Ettinger et al. 2002 (ECOG E1588)] |
− | |style="background-color:# | + | |1988-1990 |
+ | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | + | ====Preceding treatment==== | |
+ | *ECOG E1588: [[Small_cell_lung_cancer_-_historical#CAV_2|CAV]] versus [[#Ifosfamide_monotherapy|ifosfamide]] versus [[#Teniposide_monotherapy|teniposide]], with progression | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; | + | # '''SWOG S8215:''' O'Bryan RM, Crowley JJ, Kim PN, Epstein RB, Neilan B, Coltman CA Jr, Stuckey WJ, Pazdur R. Comparison of etoposide and cisplatin with bis-chloro-ethylnitrosourea, thiotepa, vincristine, and cyclophosphamide for salvage treatment in small cell lung cancer: a Southwest Oncology Group Study. Cancer. 1990 Feb 15;65(4):856-60. [https://doi.org/10.1002/1097-0142(19900215)65:4%3C856::AID-CNCR2820650404%3E3.0.CO;2-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2153435/ PubMed] |
+ | # '''ECOG E1588:''' Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; [[Study_Groups#ECOG|ECOG]]. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. [https://doi.org/10.1016/s0169-5002(02)00074-0 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12234701/ PubMed] | ||
− | == | + | ==Docetaxel monotherapy {{#subobject:5918ce|Regimen=1}}== |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:a6b72f|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" | |
− | + | !style="width: 33%"|Study | |
− | ===Regimen {{#subobject: | + | !style="width: 33%"|Dates of enrollment |
− | {| | + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | | | ||
− | |[[Levels_of_Evidence#Evidence| | ||
− | |||
− | |||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/0959-8049(94)90455-3 Smyth et al. 1994] |
− | | | + | |Not reported |
− | + | | style="background-color:#91cf61" |Phase 2 | |
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1 |
− | + | '''21-day cycles''' | |
− | + | </div></div> | |
− | |||
− | |||
− | |||
− | |||
− | ''' | ||
− | |||
===References=== | ===References=== | ||
− | # | + | # Smyth JF, Smith IE, Sessa C, Schoffski P, Wanders J, Franklin H, Kaye SB; Early Clinical Trials Group of the EORTC. Activity of docetaxel (Taxotere) in small cell lung cancer. Eur J Cancer. 1994;30A(8):1058-60. [https://doi.org/10.1016/0959-8049(94)90455-3 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/7654428/ PubMed] |
− | == | + | ==Epirubicin & Ifosfamide {{#subobject:3661d7|Regimen=1}}== |
− | + | EI: '''<u>E</u>'''pirubicin, '''<u>I</u>'''fosfamide | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:c74edb|Variant=1}}=== | |
− | + | {| class="wikitable" style="width: 60%; text-align:center;" | |
− | ===Regimen {{#subobject: | + | !style="width: 33%"|Study |
− | {| | + | !style="width: 33%"|Dates of enrollment |
− | | | + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence#Evidence| | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/j.lungcan.2011.07.012 Jacot et al. 2012] |
− | |style="background-color:# | + | |1992-2010 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 1 |
− | + | *[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 & 2 | |
− | ''' | + | ====Supportive therapy==== |
− | + | *[[Mesna (Mesnex)]] (dose/route/schedule not specified) on days 1 & 2 | |
+ | *[[:Category:Granulocyte colony-stimulating factors|G-CSF]] use per physician discretion | ||
+ | '''28-day cycle for up to 6 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # Jacot W, Pujol JL, Chakra M, Molinier O, Bozonnat MC, Gervais R, Quantin X. Epirubicin and ifosfamide in relapsed or refractory small cell lung cancer patients. Lung Cancer. 2012 Feb;75(2):213-6. Epub 2011 Aug 9. [https://doi.org/10.1016/j.lungcan.2011.07.012 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21831476/ PubMed] |
− | + | ==Etoposide monotherapy {{#subobject:4ae4d4|Regimen=1}}== | |
− | ==Etoposide | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |||
− | |||
− | |||
− | |||
===Regimen {{#subobject:4970d7|Variant=1}}=== | ===Regimen {{#subobject:4970d7|Variant=1}}=== | ||
− | {| | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | | | + | !style="width: 33%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://pubmed.ncbi.nlm.nih.gov/2154857 Einhorn et al. 1990] |
− | |style="background-color:# | + | |Not reported in abstract |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.1990.8.10.1613 Johnson et al. 1990] |
− | |style="background-color:# | + | |1988-07 to 1990-01 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> PO once per day, taken | + | *[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> PO once per day on days 1 to 21, taken on an empty stomach |
− | + | '''21-day cycles''' | |
− | + | </div></div> | |
− | |||
− | |||
− | '''21-day cycles | ||
− | |||
===References=== | ===References=== | ||
− | # Einhorn LH, Pennington K, McClean J. Phase II trial of daily oral VP-16 in refractory small cell lung cancer: a Hoosier Oncology Group study. Semin Oncol. 1990 Feb;17(1 Suppl 2):32-5. '''Not available online; abstract contains protocol''' [https:// | + | # Einhorn LH, Pennington K, McClean J; Hoosier Oncology Group. Phase II trial of daily oral VP-16 in refractory small cell lung cancer: a Hoosier Oncology Group study. Semin Oncol. 1990 Feb;17(1 Suppl 2):32-5. '''Not available online; abstract contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/2154857/ PubMed] |
− | # Johnson DH, Greco FA, Strupp J, Hande KR, Hainsworth JD. Prolonged administration of oral etoposide in patients with relapsed or refractory small-cell lung cancer: a phase II trial. J Clin Oncol. 1990 Oct;8(10):1613-7. [ | + | # Johnson DH, Greco FA, Strupp J, Hande KR, Hainsworth JD. Prolonged administration of oral etoposide in patients with relapsed or refractory small-cell lung cancer: a phase II trial. J Clin Oncol. 1990 Oct;8(10):1613-7. [https://doi.org/10.1200/jco.1990.8.10.1613 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2170589/ PubMed] |
− | ==Gemcitabine | + | ==Gemcitabine monotherapy {{#subobject:9a9c65|Regimen=1}}== |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, 5 cycles {{#subobject:5efd8c|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1023/a:1011104509759 van der Lee et al. 2001] | ||
+ | |1997-02 to 1998-11 | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
− | |||
|} | |} | ||
− | ===Regimen {{#subobject: | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | {| | + | ====Chemotherapy==== |
− | | | + | *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15 |
− | |[[Levels_of_Evidence#Evidence| | + | '''28-day cycle for up to 5 cycles''' |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #2, indefinite {{#subobject:5a9c6c|Variant=1}}=== | |
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2003.09.130 Masters et al. 2003 (ECOG E1597)] |
− | |style="background-color:# | + | |1997-12-05 to 1998-09-04 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: dose escalation was carried out if patients had less than grade 2 toxicity with cycle 1.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> | + | *[[Gemcitabine (Gemzar)]] as follows: |
− | ** | + | **Cycle 1: 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15 |
− | + | **Cycle 2 onwards: 1250 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15 | |
− | '''28-day | + | '''28-day cycles''' |
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # van der Lee I, Smit EF, van Putten JW, Groen HJ, Schlösser NJ, Postmus PE, Schramel FM. Single-agent gemcitabine in patients with resistant small-cell lung cancer. Ann Oncol. 2001 Apr;12(4):557-61. [ | + | # van der Lee I, Smit EF, van Putten JW, Groen HJ, Schlösser NJ, Postmus PE, Schramel FM. Single-agent gemcitabine in patients with resistant small-cell lung cancer. Ann Oncol. 2001 Apr;12(4):557-61. [https://doi.org/10.1023/a:1011104509759 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11398892/ PubMed] |
− | # Masters GA, Declerck L, Blanke C, Sandler A, DeVore R, Miller K, Johnson D; | + | # '''ECOG E1597:''' Masters GA, Declerck L, Blanke C, Sandler A, DeVore R, Miller K, Johnson D; [[Study_Groups#ECOG|ECOG]]. Phase II trial of gemcitabine in refractory or relapsed small-cell lung cancer: Eastern Cooperative Oncology Group Trial 1597. J Clin Oncol. 2003 Apr 15;21(8):1550-5. [https://doi.org/10.1200/jco.2003.09.130 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12697880/ PubMed] |
− | + | ==Ifosfamide monotherapy {{#subobject:a1f3a|Regimen=1}}== | |
− | ==Ifosfamide | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |||
− | |||
− | |||
− | |||
===Regimen {{#subobject:d82a3f|Variant=1}}=== | ===Regimen {{#subobject:d82a3f|Variant=1}}=== | ||
− | {| | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | | | + | !style="width: 33%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/0277-5379(88)90242-8 Cantwell et al. 1988] |
− | |style="background-color:# | + | |Not reported |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Ifosfamide (Ifex)]] 5000 mg/m<sup>2</sup> IV once on day 1 | *[[Ifosfamide (Ifex)]] 5000 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*[[Mesna (Mesnex)]] 5000 mg/m<sup>2</sup> IV once on day 1 | *[[Mesna (Mesnex)]] 5000 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Cantwell BM, Bozzino JM, Corris P, Harris AL. The multidrug resistant phenotype in clinical practice; evaluation of cross resistance to ifosfamide and mesna after VP16-213, doxorubicin and vincristine (VPAV) for small cell lung cancer. Eur J Cancer Clin Oncol. 1988 Feb;24(2):123-9. [ | + | # Cantwell BM, Bozzino JM, Corris P, Harris AL. The multidrug resistant phenotype in clinical practice; evaluation of cross resistance to ifosfamide and mesna after VP16-213, doxorubicin and vincristine (VPAV) for small cell lung cancer. Eur J Cancer Clin Oncol. 1988 Feb;24(2):123-9. [https://doi.org/10.1016/0277-5379(88)90242-8 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2833398/ PubMed] |
− | # '''Review:''' Marangolo M, Giovanis P. Ifosfamide in small cell lung cancer. Oncology. 2003;65 Suppl 2:46-9. Review. [ | + | # '''Review:''' Marangolo M, Giovanis P. Ifosfamide in small cell lung cancer. Oncology. 2003;65 Suppl 2:46-9. Review. [https://doi.org/10.1159/000073358 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14586147/ PubMed] |
− | + | ==Ifosfamide & Paclitaxel {{#subobject:6540a2|Regimen=1}}== | |
− | ==Ifosfamide & | + | PI: '''<u>P</u>'''aclitaxel, '''<u>I</u>'''fosfamide |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:8e22a|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/j.lungcan.2007.05.022 Park et al. 2007a] | ||
+ | |2002-10 to 2006-03 | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | + | ====Chemotherapy==== | |
− | ===Regimen {{#subobject: | + | *[[Ifosfamide (Ifex)]] 2500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 2 |
− | {| | + | *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1 |
− | | | + | ====Supportive therapy==== |
− | |[[Levels_of_Evidence#Evidence| | + | *[[Mesna (Mesnex)]] 500 mg/m<sup>2</sup> IV three times per day on days 1 & 2, '''given 15 minutes before, 4 hours after, and 8 hours after ifosfamide''' (total dose per cycle: 3000 mg/m<sup>2</sup>) |
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Park S, Ahn MJ, Ahn JS, Lee J, Hong YS, Park BB, Lee SC, Hwang IG, Park JO, Lim H, Kang WK, Park K. Combination chemotherapy with paclitaxel and ifosfamide as the third-line regimen in patients with heavily pretreated small cell lung cancer. Lung Cancer. 2007 Oct;58(1):116-22. Epub 2007 Jul 12. [https://doi.org/10.1016/j.lungcan.2007.05.022 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17624473/ PubMed] | ||
+ | ==Irinotecan monotherapy {{#subobject:344d89|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, weekly {{#subobject:c0a7e0|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.1992.10.8.1225 Masuda et al. 1992] |
− | |style="background-color:# | + | |Not reported |
+ | | style="background-color:#ffffbe" |Phase 2, fewer than 20 pts | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Irinotecan (Camptosar)]] 100 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1, 8, 15 |
− | + | ====Supportive therapy==== | |
− | + | *No routine prophylaxis against diarrhea, nausea, or vomiting used. | |
− | ====Supportive | + | '''21-day cycles''' |
− | * | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #2, q3wk {{#subobject:cu88e0|Variant=1}}=== | |
− | ''' | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | + | !style="width: 20%"|Study | |
− | === | + | !style="width: 20%"|Dates of enrollment |
− | # | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | + | !style="width: 20%"|Comparator | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
− | {| class="wikitable" style=" | ||
|- | |- | ||
− | |[ | + | |rowspan=2|[https://doi.org/10.1016/j.lungcan.2022.03.003 Edelman et al. 2022 (DISTINCT)] |
− | | | + | |rowspan=2|2017 to not reported |
− | + | |rowspan=2 style="background-color:#1a9851" |Phase 3 (C) | |
− | + | |1. [[#Irinotecan_.26_Dinutuximab_999|Irinotecan & Dinutuximab]] | |
− | | | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 7 vs 6.9 mo |
− | |[[ | ||
|- | |- | ||
− | |[ | + | |2. [[#Topotecan_monotherapy|Topotecan]] |
− | |style="background-color:# | + | | style="background-color:#d3d3d3" |Not reported |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Irinotecan (Camptosar)]] | + | *[[Irinotecan (Camptosar)]] 350 mg/m<sup>2</sup> IV once on day 1 |
− | + | '''21-day cycles''' | |
− | + | </div></div> | |
− | |||
===References=== | ===References=== | ||
− | # Masuda N, Fukuoka M, Kusunoki Y, Matsui K, Takifuji N, Kudoh S, Negoro S, Nishioka M, Nakagawa K, Takada M. CPT-11: a new derivative of camptothecin for the treatment of refractory or relapsed small-cell lung cancer. J Clin Oncol. 1992 Aug;10(8):1225-9. [ | + | # Masuda N, Fukuoka M, Kusunoki Y, Matsui K, Takifuji N, Kudoh S, Negoro S, Nishioka M, Nakagawa K, Takada M. CPT-11: a new derivative of camptothecin for the treatment of refractory or relapsed small-cell lung cancer. J Clin Oncol. 1992 Aug;10(8):1225-9. [https://doi.org/10.1200/jco.1992.10.8.1225 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/1321891/ PubMed] |
+ | #'''DISTINCT:''' Edelman MJ, Dvorkin M, Laktionov K, Navarro A, Juan-Vidal O, Kozlov V, Golden G, Jordan O, Deng CQ, Bentsion D, Chouaid C, Dechev H, Dowlati A, Fernández Núñez N, Ivashchuk O, Kiladze I, Kortua T, Leighl N, Luft A, Makharadze T, Min Y, Quantin X; DISTINCT study investigators. Randomized phase 3 study of the anti-disialoganglioside antibody dinutuximab and irinotecan vs irinotecan or topotecan for second-line treatment of small cell lung cancer. Lung Cancer. 2022 Apr;166:135-142. Epub 2022 Mar 4. [https://doi.org/10.1016/j.lungcan.2022.03.003 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35278766/ PubMed] [https://clinicaltrials.gov/study/NCT03098030 NCT03098030] | ||
− | ==Paclitaxel | + | ==Paclitaxel monotherapy {{#subobject:e71ce6|Regimen=1}}== |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #1, every 3 weeks {{#subobject:dbac57|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" | |
− | + | !style="width: 33%"|Study | |
− | ===Regimen #1, every 3 weeks {{#subobject:dbac57|Variant=1}}=== | + | !style="width: 33%"|Dates of enrollment |
− | {| | + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | | | ||
− | |[[Levels_of_Evidence#Evidence| | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151229/ Smit et al. 1998] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151229/ Smit et al. 1998] | ||
− | |style="background-color:# | + | |1994-12 to 1996-06 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> | + | *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1 |
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Dexamethasone (Decadron)]] 8 mg PO given twice on day 1; 12 and 6 hours prior to paclitaxel |
− | *[[Dexamethasone (Decadron)]] 8 mg PO given twice | + | *[[Clemastine (Tavist)]] 2 mg IV push once on day 1; 30 minutes prior to paclitaxel |
− | *[[Clemastine ( | ||
*One of the following H2 blockers: | *One of the following H2 blockers: | ||
− | **[[Cimetidine (Tagamet)]] 300 mg IV push once 30 minutes prior to paclitaxel | + | **[[Cimetidine (Tagamet)]] 300 mg IV push once on day 1; 30 minutes prior to paclitaxel |
− | **[[Ranitidine (Zantac)]] 50 mg IV push once 30 minutes prior to paclitaxel | + | **[[Ranitidine (Zantac)]] 50 mg IV push once on day 1; 30 minutes prior to paclitaxel |
− | + | '''21-day cycle for up to 5 cycles''' | |
− | '''21-day cycle for up to 5 cycles | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ===Regimen #2, weekly paclitaxel {{#subobject:658a5f|Variant=1}}=== | + | ===Regimen variant #2, weekly paclitaxel {{#subobject:658a5f|Variant=1}}=== |
− | {| | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | | | + | !style="width: 33%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://ar.iiarjournals.org/content/26/1B/777.long Yamamoto et al. 2006] |
− | |style="background-color:# | + | |1999-12 to 2002-02 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV over | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36 |
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Dexamethasone (Decadron)]] 20 mg IV once per day on days 1, 8, 15, 22, 29, 36; 30 minutes prior to paclitaxel |
− | *[[Dexamethasone (Decadron)]] 20 mg IV once 30 minutes prior to paclitaxel | + | *[[Ranitidine (Zantac)]] 50 mg IV once per day on days 1, 8, 15, 22, 29, 36; 30 minutes prior to paclitaxel |
− | *[[Ranitidine (Zantac)]] 50 mg IV once 30 minutes prior to paclitaxel | + | *[[Diphenhydramine (Benadryl)]] 50 mg IV once per day on days 1, 8, 15, 22, 29, 36; 30 minutes prior to paclitaxel |
− | *[[Diphenhydramine (Benadryl)]] 50 mg IV once 30 minutes prior to paclitaxel | + | *If ANC less than 1000/μL or WBC count less than 2 x 10<sup>9</sup>/L, [[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 2 mcg/kg SC once per day is given until WBC count more than or equal to 10 x 10<sup>9</sup>/L, except on days that paclitaxel is given |
− | *If ANC | ||
− | |||
'''8-week cycles''' | '''8-week cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Smit EF, Fokkema E, Biesma B, Groen HJ, Snoek W, Postmus PE. A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer. Br J Cancer. 1998;77(2):347-51. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151229/ link to PMC article] | + | # Smit EF, Fokkema E, Biesma B, Groen HJ, Snoek W, Postmus PE. A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer. Br J Cancer. 1998;77(2):347-51. [https://doi.org/10.1038/bjc.1998.54 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151229/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/9461009/ PubMed] |
− | # Yamamoto N, Tsurutani J, Yoshimura N, Asai G, Moriyama A, Nakagawa K, Kudoh S, Takada M, Minato Y, Fukuoka M. Phase II study of weekly paclitaxel for relapsed and refractory small cell lung cancer. Anticancer Res. 2006 Jan-Feb;26(1B):777-81. [ | + | # Yamamoto N, Tsurutani J, Yoshimura N, Asai G, Moriyama A, Nakagawa K, Kudoh S, Takada M, Minato Y, Fukuoka M. Phase II study of weekly paclitaxel for relapsed and refractory small cell lung cancer. Anticancer Res. 2006 Jan-Feb;26(1B):777-81. [https://ar.iiarjournals.org/content/26/1B/777.long link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16739353/ PubMed] |
− | + | ==Tarlatamab monotherapy {{#subobject:6hw324|Regimen=1}}== | |
− | == | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style=" | + | ===Regimen {{#subobject:abc285|Variant=1}}=== |
+ | {| class="wikitable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa2307980 Ahn et al. 2023 (DeLLphi-301)] | ||
+ | |2021-12 to 2023-05 | ||
+ | | style="background-color:#91cf61" |Phase 2 (RT) | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
+ | ====Immunotherapy==== | ||
+ | *[[Tarlatamab (Imdelltra)]] as follows: | ||
+ | **Cycle 1: 1 mg IV over 60 minutes once on day 1, then 10 mg IV once on day 8 | ||
+ | **Cycle 2 onwards: 10 mg IV once on day 1 | ||
+ | '''14-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''DeLLphi-301:''' Ahn MJ, Cho BC, Felip E, Korantzis I, Ohashi K, Majem M, Juan-Vidal O, Handzhiev S, Izumi H, Lee JS, Dziadziuszko R, Wolf J, Blackhall F, Reck M, Bustamante Alvarez J, Hummel HD, Dingemans AC, Sands J, Akamatsu H, Owonikoko TK, Ramalingam SS, Borghaei H, Johnson ML, Huang S, Mukherjee S, Minocha M, Jiang T, Martinez P, Anderson ES, Paz-Ares L; DeLLphi-301 Investigators. Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. N Engl J Med. 2023 Nov 30;389(22):2063-2075. Epub 2023 Oct 20. [https://doi.org/10.1056/nejmoa2307980 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37861218/ PubMed] [https://clinicaltrials.gov/study/NCT05060016 NCT05060016] | ||
− | ===Regimen {{#subobject: | + | ==Temozolomide monotherapy {{#subobject:693cf4|Regimen=1}}== |
− | {| | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | | | + | ===Regimen variant #1, 75 mg/m<sup>2</sup>/d, 21 out of 28 days {{#subobject:96a285|Variant=1}}=== |
− | |[[Levels_of_Evidence#Evidence| | + | {| class="wikitable" style="width: 60%; text-align:center;" |
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1158/1078-0432.CCR-11-2059 Pietanza et al. 2012] |
− | |style="background-color:# | + | |2008-2010 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Temozolomide (Temodar)]] 75 mg/m<sup>2</sup> PO once per day on days 1 to 21 (no food within 2 hours before or 1 hour after temozolomide) |
− | + | ====Supportive therapy==== | |
− | + | *[[Ondansetron (Zofran)]] 8 mg PO once per day on days 1 to 21, taken prior to temozolomide prn nausea | |
− | ====Supportive | + | *Patients with at least grade 3 lymphopenia received prophylaxis for Pneumocystis carinii pneumonia (no specific medication/dose/schedule listed) |
− | *[[ | + | '''28-day cycles''' |
− | + | </div></div><br> | |
− | ''' | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | + | ===Regimen variant #2, 200 mg/m<sup>2</sup>/d, 5 out of 28 days {{#subobject:792fd1|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" | |
− | + | !style="width: 33%"|Study | |
− | + | !style="width: 33%"|Dates of enrollment | |
− | + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | |||
− | |||
− | |||
− | |||
− | ===Regimen # | ||
− | {| | ||
− | | | ||
− | |[[Levels_of_Evidence#Evidence| | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497567/ Zauderer et al. 2014] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497567/ Zauderer et al. 2014 (MSKCC 08-065)] |
− | |style="background-color:# | + | |Not reported |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> PO once per day on days 1 to 5 | *[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> PO once per day on days 1 to 5 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Ondansetron (Zofran)]] 8 mg PO once per day on days 1 to 5; 30 minutes prior to temozolomide |
− | *[[Ondansetron (Zofran)]] 8 mg PO once 30 minutes prior to | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Pietanza MC, Kadota K, Huberman K, Sima CS, Fiore JJ, Sumner DK, Travis WD, Heguy A, Ginsberg MS, Holodny AI, Chan TA, Rizvi NA, Azzoli CG, Riely GJ, Kris MG, Krug LM. Phase II trial of temozolomide in patients with relapsed sensitive or refractory small cell lung cancer, with assessment of methylguanine-DNA methyltransferase as a potential biomarker. Clin Cancer Res. 2012 Feb 15;18(4):1138-45. Epub 2012 Jan 6. [https://doi.org/10.1158/1078-0432.CCR-11-2059 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22228633/ PubMed] | ||
+ | # '''MSKCC 08-065:''' Zauderer MG, Drilon A, Kadota K, Huberman K, Sima CS, Bergagnini I, Sumner DK, Travis WD, Heguy A, Ginsberg MS, Holodny AI, Riely GJ, Kris MG, Krug LM, Pietanza MC. Trial of a 5-day dosing regimen of temozolomide in patients with relapsed small cell lung cancers with assessment of methylguanine-DNA methyltransferase. Lung Cancer. 2014 Nov;86(2):237-40. Epub 2014 Aug 17. [https://doi.org/10.1016/j.lungcan.2014.08.007 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25194640/ PubMed] [https://clinicaltrials.gov/study/NCT00740636 NCT00740636] | ||
− | ===Regimen #2 {{#subobject: | + | ==Topotecan monotherapy {{#subobject:6e9625|Regimen=1}}== |
− | {| | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | | | + | ===Regimen variant #1, 1 mg/m<sup>2</sup> {{#subobject:a060a6|Variant=1}}=== |
− | |[[Levels_of_Evidence#Evidence| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/S1470-2045(16)30104-8 Goto et al. 2016 (JCOG0605)] |
− | |style="background-color:# | + | |2007-2012 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Cisplatin.2C_Etoposide.2C_Irinotecan|Cisplatin, Etoposide, Irinotecan]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Topotecan (Hycamtin)]] 1 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5 |
− | + | '''21-day cycle for 4 cycles''' | |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #2, 1.5 mg/m<sup>2</sup> {{#subobject:a08066|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | ''' | + | !style="width: 20%"|Study |
− | + | !style="width: 20%"|Dates of enrollment | |
− | === | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | # | + | !style="width: 20%"|Comparator |
− | # | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | + | |- | |
− | = | + | |[https://doi.org/10.1200/jco.1999.17.2.658 von Pawel et al. 1999] |
− | + | |Not reported | |
+ | | style="background-color:#1a9851" |Phase 3 (E-RT-de-esc) | ||
+ | |[[Small_cell_lung_cancer_-_historical#CAV_3|CAV]] | ||
+ | | style="background-color:#ffffbf" |Did not meet co-primary endpoints of ORR/DOR | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2006.08.3998 Eckardt et al. 2007] | ||
+ | |1999-2001 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Topotecan_monotherapy|Topotecan]]; oral | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2013.54.5392 von Pawel et al. 2014 (ACT-1)] | ||
+ | |2007-2010 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Amrubicin_monotherapy|Amrubicin]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.annonc.2021.01.071 Spigel et al. 2021 (CheckMate 331)] |
− | + | |2015-2017 | |
− | + | | style="background-color:#1a9851" |Phase 3 (C) | |
− | + | |[[Small_cell_lung_cancer_-_historical#Nivolumab_monotherapy_2|Nivolumab]] | |
− | | | + | | style="background-color:#fee08b" |Might have inferior OS |
− | |[[ | ||
− | | | ||
− | |||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/s2213-2600(22)00309-5 Aix et al. 2022 (ATLANTIS)] |
− | |style="background-color:# | + | |2016-2018 |
− | |[[# | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#Doxorubicin_.26_Lurbinectedin|Doxorubicin & Lurbinectedin]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 7.6 vs 8.6 mo<br>(HR 1.03, 95% CI 0.87-1.22) | ||
|- | |- | ||
− | | | + | |[https://doi.org/10.1016/j.jtho.2021.02.009 Blackhall et al. 2021 (TAHOE)] |
− | + | |2017-04-11 to 2018-12-07 | |
− | + | | style="background-color:#1a9851" |Phase 3 (C) | |
− | + | |[[#Rovalpituzumab_tesirine_monotherapy_999|Rovalpituzumab tesirine]] | |
− | + | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 8.6 vs 6.3 mo<br>(HR 0.68, 95% CI 0.55-0.85) | |
− | |||
− | |||
− | |||
− | | | ||
− | |[[ | ||
− | | | ||
− | |||
|- | |- | ||
− | |[ | + | |rowspan=2|[https://doi.org/10.1016/j.lungcan.2022.03.003 Edelman et al. 2022 (DISTINCT)] |
− | |style="background-color:# | + | |rowspan=2|2017 to not reported |
− | |[[ | + | |rowspan=2 style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |1. [[#Irinotecan_.26_Dinutuximab_999|Irinotecan & Dinutuximab]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 7.4 vs 6.9 mo | ||
|- | |- | ||
− | |[ | + | |2. [[#Irinotecan_monotherapy|Irinotecan]] |
− | + | | style="background-color:#d3d3d3" |Not reported | |
− | |||
− | |style="background-color:# | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.23.02110 Spigel et al. 2024 (RESILIENT Par 2)] |
− | |style="background-color:# | + | |2019-08 to 2021-02 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#Irinotecan_liposome_monotherapy_999|Liposomal irinotecan]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 8.3 vs 7.9 mo<br>(HR 0.90, 95% CI 0.73-1.11) | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Topotecan (Hycamtin)]] 1.5 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5 | *[[Topotecan (Hycamtin)]] 1.5 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*(varies depending on reference): | *(varies depending on reference): | ||
− | *[[ | + | *[[:Category:Granulocyte colony-stimulating factors|G-CSF]] use per physician discretion |
*In von Pawel et al. 2014 (ACT-1), "Prophylactic antibiotics were recommended for patients at high risk of infectious complications." | *In von Pawel et al. 2014 (ACT-1), "Prophylactic antibiotics were recommended for patients at high risk of infectious complications." | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | ''Duration varies depending on reference:'' | |
− | ''Duration varies depending on reference: | ||
*In von Pawel et al. 1999 treatment is given until progression of disease, unacceptable toxicity, or 6 cycles beyond maximal response. Patients with stable disease after 4 cycles could have treatment discontinued at physician discretion. | *In von Pawel et al. 1999 treatment is given until progression of disease, unacceptable toxicity, or 6 cycles beyond maximal response. Patients with stable disease after 4 cycles could have treatment discontinued at physician discretion. | ||
*In Eckardt et al. 2007, patients with complete or partial response continued treatment progression of disease or 2 cycles beyond best response. Patients with stable disease received at least 4 cycles therapy. | *In Eckardt et al. 2007, patients with complete or partial response continued treatment progression of disease or 2 cycles beyond best response. Patients with stable disease received at least 4 cycles therapy. | ||
− | *In | + | *In ACT-1, treatment was given for 6 cycles or until progression of disease. Patients who had at least stable disease by cycle 6 could receive another 6 cycles of treatment. |
− | + | </div></div><br> | |
− | ===Regimen #3, oral route {{#subobject:cb27be|Variant=1}}=== | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| | + | ===Regimen variant #3, oral route {{#subobject:cb27be|Variant=1}}=== |
− | | | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Study |
− | | | + | !style="width: 20%"|Dates of enrollment |
− | |[[Levels_of_Evidence#Efficacy|' | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2006.08.3998 Eckardt et al. 2007] | ||
+ | |1999-2001 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
+ | |[[#Topotecan_monotherapy|Topotecan]]; IV (1.5 mg/m<sup>2</sup>) | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2006.06.5821 O'Brien et al. 2006 (GSK 104864/478)] | ||
+ | |2000-2004 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |[[Small_cell_lung_cancer_-_null_regimens#Best_supportive_care|Best supportive care]] | ||
+ | | style="background-color:#91cf60" |Seems to have superior OS (primary endpoint) | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/s1470-2045(20)30461-7 Baize et al. 2020 (GFPC 01-2013)] |
− | |style="background-color:# | + | |2013-2018 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#Carboplatin_.26_Etoposide_.28CE.29_3|Carboplatin & Etoposide]] |
+ | | style="background-color:#d73027" |Inferior PFS | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.annonc.2021.01.071 Spigel et al. 2021 (CheckMate 331)] |
− | |style="background-color:# | + | |2015-2017 |
− | | | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[Small_cell_lung_cancer_-_historical#Nivolumab_monotherapy_2|Nivolumab]] |
+ | | style="background-color:#fee08b" |Might have inferior OS | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: Duration of treatment details vary depending on reference. In GSK 104864/478, treatment is given for at least 4 cycles, though this depended on tolerability and response. In Eckardt et al. 2007, patients with complete or partial response continued treatment progression of disease or 2 cycles beyond best response. Patients with stable disease received at least 4 cycles of therapy. Patients enrolled in GFPC 01-2013 received 6 cycles.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Topotecan (Hycamtin)]] 2.3 mg/m<sup>2</sup> PO once per day on days 1 to 5 | *[[Topotecan (Hycamtin)]] 2.3 mg/m<sup>2</sup> PO once per day on days 1 to 5 | ||
− | + | '''21-day cycle for varying durations: indefinitely (GFPC 01-2013); 4 or more cycles (see note)''' | |
− | '''21-day | + | </div></div> |
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
− | # von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, Stewart DJ, Clark PI, Palmer MC, Depierre A, Carmichael J, Krebs JB, Ross G, Lane SR, Gralla R. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999 Feb;17(2):658-67. [ | + | # von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, Stewart DJ, Clark PI, Palmer MC, Depierre A, Carmichael J, Krebs JB, Ross G, Lane SR, Gralla R. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999 Feb;17(2):658-67. [https://doi.org/10.1200/jco.1999.17.2.658 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10080612/ PubMed] |
<!-- Presented in part at the International Association for the Study of Lung Cancer’s 11th World Conference on Lung Cancer, Barcelona, Spain, July 3-6, 2005. --> | <!-- Presented in part at the International Association for the Study of Lung Cancer’s 11th World Conference on Lung Cancer, Barcelona, Spain, July 3-6, 2005. --> | ||
− | # O'Brien ME, Ciuleanu TE, Tsekov H, Shparyk Y, Cuceviá B, Juhasz G, Thatcher N, Ross GA, Dane GC, Crofts T. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol. 2006 Dec 1;24(34):5441-7. [ | + | # '''GSK 104864/478:''' O'Brien ME, Ciuleanu TE, Tsekov H, Shparyk Y, Cuceviá B, Juhasz G, Thatcher N, Ross GA, Dane GC, Crofts T. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol. 2006 Dec 1;24(34):5441-7. [https://doi.org/10.1200/jco.2006.06.5821 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17135646/ PubMed] [https://clinicaltrials.gov/study/NCT00276276 NCT00276276] |
<!-- Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31 to June 3, 2003. --> | <!-- Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31 to June 3, 2003. --> | ||
− | # Eckardt JR, von Pawel J, Pujol JL, Papai Z, Quoix E, Ardizzoni A, Poulin R, Preston AJ, Dane G, Ross G. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol. 2007 May 20;25(15):2086-92. [ | + | # Eckardt JR, von Pawel J, Pujol JL, Papai Z, Quoix E, Ardizzoni A, Poulin R, Preston AJ, Dane G, Ross G. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol. 2007 May 20;25(15):2086-92. [https://doi.org/10.1200/jco.2006.08.3998 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17513814/ PubMed] |
<!-- Presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011, and 14th World Conference on Lung Cancer, Amsterdam, the Netherlands, July 3-7, 2011. --> | <!-- Presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011, and 14th World Conference on Lung Cancer, Amsterdam, the Netherlands, July 3-7, 2011. --> | ||
− | # von Pawel J, Jotte R, Spigel DR, O'Brien ME, Socinski MA, Mezger J, Steins M, Bosquée L, Bubis J, Nackaerts K, Trigo JM, Clingan P, Schütte W, Lorigan P, Reck M, Domine M, Shepherd FA, Li S, Renschler MF. Randomized | + | # '''ACT-1:''' von Pawel J, Jotte R, Spigel DR, O'Brien ME, Socinski MA, Mezger J, Steins M, Bosquée L, Bubis J, Nackaerts K, Trigo JM, Clingan P, Schütte W, Lorigan P, Reck M, Domine M, Shepherd FA, Li S, Renschler MF. Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. J Clin Oncol. 2014 Dec 10;32(35):4012-9. Epub 2014 Nov 10. [https://doi.org/10.1200/jco.2013.54.5392 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25385727/ PubMed] [https://clinicaltrials.gov/study/NCT00547651 NCT00547651] |
− | # Goto K, Ohe Y, Shibata T, Seto T, Takahashi T, Nakagawa K, Tanaka H, Takeda K, Nishio M, Mori K, Satouchi M, Hida T, Yoshimura N, Kozuki T, Imamura F, Kiura K, Okamoto H, Sawa T, Tamura T; | + | # '''JCOG0605:''' Goto K, Ohe Y, Shibata T, Seto T, Takahashi T, Nakagawa K, Tanaka H, Takeda K, Nishio M, Mori K, Satouchi M, Hida T, Yoshimura N, Kozuki T, Imamura F, Kiura K, Okamoto H, Sawa T, Tamura T; JCOG. Combined chemotherapy with cisplatin, etoposide, and irinotecan versus topotecan alone as second-line treatment for patients with sensitive relapsed small-cell lung cancer (JCOG0605): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1147-57. Epub 2016 Jun 14. [https://doi.org/10.1016/S1470-2045(16)30104-8 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27312053/ PubMed] UMIN000000828 |
+ | #'''GFPC 01-2013:''' Baize N, Monnet I, Greillier L, Geier M, Lena H, Janicot H, Vergnenegre A, Crequit J, Lamy R, Auliac JB, Letreut J, Le Caer H, Gervais R, Dansin E, Madroszyk A, Renault PA, Le Garff G, Falchero L, Berard H, Schott R, Saulnier P, Chouaid C; Groupe Français de Pneumo-Cancérologie. Carboplatin plus etoposide versus topotecan as second-line treatment for patients with sensitive relapsed small-cell lung cancer: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2020 Sep;21(9):1224-1233. [https://doi.org/10.1016/s1470-2045(20)30461-7 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32888454/ PubMed] [https://clinicaltrials.gov/study/NCT02738346 NCT02738346] | ||
+ | # '''CheckMate 331:''' Spigel DR, Vicente D, Ciuleanu TE, Gettinger S, Peters S, Horn L, Audigier-Valette C, Pardo Aranda N, Juan-Vidal O, Cheng Y, Zhang H, Shi M, Luft A, Wolf J, Antonia S, Nakagawa K, Fairchild J, Baudelet C, Pandya D, Doshi P, Chang H, Reck M. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331. Ann Oncol. 2021 May;32(5):631-641. Epub 2021 Feb 1. [https://doi.org/10.1016/j.annonc.2021.01.071 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33539946/ PubMed] [https://clinicaltrials.gov/study/NCT02481830 NCT02481830] | ||
+ | #'''TAHOE:''' Blackhall F, Jao K, Greillier L, Cho BC, Penkov K, Reguart N, Majem M, Nackaerts K, Syrigos K, Hansen K, Schuette W, Cetnar J, Cappuzzo F, Okamoto I, Erman M, Langer SW, Kato T, Groen H, Sun Z, Luo Y, Tanwani P, Caffrey L, Komarnitsky P, Reinmuth N. Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE Study. J Thorac Oncol. 2021 Sep;16(9):1547-1558. Epub 2021 Feb 16. [https://doi.org/10.1016/j.jtho.2021.02.009 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33607312/ PubMed] [https://clinicaltrials.gov/study/NCT03061812 NCT03061812] | ||
+ | #'''DISTINCT:''' Edelman MJ, Dvorkin M, Laktionov K, Navarro A, Juan-Vidal O, Kozlov V, Golden G, Jordan O, Deng CQ, Bentsion D, Chouaid C, Dechev H, Dowlati A, Fernández Núñez N, Ivashchuk O, Kiladze I, Kortua T, Leighl N, Luft A, Makharadze T, Min Y, Quantin X; DISTINCT study investigators. Randomized phase 3 study of the anti-disialoganglioside antibody dinutuximab and irinotecan vs irinotecan or topotecan for second-line treatment of small cell lung cancer. Lung Cancer. 2022 Apr;166:135-142. Epub 2022 Mar 4. [https://doi.org/10.1016/j.lungcan.2022.03.003 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35278766/ PubMed] [https://clinicaltrials.gov/study/NCT03098030 NCT03098030] | ||
+ | #'''ATLANTIS:''' Aix SP, Ciuleanu TE, Navarro A, Cousin S, Bonanno L, Smit EF, Chiappori A, Olmedo ME, Horvath I, Grohé C, Farago AF, López-Vilariño JA, Cullell-Young M, Nieto A, Vasco N, Gómez J, Kahatt C, Zeaiter A, Carcereny E, Roubec J, Syrigos K, Lo G, Barneto I, Pope A, Sánchez A, Kattan J, Zarogoulidis K, Waller CF, Bischoff H, Juan-Vidal O, Reinmuth N, Dómine M, Paz-Ares L. Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial. Lancet Respir Med. 2023 Jan;11(1):74-86. Epub 2022 Oct 14. [https://doi.org/10.1016/s2213-2600(22)00309-5 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/36252599/ PubMed] [https://clinicaltrials.gov/study/NCT02566993 NCT02566993] | ||
+ | #'''RESILIENT Part 2:''' Spigel DR, Dowlati A, Chen Y, Navarro A, Yang JC, Stojanovic G, Jove M, Rich P, Andric ZG, Wu YL, Rudin CM, Chen H, Zhang L, Yeung S, Benzaghou F, Paz-Ares L, Bunn PA; RESILIENT Trial Investigators. RESILIENT Part 2: A Randomized, Open-Label Phase III Study of Liposomal Irinotecan Versus Topotecan in Adults With Relapsed Small Cell Lung Cancer. J Clin Oncol. 2024 Jul 1;42(19):2317-2326. Epub 2024 Apr 22. [https://doi.org/10.1200/jco.23.02110 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/38648575/ PubMed] [https://clinicaltrials.gov/study/NCT03088813 NCT03088813] | ||
− | ==Vinorelbine | + | ==Vinorelbine monotherapy {{#subobject:4177e0|Regimen=1}}== |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, 25 mg/m<sup>2</sup> {{#subobject:be1346|Variant=1}}=== | ||
+ | {| class="wikitable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1159/000227555 Furuse et al. 1996a] | ||
+ | |Not reported in abstract | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
− | |||
|} | |} | ||
− | ===Regimen {{#subobject:f20f90|Variant=1}}=== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | {| | + | ====Chemotherapy==== |
− | | | + | *[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 |
− | |[[Levels_of_Evidence#Evidence| | + | '''21-day cycles''' |
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 30 mg/m<sup>2</sup> {{#subobject:f20f90|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/0959-8049(93)90112-s Jassem et al. 1993] |
− | |style="background-color:# | + | |1990-06 to 1991-05 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once | + | *[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV over 20 minutes once on day 1 |
+ | '''7-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Jassem J, Karnicka-Mlodkowska H, van Pottelsberghe C, van Glabbeke M, Noseda MA, Ardizzoni A, Gozzelino F, Planting A, van Zandwijk N. Phase II study of vinorelbine (Navelbine) in previously treated small cell lung cancer patients | + | # Jassem J, Karnicka-Mlodkowska H, van Pottelsberghe C, van Glabbeke M, Noseda MA, Ardizzoni A, Gozzelino F, Planting A, van Zandwijk N; [[Study_Groups#EORTC|EORTC]] Lung Cancer Cooperative Group. Phase II study of vinorelbine (Navelbine) in previously treated small cell lung cancer patients. Eur J Cancer. 1993;29A(12):1720-2. [https://doi.org/10.1016/0959-8049(93)90112-s link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8398301/ PubMed] |
− | + | # Furuse K, Kubota K, Kawahara M, Takada M, Kimura I, Fujii M, Ohta M, Hasegawa K, Yoshida K, Nakajima S, Ogura T, Niitani H; Japan Lung Cancer Vinorelbine Study Group. Phase II study of vinorelbine in heavily previously treated small cell lung cancer. Oncology. 1996 Mar-Apr;53(2):169-72. [https://doi.org/10.1159/000227555 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8604245/ PubMed] | |
− | [[Category: | + | [[Category:Small cell lung cancer regimens]] |
− | [[Category: | + | [[Category:Disease-specific pages]] |
− | [[Category: | + | [[Category:Lung cancers]] |
Latest revision as of 00:12, 25 July 2024
Section editor | |
---|---|
Amit Kulkarni, MBBS University of Minnesota Minneapolis, MN, USA |
Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!.
50 regimens on this page
102 variants on this page
|
Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
ASCO
- 2021: Daly et al. Radiation Therapy for Small-Cell Lung Cancer: ASCO Guideline Endorsement of an ASTRO Guideline PubMed
- 2020: Schneider et al. Lung Cancer Surveillance After Definitive Curative-Intent Therapy: ASCO Guideline PubMed
- 2015: Rudin et al. Treatment of small-cell lung cancer: American Society of Clinical Oncology endorsement of the American College of Chest Physicians guideline PubMed
ASCO-Ontario Health
- 2023: Khurshid et al. Systemic Therapy for Small-Cell Lung Cancer: ASCO-Ontario Health (Cancer Care Ontario) Guideline PubMed
ESMO
- 2021: Dingemans et al. Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up link to PMC article PubMed
- 2013: Früh et al. Small-cell lung cancer (SCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PubMed
- 2010: Sørensen et al. Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2009: Sørensen & Felip. Small-cell lung cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2005: Felip et al. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of small-cell lung cancer (SCLC) PubMed
- 2001: ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of small-cell lung cancer (SCLC) PubMed
NCCN
- NCCN Guidelines - Small Cell Lung Cancer
- 2021: Ganti et al. Small Cell Lung Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. link to PMC article PubMed
- 2013: Kalemkerian et al. Small cell lung cancer. link to PMC article PubMed
- 2011: Kalemkerian et al. Small cell lung cancer. PubMed
- 2006: Johnson et al. Small cell lung cancer clinical practice guidelines in oncology. PubMed
- 2004: Authors not listed. Small cell lung cancer. Clinical practice guidelines in oncology. PubMed
SITC
- 2022: Govindan et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lung cancer and mesothelioma link to PMC article PubMed
Limited stage, induction
Carboplatin & Etoposide (CE)
EP: Etoposide, Paraplatin (Carboplatin)
Regimen variant #1, 2 days of oral etoposide per cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lee et al. 2009 (LLCG-STUDY-12) | 2003-2006 | Phase 3 (C) | CE & Thalidomide, then RT | Did not meet primary endpoint of OS Median OS: 10.5 vs 10.1 mo (HR 0.92, 95% CI 0.79-1.08) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once on day 1, then 100 mg PO twice per day on days 2 & 3
21-day cycle for up to 6 cycles
Subsequent treatment
- LLCG-STUDY-12, patients with PR/CR: Definitive thoracic radiotherapy and prophylactic cranial irradiation, approximately 3 weeks after the last cycle, "according to local practice".
Regimen variant #2, 1 day of oral etoposide per cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lee et al. 2009 (LLCG-STUDY-12) | 2003-2006 | Phase 3 (C) | CE & Thalidomide, then RT | Did not meet primary endpoint of OS Median OS: 10.5 vs 10.1 mo (HR 0.92, 95% CI 0.79-1.08) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 & 2, then 100 mg PO twice per day on day 3
21-day cycle for up to 6 cycles
Subsequent treatment
- LLCG-STUDY-12, patients with PR/CR: Definitive thoracic radiotherapy and prophylactic cranial irradiation, approximately 3 weeks after the last cycle, "according to local practice".
References
- LLCG-STUDY-12: Lee SM, Woll PJ, Rudd R, Ferry D, O'Brien M, Middleton G, Spiro S, James L, Ali K, Jitlal M, Hackshaw A. Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2009 Aug 5;101(15):1049-57. Epub 2009 Jul 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00061919
Cisplatin & Etoposide (EP)
EP: Etoposide, Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Evans et al. 1985 | 1981-1984 | Phase 2 |
Note: Patients with limited stage disease responding to therapy received prophylactic cranial irradiation, 400 cGy fractions once per day x 5 fractions (total dose: 2000 cGy) over 5 days between cycles 3 and 4.
Chemotherapy
- Cisplatin (Platinol) 25 mg/m2 IV slow push once per day on days 1 to 3, given second
- Etoposide (Vepesid) 100 mg/m2 IV over at least 30 minutes once per day on days 1 to 3, given first
Supportive therapy
- Dexamethasone (Decadron) 10 mg IV once per day on days 1 to 3, prior to chemotherapy
- Metoclopramide (Reglan) 10 mg IV or PO once per day on days 1 to 3, prior to chemotherapy
- Prochlorperazine (Compazine) 10 mg IM or PO once per day on days 1 to 3, prior to chemotherapy
- "No special efforts were made to hydrate the patients," though PO fluid intake was encouraged, and 500 mL normal saline was given with etoposide infusion.
21- to 28-day cycle for 6 cycles
Subsequent treatment
- Definitive thoracic radiation
References
- Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Limited stage, definitive chemoradiotherapy
Carboplatin, Etoposide, RT
EP & RT: Etoposide, Paraplatin (Carboplatin), Radiation Therapy
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Skarlos et al. 2001 | 1993-1999 | Randomized Phase 2 (E-switch-ic) | Carboplatin, Etoposide, RT; early HTRT | Might have superior ORR (primary endpoint) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 60 minutes once on day 1, given first, before etoposide
- Etoposide (Vepesid) 100 mg/m2 IV over 2 hours once per day on days 1 to 3, given second, after carboplatin
Radiotherapy
- Concurrent hyperfractionated thoracic radiation therapy (HTRT), 150 cGy fractions given twice per day (at least 4, but preferably 6 hours between fractions) x 30 fractions (total dose: 4500 cGy) over 3 weeks. Skarlos et al. 2001 examined two different timings for radiation therapy. There was no significant difference between early vs. late HTRT, though there was a trend toward higher response rate for late HTRT. Early HTRT is given during cycle 1 of chemotherapy; late HTRT is given during cycle 4 of chemotherapy.
21-day cycle for up to 6 cycles
Subsequent treatment
- Skarlos et al. 2001, patients with CR: Prophylactic cranial irradiation
Regimen variant #2
Study | Dates of enrollment | Evidence |
---|---|---|
Okamoto et al. 1999 | 1995-1996 | Phase 2 |
Eligibility criteria
- At least 70 years old
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1, given first
- Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes once per day on days 1 to 3, given second
Radiotherapy
- Thoracic radiation, given third
- Palliative radiation therapy was allowed to control persistent pain from bony metastases
Supportive therapy
- Dexamethasone (Decadron) 8 mg IV once per day on days 1 to 3, prior to chemotherapy
- Granisetron 40 mcg/kg IV once per day on days 1 to 3, prior to chemotherapy
- G-CSF (type not specified) 2 mcg/kg SC given for grade 3 or greater leukopenia/neutropenia
28-day cycle for up to 4 cycles
References
- Okamoto H, Watanabe K, Nishiwaki Y, Mori K, Kurita Y, Hayashi I, Masutani M, Nakata K, Tsuchiya S, Isobe H, Saijo N. Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer. J Clin Oncol. 1999 Nov;17(11):3540-5. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Skarlos DV, Samantas E, Briassoulis E, Panoussaki E, Pavlidis N, Kalofonos HP, Kardamakis D, Tsiakopoulos E, Kosmidis P, Tsavdaridis D, Tzitzikas J, Tsekeris P, Kouvatseas G, Zamboglou N, Fountzilas G; Hellenic Cooperative Oncology Group. Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol. 2001 Sep;12(9):1231-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Cisplatin, Etoposide, RT
EP & RT: Etoposide, Platinol (Cisplatin), Radiation Therapy
PE + RT: Platinol (Cisplatin), Etoposide, Radiation Therapy
Regimen variant #1, 60/360/45
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Turrisi et al. 1999 (Intergroup 0096) | 1989-1992 | Phase 3 (E-esc) | EP & RT; once per day RT | Seems to have superior OS |
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 to 3
Radiotherapy
- Concurrent radiation therapy, 150 cGy fractions given twice per day x 30 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 4500 cGy)
21-day cycle for 4 cycles
Subsequent treatment
- After completing 4 cycles of chemotherapy, patients were restaged. Because of the high rate of brain metastases (50%), patients with CR were offered prophylactice cranial irradiation
Regimen variant #2, 70/300/52.5, early RT
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Sun et al. 2013 (SMC 2003-02-016) | 2003-2010 | Phase 3 (C) | EP & RT; late RT | Non-inferior CR rate | Seems to have higher rates of neutropenic fever |
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
Radiotherapy
- Concurrent radiation therapy, 210 cGy fractions x 25 fractions over 5 weeks, given during cycle 1 of chemotherapy (total dose: 5250 cGy)
21-day cycle for 4 cycles
Regimen variant #3, 70/300/52.5, late RT
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Sun et al. 2013 (SMC 2003-02-016) | 2003-2010 | Phase 3 (E-switch-ic) | EP & RT; early RT | Non-inferior CR rate (primary endpoint) | Seems to have lower rates of neutropenic fever |
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
Radiotherapy
- Concurrent radiation therapy, 210 cGy fractions x 25 fractions over 5 weeks, given during cycle 3 of chemotherapy (total dose: 5250 cGy)
21-day cycle for 4 cycles
Regimen variant #4, 75/180/45, pre-planned dose reduction
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Bunn et al. 1995 | 1989-1991 | Phase 3 (C) | EP & RT; with GM-CSF support | Did not meet secondary endpoints | Less toxic |
Note: toxicity was the primary endpoint in this study.
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 to 3: 25 mg/m2 IV once per day on days 1 to 3
- Cycles 4 to 6: 40 mg/m2 IV once on day 1
- Etoposide (Vepesid) as follows:
- Cycles 1 to 3: 60 mg/m2 IV once per day on days 1 to 3
- Cycles 4 to 6: 50 mg/m2 IV once per day on days 1 to 3
Radiotherapy
- Concurrent radiation therapy during cycles 1 & 2, 180 cGy fractions x 25 fractions (total dose: 4500 cGy)
21-day cycle for 6 cycles
Regimen variant #5, 75/300/45
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Faivre-Finn et al. 2017 (CONVERT) | 2008-2013 | Phase 3 (E-esc) | EP & RT; once per day RT | Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
Radiotherapy
- Concurrent radiation therapy, 150 cGy fractions given twice per day x 30 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 4500 cGy)
21-day cycle for 4 or 6 cycles
Regimen variant #6, 75/300/45, split doses of cisplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Faivre-Finn et al. 2017 (CONVERT) | 2008-2013 | Phase 3 (E-esc) | EP & RT; once per day RT | Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 25 mg/m2 IV once per day on days 1 to 3
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
Radiotherapy
- Concurrent radiation therapy, 150 cGy fractions given twice per day x 30 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 4500 cGy)
21-day cycle for 4 or 6 cycles
Regimen variant #7, 75/700/42, partially oral etoposide
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sundstrøm et al. 2002 | 1989-1994 | Phase 3 (E-switch-ic) | CEV & RT | Superior OS |
Note: Oral etoposide to be taken on an empty stomach.
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once on day 1, then 200 mg/m2 PO once per day on days 2 to 4
Radiotherapy
- Concurrent thoracic radiation therapy, 280 cGy fractions once per day x 15 fractions (total dose: 4200 cGy) over 3 weeks, given "between the third and fourth chemotherapy courses"
Supportive therapy
- "Standard prehydration and posthydration procedures were followed in conjunction with cisplatin administration."
21-day cycle for up to 5 cycles
Subsequent treatment
- Sundstrøm et al. 2002, patients with CR: Prophylactic cranial irradiation
Regimen variant #8, 80/240/50
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
McClay et al. 2005 (CALGB 9235) | 1993-1999 | Phase 3 (E-de-esc) | EP, Tamoxifen, RT | Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Etoposide (Vepesid) 80 mg/m2 IV once per day on days 1 to 3
Radiotherapy
- Concurrent thoracic radiation therapy, 200 cGy fractions once per day x 25 fractions (total dose: 5000 cGy) over 5 weeks, started on cycle 4 day 1 of chemotherapy
21-day cycle for 5 cycles
Regimen variant #9, 80/300/45, 1 cycle of chemo
Study | Dates of enrollment | Evidence |
---|---|---|
Saito et al. 2006 (WJTOG 9902) | 2000-2002 | Phase 2 |
Kubota et al. 2013 (JCOG0202) | 2002-2006 | Non-randomized part of phase 3 RCT |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
Radiotherapy
- Concurrent thoracic radiation therapy, 150 cGy fractions given twice per day (at least 4, but preferably 6 hours between fractions) x 30 fractions (total dose: 4500 cGy) over 3 weeks, started on cycle 1 day 2 of chemotherapy
28-day course
Regimen variant #10, 80/300/45, 4 cycles of chemo
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Takada et al. 2002 (JCOG 9104) | 1991-1995 | Phase 3 (E-switch-ic) | EP, then RT | Might have superior OS |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
Radiotherapy
- Concurrent thoracic radiation therapy, 150 cGy fractions given twice per day (4 or more hours between fractions) x 30 fractions (total dose: 4500 cGy) over 3 weeks, started on cycle 1 day 2 of chemotherapy
28-day cycle for 4 cycles
Subsequent treatment
- JCOG 9104, patients with CR or near-CR ("a scar-like shadow on chest films but no positive cytology and/or bronchoscopic biopsy"): Prophylactic cranial irradiation
Regimen variant #11, 90/300/39.9
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sculier et al. 2008 | 1993-2006 | Phase 3 (E-switch-ic) | EP & RT; daily cisplatin | Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 90 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
Radiotherapy
- Concurrent radiation therapy, 266 cGy fractions once per day x 15 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 3990 cGy)
21-day cycle for up to 6 cycles
References
- Bunn PA Jr, Crowley J, Kelly K, Hazuka MB, Beasley K, Upchurch C, Livingston R; SWOG. Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group. J Clin Oncol. 1995 Jul;13(7):1632-41. Erratum in: J Clin Oncol 1995 Nov;13(11):2860. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Intergroup 0096: Turrisi AT 3rd, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, Wagner H, Aisner S, Johnson DH. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999 Jan 28;340(4):265-71. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- JCOG 9104: Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, Nishiwaki Y, Watanabe K, Noda K, Tamura T, Fukuda H, Saijo N. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol. 2002 Jul 15;20(14):3054-60. link to original article dosing details in manuscript have been reviewed by our editors PubMed content property of HemOnc.org
- Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Schild SE, Bonner JA, Shanahan TG, Brooks BJ, Marks RS, Geyer SM, Hillman SL, Farr GH Jr, Tazelaar HD, Krook JE, Geoffroy FJ, Salim M, Arusell RM, Mailliard JA, Schaefer PL, Jett JR. Long-term results of a phase III trial comparing once-daily radiotherapy with twice-daily radiotherapy in limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2004 Jul 15;59(4):943-51. link to original article PubMed
- CALGB 9235: McClay EF, Bogart J, Herndon JE 2nd, Watson D, Evans L, Seagren SL, Green MR; CALGB. A phase III trial evaluating the combination of cisplatin, etoposide, and radiation therapy with or without tamoxifen in patients with limited-stage small cell lung cancer: Cancer and Leukemia Group B Study (9235). Am J Clin Oncol. 2005 Feb;28(1):81-90. link to original article dosing details in abstract have been reviewed by our editors PubMed
- WJTOG 9902: Saito H, Takada Y, Ichinose Y, Eguchi K, Kudoh S, Matsui K, Nakagawa K, Takada M, Negoro S, Tamura K, Ando M, Tada T, Fukuoka M; West Japan Thoracic Oncology Group. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902. J Clin Oncol. 2006 Nov 20;24(33):5247-52. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Sculier JP, Lafitte JJ, Efremidis A, Florin MC, Lecomte J, Berchier MC, Richez M, Berghmans T, Scherpereel A, Meert AP, Koumakis G, Leclercq N, Paesmans M, Van Houtte P; European Lung Cancer Working Party. A phase III randomised study of concomitant induction radiochemotherapy testing two modalities of radiosensitisation by cisplatin (standard versus daily) for limited small-cell lung cancer. Ann Oncol. 2008 Oct;19(10):1691-7. Epub 2008 May 25. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- SMC 2003-02-016: Sun JM, Ahn YC, Choi EK, Ahn MJ, Ahn JS, Lee SH, Lee DH, Pyo H, Song SY, Jung SH, Jo JS, Jo J, Sohn HJ, Suh C, Lee JS, Kim SW, Park K. Phase III trial of concurrent thoracic radiotherapy with either first- or third-cycle chemotherapy for limited-disease small-cell lung cancer. Ann Oncol. 2013 Aug;24(8):2088-92. Epub 2013 Apr 16. Erratum in: Ann Oncol. 2014 Aug;25(8):1672. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01125995
- JCOG0202: Kubota K, Hida T, Ishikura S, Mizusawa J, Nishio M, Kawahara M, Yokoyama A, Imamura F, Takeda K, Negoro S, Harada M, Okamoto H, Yamamoto N, Shinkai T, Sakai H, Matsui K, Nakagawa K, Shibata T, Saijo N, Tamura T; JCOG. Etoposide and cisplatin versus irinotecan and cisplatin in patients with limited-stage small-cell lung cancer treated with etoposide and cisplatin plus concurrent accelerated hyperfractionated thoracic radiotherapy (JCOG0202): a randomised phase 3 study. Lancet Oncol. 2014 Jan;15(1):106-13. Epub 2013 Dec 3. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00144989
- CONVERT: Faivre-Finn C, Snee M, Ashcroft L, Appel W, Barlesi F, Bhatnagar A, Bezjak A, Cardenal F, Fournel P, Harden S, Le Pechoux C, McMenemin R, Mohammed N, O'Brien M, Pantarotto J, Surmont V, Van Meerbeeck JP, Woll PJ, Lorigan P, Blackhall F; CONVERT Study Team. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol. 2017 Aug;18(8):1116-1125. Epub 2017 Jun 20. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00433563
- CALGB 30610: NCT00632853
Limited stage, adjuvant therapy
Cisplatin & Etoposide (EP)
EP: Etoposide & Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kenmotsu et al. 2020 (JCOG1205/1206) | 2013-2018 | Phase 3 (C) | Cisplatin & Irinotecan | Did not meet primary endpoint of RFS RFS36: 65.4% vs 69% (HR 0.93, 95% CI 0.58-1.50) |
Preceding treatment
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
21-day cycle for up to 4 cycles
References
- JCOG1205/1206: Kenmotsu H, Niho S, Tsuboi M, Wakabayashi M, Ishii G, Nakagawa K, Daga H, Tanaka H, Saito H, Aokage K, Takahashi T, Menju T, Kasai T, Yoshino I, Minato K, Okada M, Eba J, Asamura H, Ohe Y, Watanabe SI. Randomized Phase III Study of Irinotecan Plus Cisplatin Versus Etoposide Plus Cisplatin for Completely Resected High-Grade Neuroendocrine Carcinoma of the Lung: JCOG1205/1206. J Clin Oncol. 2020 Dec 20;38(36):4292-4301. Epub 2020 Nov 2. link to original article dosing details in manuscript have been reviewed by our editors PubMed UMIN000010298
Limited stage, consolidation after upfront therapy
Cisplatin & Irinotecan (IC)
IP: Irinotecan, Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Saito et al. 2006 (WJTOG 9902) | 2000-2002 | Phase 2 |
Preceding treatment
- Definitive Cisplatin, Etoposide, RT
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Irinotecan (Camptosar) 60 mg/m2 IV once per day on days 1, 8, 15
Supportive therapy
- G-CSF (no additional details given) starting after day 4
28-day cycle for 3 cycles
Subsequent treatment
- WJTOG 9902, patients with CR or good PR: Prophylactic cranial irradiation
References
- WJTOG 9902: Saito H, Takada Y, Ichinose Y, Eguchi K, Kudoh S, Matsui K, Nakagawa K, Takada M, Negoro S, Tamura K, Ando M, Tada T, Fukuoka M; West Japan Thoracic Oncology Group. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902. J Clin Oncol. 2006 Nov 20;24(33):5247-52. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Radiation therapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Evans et al. 1985 | 1981-1984 | Phase 2 |
Preceding treatment
- Induction EP x 6
Radiotherapy
- "Patients who did not have evidence of tumor spread beyond the mediastinum and/or ipsilateral supraclavicular notes" received thoracic radiation in 250 cGy fractions x 10 fractions (total dose: 2500 cGy)
References
- Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- LLCG-STUDY-12: Lee SM, Woll PJ, Rudd R, Ferry D, O'Brien M, Middleton G, Spiro S, James L, Ali K, Jitlal M, Hackshaw A. Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2009 Aug 5;101(15):1049-57. Epub 2009 Jul 16. link to original article does not contain dosing details PubMed NCT00061919
Whole brain irradiation
PCI: Prophylactic Cranial Irradiation
Regimen variant #1, 2000 cGy
Study | Dates of enrollment | Evidence |
---|---|---|
Cox et al. 1981 | 1975-1978 | Non-randomized |
Evans et al. 1985 | 1981-1984 | Phase 2 |
Skarlos et al. 2001 | 1993-1999 | Non-randomized part of phase 2 RCT |
Note: in Evans et al. 1985, the WB-XRT is given in-between cycles 3 & 4.
Preceding treatment
- Evans et al. 1985: Induction EP x 3
- Skarlos et al. 2001: Definitive EP & early HTRT versus EP & late HTRT
Radiotherapy
- Whole brain irradiation, 400 cGy fractions once per day x 5 fractions (total dose: 2000 cGy)
1-week course
Subsequent treatment
- Evans et al. 1985: EP consolidation x 3
Regimen variant #2, 2400 cGy
Study | Dates of enrollment | Evidence |
---|---|---|
Takada et al. 2002 (JCOG 9104) | 1991-1995 | Non-randomized part of phase 3 RCT |
Radiotherapy
- Whole brain irradiation, 150 cGy fractions given twice per day x 16 fractions (total dose: 2400 cGy)
2-week course
Regimen variant #3, 2500 cGy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Turrisi et al. 1999 (Intergroup 0096) | 1989-1992 | Non-randomized part of phase 3 RCT | ||
Le Péchoux et al. 2009 (PCI 99-01/EORTC 22003-08004/RTOG 0212/IFCT 99-01) | 1999-2005 | Phase 3 (C) | PCI x 36 Gy | Did not meet primary endpoint of incidence of brain metastases at 2 years |
Saito et al. 2006 (WJTOG 9902) | 2000-2002 | Phase 2 |
Preceding treatment
- Intergroup 0096: Definitive EP & once-daily RT versus EP & twice-daily RT
- WJTOG 9902: Definitive EP & RT, then IP consolidation x 3
Radiotherapy
- Whole brain irradiation, 250 cGy fractions x 10 fractions (total dose: 2500 cGy)
2-week course
Regimen variant #4, 3000 cGy
Study | Dates of enrollment | Evidence |
---|---|---|
Sundstrøm et al. 2002 | 1989-1994 | Non-randomized part of phase 3 RCT |
Radiotherapy
- Whole brain irradiation, 200 cGy fractions once per day x 15 fractions (total dose: 3000 cGy)
3-week course
References
- Cox JD, Stanley K, Petrovich Z, Paig C, Yesner R. Cranial irradiation in cancer of the lung of all cell types. JAMA. 1981 Feb 6;245(5):469-72. link to original article PubMed
- Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Intergroup 0096: Turrisi AT 3rd, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, Wagner H, Aisner S, Johnson DH. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999 Jan 28;340(4):265-71. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Meta-analysis: Aupérin A, Arriagada R, Pignon JP, Le Péchoux C, Gregor A, Stephens RJ, Kristjansen PE, Johnson BE, Ueoka H, Wagner H, Aisner J; Prophylactic Cranial Irradiation Overview Collaborative Group. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med. 1999 Aug 12;341(7):476-84. link to original article PubMed
- JCOG 9104: Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, Nishiwaki Y, Watanabe K, Noda K, Tamura T, Fukuda H, Saijo N. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol. 2002 Jul 15;20(14):3054-60. link to original article dosing details in manuscript have been reviewed by our editors PubMed content property of HemOnc.org
- Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- WJTOG 9902: Saito H, Takada Y, Ichinose Y, Eguchi K, Kudoh S, Matsui K, Nakagawa K, Takada M, Negoro S, Tamura K, Ando M, Tada T, Fukuoka M; West Japan Thoracic Oncology Group. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902. J Clin Oncol. 2006 Nov 20;24(33):5247-52. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- PCI 99-01/EORTC 22003-08004/RTOG 0212/IFCT 99-01: Le Péchoux C, Dunant A, Senan S, Wolfson A, Quoix E, Faivre-Finn C, Ciuleanu T, Arriagada R, Jones R, Wanders R, Lerouge D, Laplanche A; Prophylactic Cranial Irradiation (PCI) Collaborative Group. Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212, and IFCT 99-01): a randomised clinical trial. Lancet Oncol. 2009 May;10(5):467-74. Epub 2009 Apr 20. link to original article PubMed NCT00005062
Extensive stage, induction
Belotecan & Cisplatin
BP: Belotecan and Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Oh et al. 2016 (COMBAT) | 2009-2013 | Phase 3 (E-switch-ic) | EP; 60/100 | Non-inferior RR (primary endpoint) |
Note: the total number of planned cycles is not described in the manuscript; total duration information here was provided by the authors.
Chemotherapy
- Belotecan (Camptobell) 0.5 mg/m2 IV over 30 minutes once per day on days 1 to 4
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
21-day cycle for 4 to 8 cycles
References
- COMBAT: Oh IJ, Kim KS, Park CK, Kim YC, Lee KH, Jeong JH, Kim SY, Lee JE, Shin KC, Jang TW, Lee HK, Lee KY, Lee SY. Belotecan/cisplatin versus etoposide/cisplatin in previously untreated patients with extensive-stage small cell lung carcinoma: a multi-center randomized phase III trial. BMC Cancer. 2016 Aug 26;16:690. link to original article link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00826644
Carboplatin & Etoposide (CE)
CE: Carboplatin & Etoposide
EP: Etoposide & Paraplatin (Carboplatin)
EC: Etoposide & Carboplatin
Ca/E: Carboplatin & Etoposide
Regimen variant #1, AUC 4/600, PO etoposide
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hermes et al. 2008 | 2001-2005 | Phase 3 (C) | Carboplatin & Irinotecan | Inferior OS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 4 (Chatelut formula) IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 PO once per day on days 1 to 5
21-day cycle for 4 cycles
Regimen variant #2, AUC 5/240
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Okamoto et al. 2007 (JCOG 9702) | 1998-2004 | Phase 3 (E-switch-ic) | EP; split-dose | Did not meet primary endpoint of OS |
Sekine et al. 2013 (D0702002) | 2006-07-04 to 2007-09-05 | Phase 3 (C) | Amrubicin | Inconclusive whether non-inferior OS (primary endpoint) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Etoposide (Vepesid) 80 mg/m2 IV once per day on days 1 to 3
Supportive therapy
- JCOG 9702: G-CSF
21-day cycle for varying durations: 4 cycles (JCOG 9702); 4 to 6 cycles (D0702002)
Regimen variant #3, AUC 5/300, 21-day cycles
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Socinski et al. 2009 (JMHO) | 2006-08 to 2007-12 | Phase 3 (C) | Carboplatin & Pemetrexed | Superior OS1 (primary endpoint) Median OS: 10.6 vs 8.1 mo (HR 0.64, 95% CI 0.52-0.79) |
Spigel et al. 2011 (SALUTE) | 2007-2008 | Randomized Phase 2 (C) | 1a. CE & Bevacizumab 1b. EP & Bevacizumab |
Seems to have inferior PFS |
Ready et al. 2015 (CALGB 30504) | 2007-2011 | Non-randomized part of phase 2 RCT | ||
Reck et al. 2016 (CA184-156) | 2012-2014 | Phase 3 (C) | 1a. CE & Ipilimumab 1b. EP & Ipilimumab |
Did not meet primary endpoint of OS Median OS: 10.9 vs 11 mo (HR 1.06, 95% CI 0.92-1.23) |
Jalal et al. 2017 (MATISSE) | 2012-2013 | Randomized Phase 2 (C) | PaCE | Might have superior OS Median OS: 10.37 vs 10.03 mo (HR 0.77, 95% CI 0.56-1.05) |
Horn et al. 2018 (IMpower133) | 2016-06-06 to 2017-05-31 | Phase 3 (C) | CE & Atezolizumab | Seems to have inferior OS2 |
Paz-Ares et al. 2019 (CASPIAN) | 2017-03-27 to 2018-05-29 | Phase 3 (C) | 1a. CE & Durvalumab 1b. EP & Durvalumab |
Inferior OS |
Rudin et al. 2020 (KEYNOTE-604) | 2017-05-15 to 2018-07-30 | Phase 3 (C) | 1a. CE & Pembrolizumab 1b. EP & Pembrolizumab |
Seems to have inferior OS |
Wang et al. 2022 (CAPSTONE-1) | 2018-2020 | Phase 3 (C) | CE & Adebrelimab | Inferior OS |
Cheng et al. 2024 (RATIONALE-312) | 2019-07-22 to 2021-04-21 | Phase 3 (C) | 1a. CE & Tislelizumab 1b. EP & Tislelizumab |
Inferior OS |
1JMHO was designed as a non-inferiority trial; however, the control arm was found to be statistically superior for the primary endpoint of OS.
2Reported efficacy for IMpower133 is based on the 2020 update.
Note: CASPIAN gave a range of dosing; see paper for details.
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
Supportive therapy
- Socinksi et al. 2009: "supportive therapies, such as erythropoietic agents or granulocyte colony-stimulating factors, were administered according to the American Society of Clinical Oncology guidelines"
21-day cycle for varying durations: 4 cycles (CASPIAN, RATIONALE-312); 4 to 6 cycles
Subsequent treatment
- CALGB 30504, SD or better: Observation versus sunitinib maintenance
Regimen variant #4, AUC 5/300, 28-day cycles
Study | Dates of enrollment | Evidence |
---|---|---|
Okamoto et al. 1999 | 1995-1996 | Phase 2 |
Quoix et al. 2001 | 1997-1999 | Phase 2 |
Eligibility criteria
- At least 70 years old
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1, given first
- Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes once per day on days 1 to 3, given second
Supportive therapy
- Dexamethasone (Decadron) 8 mg IV once per day on days 1 to 3, prior to chemotherapy
- Granisetron 40 mcg/kg IV once per day on days 1 to 3, prior to chemotherapy
- Okamoto et al. 1999: G-CSF (type not specified) 2 mcg/kg SC given for grade 3 or greater leukopenia/neutropenia
- Quiox et al. 2001: "Haematopoietic growth factors were allowed as prophylactic or curative treatment only if grade 4 neutropenia greater than 7 days occurred"
28-day cycle for varying durations: 4 cycles (Okamoto et al. 1999); 6 cycles (Quoix et al. 2001)
Subsequent treatment
- Palliative radiation therapy was allowed to control persistent pain from bony metastases
Regimen variant #5, AUC 5/360
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Seckl et al. 2017 (LUNGSTAR) | 2007-2012 | Phase 3 (C) | 1a. CE & Pravastatin 1b. EP & Pravastatin |
Did not meet primary endpoint of OS OS24: 14.1% vs 13.2% (HR 0.99, 95% CI 0.86-1.14) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 to 3
21-day cycle for 6 cycles
Regimen variant #6, AUC 5/420
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Heigener et al. 2009 | 2000-2003 | Phase 3 (C) | CE; dose-intense | Did not meet primary endpoint of OS |
Schmittel et al. 2006 | 2002-2008 | Randomized Phase 2 (E-switch-ic) | IP | Might have inferior OS (secondary endpoint) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1
- Etoposide (Vepesid) 140 mg/m2 IV over 90 minutes once per day on days 1 to 3
Supportive therapy
- 5-HT3 antagonist IV once per day on days 1 to 3, prior to chemotherapy
- Loperamide (Imodium) 4 mg PO prn first episode of diarrhea, then 2 mg PO Q2H until diarrhea stops
21- to 28-day cycle for up to 6 cycles
Regimen variant #7, AUC 5/440, 1 day of oral etoposide per cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lee et al. 2009 (LLCG-STUDY-12) | 2003-2006 | Phase 3 (C) | CE & Thalidomide | Did not meet primary endpoint of OS Median OS: 10.5 vs 10.1 mo (HR 0.92, 95% CI 0.79-1.08) |
Seckl et al. 2017 (LUNGSTAR) | 2007-2012 | Phase 3 (C) | 1a. CE & Pravastatin 1b. EP & Pravastatin |
Did not meet primary endpoint of OS OS24: 14.1% vs 13.2% (HR 0.99, 95% CI 0.86-1.14) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 & 2, then 100 mg PO twice per day on day 3
21-day cycle for up to 6 cycles
Regimen variant #8, AUC 5/520, 2 days of oral etoposide per cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lee et al. 2009 (LLCG-STUDY-12) | 2003-2006 | Phase 3 (C) | CE & Thalidomide | Did not meet primary endpoint of OS Median OS: 10.5 vs 10.1 mo (HR 0.92, 95% CI 0.79-1.08) |
Seckl et al. 2017 (LUNGSTAR) | 2007-2012 | Phase 3 (C) | 1a. CE & Pravastatin 1b. EP & Pravastatin |
Did not meet primary endpoint of OS OS24: 14.1% vs 13.2% (HR 0.99, 95% CI 0.86-1.14) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once on day 1, then 100 mg PO twice per day on days 2 & 3
21-day cycle for up to 6 cycles
Regimen variant #9, AUC 6/360
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Seckl et al. 2017 (LUNGSTAR) | 2007-2012 | Phase 3 (C) | 1a. CE & Pravastatin 1b. EP & Pravastatin |
Did not meet primary endpoint of OS OS24: 14.1% vs 13.2% (HR 0.99, 95% CI 0.86-1.14) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 to 3
21-day cycle for 6 cycles
Regimen variant #10, AUC 6/440, 1 day of oral etoposide per cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Seckl et al. 2017 (LUNGSTAR) | 2007-2012 | Phase 3 (C) | 1a. CE & Pravastatin 1b. EP & Pravastatin |
Did not meet primary endpoint of OS OS24: 14.1% vs 13.2% (HR 0.99, 95% CI 0.86-1.14) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 & 2, then 100 mg PO twice per day on day 3
21-day cycle for up to 6 cycles
Regimen variant #11, AUC 6/520, 2 days of oral etoposide per cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Seckl et al. 2017 (LUNGSTAR) | 2007-2012 | Phase 3 (C) | 1a. CE & Pravastatin 1b. EP & Pravastatin |
Did not meet primary endpoint of OS OS24: 14.1% vs 13.2% (HR 0.99, 95% CI 0.86-1.14) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once on day 1, then 100 mg PO twice per day on days 2 & 3
21-day cycle for up to 6 cycles
References
- Okamoto H, Watanabe K, Nishiwaki Y, Mori K, Kurita Y, Hayashi I, Masutani M, Nakata K, Tsuchiya S, Isobe H, Saijo N. Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer. J Clin Oncol. 1999 Nov;17(11):3540-5. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Quoix E, Breton JL, Daniel C, Jacoulet P, Debieuvre D, Paillot N, Kessler R, Moreau L, Coëtmeur D, Lemarié E, Milleron B. Etoposide phosphate with carboplatin in the treatment of elderly patients with small-cell lung cancer: a phase II study. Ann Oncol. 2001 Jul;12(7):957-62. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Schmittel A, Fischer von Weikersthal L, Sebastian M, Martus P, Schulze K, Hortig P, Reeb M, Thiel E, Keilholz U. A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer. Ann Oncol. 2006 Apr;17(4):663-7. Epub 2006 Jan 19. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Schmittel A, Sebastian M, Fischer von Weikersthal L, Martus P, Gauler TC, Kaufmann C, Hortig P, Fischer JR, Link H, Binder D, Fischer B, Caca K, Eberhardt WE, Keilholz U; Arbeitsgemeinschaft Internistische Onkologie Thoracic Oncology Study Group. A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol. 2011 Aug;22(8):1798-804. Epub 2011 Jan 25. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- JCOG 9702: Okamoto H, Watanabe K, Kunikane H, Yokoyama A, Kudoh S, Asakawa T, Shibata T, Kunitoh H, Tamura T, Saijo N. Randomised phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702. Br J Cancer. 2007 Jul 16;97(2):162-9. Epub 2007 Jun 19. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
- Hermes A, Bergman B, Bremnes R, Ek L, Fluge S, Sederholm C, Sundstrøm S, Thaning L, Vilsvik J, Aasebø U, Sörenson S. Irinotecan plus carboplatin versus oral etoposide plus carboplatin in extensive small-cell lung cancer: a randomized phase III trial. J Clin Oncol. 2008 Sep 10;26(26):4261-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Heigener DF, Manegold C, Jäger E, Saal JG, Zuna I, Gatzemeier U. Multicenter randomized open-label phase III study comparing efficacy, safety, and tolerability of conventional carboplatin plus etoposide versus dose-intensified carboplatin plus etoposide plus lenograstim in small-cell lung cancer in "extensive disease" stage. Am J Clin Oncol. 2009 Feb;32(1):61-4. link to original article dosing details in abstract have been reviewed by our editors PubMed
- LLCG-STUDY-12: Lee SM, Woll PJ, Rudd R, Ferry D, O'Brien M, Middleton G, Spiro S, James L, Ali K, Jitlal M, Hackshaw A. Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2009 Aug 5;101(15):1049-57. Epub 2009 Jul 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00061919
- JMHO: Socinski MA, Smit EF, Lorigan P, Konduri K, Reck M, Szczesna A, Blakely J, Serwatowski P, Karaseva NA, Ciuleanu T, Jassem J, Dediu M, Hong S, Visseren-Grul C, Hanauske AR, Obasaju CK, Guba SC, Thatcher N. Phase III study of pemetrexed plus carboplatin compared with etoposide plus carboplatin in chemotherapy-naive patients with extensive-stage small-cell lung cancer. J Clin Oncol. 2009 Oct 1;27(28):4787-92. Epub 2009 Aug 31. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00363415
- SALUTE: Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00403403
- D0702002: Sekine I, Okamoto H, Horai T, Nakagawa K, Ohmatsu H, Yokoyama A, Katakami N, Shibuya M, Saijo N, Fukuoka M. A randomized phase III study of single-agent amrubicin vs carboplatin/etoposide in elderly patients with extensive-disease small-cell lung cancer. Clin Lung Cancer. 2014 Mar;15(2):96-102. Epub 2013 Nov 14. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00286169
- CALGB 30504: Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, Baggstrom M, Masters GA, Graziano SL, Crawford J, Bogart J, Vokes EE. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: A randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (Alliance). J Clin Oncol. 2015 May 20;33(15):1660-5. Epub 2015 Mar 2. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00453154
- CA184-156: Reck M, Luft A, Szczesna A, Havel L, Kim SW, Akerley W, Pietanza MC, Wu YL, Zielinski C, Thomas M, Felip E, Gold K, Horn L, Aerts J, Nakagawa K, Lorigan P, Pieters A, Kong Sanchez T, Fairchild J, Spigel D. Phase III randomized trial of ipilimumab plus etoposide and platinum versus placebo plus etoposide and platinum in extensive-stage small-cell lung cancer. J Clin Oncol. 2016 Nov 1;34(31):3740-3748. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01450761
- LUNGSTAR: Seckl MJ, Ottensmeier CH, Cullen M, Schmid P, Ngai Y, Muthukumar D, Thompson J, Harden S, Middleton G, Fife KM, Crosse B, Taylor P, Nash S, Hackshaw A. Multicenter, phase III, randomized, double-blind, placebo-controlled trial of pravastatin added to first-line standard chemotherapy in small-cell lung cancer (LUNGSTAR). J Clin Oncol. 2017 May 10;35(14):1506-1514. Epub 2017 Feb 27. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00433498
- MATISSE: Jalal SI, Lavin P, Lo G, Lebel F, Einhorn L. Carboplatin and etoposide with or without palifosfamide in untreated extensive-stage small-cell lung cancer: A multicenter, adaptive, randomized phase III study (MATISSE). J Clin Oncol. 2017 Aug 10;35(23):2619-2623. Epub 2017 Jun 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01555710
- IMpower133: Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. Epub 2018 Sep 25. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02763579
- PRO analysis: Mansfield AS, Każarnowicz A, Karaseva N, Sánchez A, De Boer R, Andric Z, Reck M, Atagi S, Lee JS, Garassino M, Liu SV, Horn L, Wen X, Quach C, Yu W, Kabbinavar F, Lam S, Morris S, Califano R. Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. Ann Oncol. 2020 Feb;31(2):310-317. Epub 2019 Dec 9. link to original article PubMed
- Update: Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, Garassino MC, De Castro Carpeno J, Califano R, Nishio M, Orlandi F, Alatorre-Alexander J, Leal T, Cheng Y, Lee JS, Lam S, McCleland M, Deng Y, Phan S, Horn L. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021 Feb 20;39(6):619-630. Epub 2021 Jan 13. link to original article link to PMC article PubMed
- CASPIAN: Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. Epub 2019 Oct 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03043872
- PRO analysis: Goldman JW, Garassino MC, Chen Y, Özgüroğlu M, Dvorkin M, Trukhin D, Statsenko G, Hotta K, Ji JH, Hochmair MJ, Voitko O, Havel L, Poltoratskiy A, Losonczy G, Reinmuth N, Patel N, Laud PJ, Shire N, Jiang H, Paz-Ares L. Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study. Lung Cancer. 2020 Nov;149:46-52. Epub 2020 Sep 10. link to original article PubMed
- Update: Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Każarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. Epub 2020 Dec 4. link to original article PubMed
- KEYNOTE-604: Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gümüş M, Kato T, Kalemkerian GP, Luo Y, Ebiana V, Pietanza MC, Kim HR; KEYNOTE-604 Investigators. Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. J Clin Oncol. 2020 Jul 20;38(21):2369-2379. Epub 2020 May 29. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT03066778
- CAPSTONE-1: Wang J, Zhou C, Yao W, Wang Q, Min X, Chen G, Xu X, Li X, Xu F, Fang Y, Yang R, Yu G, Gong Y, Zhao J, Fan Y, Liu Q, Cao L, Yao Y, Liu Y, Li X, Wu J, He Z, Lu K, Jiang L, Hu C, Zhao W, Zhang B, Shi W, Zhang X, Cheng Y; CAPSTONE-1 Study Group. Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022 Jun;23(6):739-747. Epub 2022 May 13. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT03711305
- RATIONALE-312: Cheng Y, Fan Y, Zhao Y, Huang D, Li X, Zhang P, Kang M, Yang N, Zhong D, Wang Z, Yu Y, Zhang Y, Zhao J, Qin T, Chen C, Leaw S, Zheng W, Song Y; RATIONALE-312 Study Group. Tislelizumab Plus Platinum and Etoposide Versus Placebo Plus Platinum and Etoposide as First-Line Treatment for Extensive-Stage SCLC (RATIONALE-312): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 3 Clinical Trial. J Thorac Oncol. 2024 Jul;19(7):1073-1085. Epub 2024 Mar 7. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT04005716
Carboplatin & Etoposide (CE) & Atezolizumab
CE & Atezolizumab: Carboplatin, Etoposide, Atezolizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Horn et al. 2018 (IMpower133) | 2016-06-06 to 2017-05-31 | Phase 3 (E-RT-esc) | CE | Seems to have superior OS1 (co-primary endpoint) Median OS: 12.3 vs 10.3 mo (HR 0.76, 95% CI 0.60-0.95) |
Rudin et al. 2023 (SKYSCRAPER-02) | 2020-02 to 2021-03 | Phase 3 (C) | CE, Atezolizumab, Tiragolumab | Did not meet co-primary endpoints of PFS/OS |
1Reported efficacy for IMpower133 is based on the 2020 update.
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 IV once on day 1
- Etoposide (Vepesid) as follows:
- Cycles 1 to 4: 100 mg/m2 IV once per day on days 1 to 3
Immunotherapy
- Atezolizumab (Tecentriq) 1200 mg IV once on day 1
21-day cycles
References
- IMpower133: Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. Epub 2018 Sep 25. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02763579
- PRO analysis: Mansfield AS, Każarnowicz A, Karaseva N, Sánchez A, De Boer R, Andric Z, Reck M, Atagi S, Lee JS, Garassino M, Liu SV, Horn L, Wen X, Quach C, Yu W, Kabbinavar F, Lam S, Morris S, Califano R. Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. Ann Oncol. 2020 Feb;31(2):310-317. Epub 2019 Dec 9. link to original article PubMed
- Update: Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, Garassino MC, De Castro Carpeno J, Califano R, Nishio M, Orlandi F, Alatorre-Alexander J, Leal T, Cheng Y, Lee JS, Lam S, McCleland M, Deng Y, Phan S, Horn L. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021 Feb 20;39(6):619-630. Epub 2021 Jan 13. link to original article link to PMC article PubMed
- SKYSCRAPER-02: Rudin CM, Liu SV, Soo RA, Lu S, Hong MH, Lee JS, Bryl M, Dumoulin DW, Rittmeyer A, Chiu CH, Ozyilkan O, Johnson M, Navarro A, Novello S, Ozawa Y, Tam SH, Patil NS, Wen X, Huang M, Hoang T, Meng R, Reck M. SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer. J Clin Oncol. 2024 Jan 20;42(3):324-335. Epub 2023 Nov 17. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT04256421
- IMforte: NCT05091567
Carboplatin & Etoposide (CE) & Bevacizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Spigel et al. 2011 (SALUTE) | 2007-2008 | Randomized Phase 2 (E-esc) | 1a. CE 1b. EP |
Seems to have superior PFS (primary endpoint) Median PFS: 5.5 vs 4.4 mo (HR 0.53, 95% CI 0.32-0.86) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Bevacizumab maintenance
References
- SALUTE: Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00403403
Carboplatin & Etoposide (CE) & Durvalumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Paz-Ares et al. 2019 (CASPIAN) | 2017-03-27 to 2018-05-29 | Phase 3 (E-RT-esc) | 1a. CE 1b. EP |
Superior OS1 (primary endpoint) Median OS: 12.9 vs 10.5 mo (HR 0.75, 95% CI 0.62-0.91) |
1Reported efficacy is based on the 2021 update.
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 to 6 IV once on day 1
- Etoposide (Vepesid) as follows:
- Cycles 1 to 4: 80 to 100 mg/m2 IV once per day on days 1 to 3
Immunotherapy
- Durvalumab (Imfinzi) as follows:
- Cycles 1 to 4: 1500 mg IV once on day 1
- Cycle 5 onwards: 1500 mg IV once on day 1
21-day cycle for 4 cycles, then 28-day cycles
References
- CASPIAN: Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. Epub 2019 Oct 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03043872
- PRO analysis: Goldman JW, Garassino MC, Chen Y, Özgüroğlu M, Dvorkin M, Trukhin D, Statsenko G, Hotta K, Ji JH, Hochmair MJ, Voitko O, Havel L, Poltoratskiy A, Losonczy G, Reinmuth N, Patel N, Laud PJ, Shire N, Jiang H, Paz-Ares L. Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study. Lung Cancer. 2020 Nov;149:46-52. Epub 2020 Sep 10. link to original article PubMed
- Update: Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Każarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. Epub 2020 Dec 4. link to original article PubMed
Carboplatin & Etoposide (CE) & Serplulimab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cheng et al. 2022 (ASTRUM-005) | 2019-09-12 to 2021-04-27 | Phase 3 (E-RT-esc) | CE | Superior OS (primary endpoint) Median OS: 15.4 vs 10.9 mo (HR 0.63, 95% CI 0.49-0.82) |
Note: the original capped dose of carboplatin was 800 mg; this was modified in a protocol amendment.
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 (maximum dose of 750 mg) IV once on day 1
- Etoposide (Vepesid) as follows:
- Cycles 1 to 4: 100 mg/m2 IV once per day on days 1 to 3
Immunotherapy
- Serplulimab (Hansizhuang) 4.5 mg/kg IV once on day 1
21-day cycles
References
- ASTRUM-005: Cheng Y, Han L, Wu L, Chen J, Sun H, Wen G, Ji Y, Dvorkin M, Shi J, Pan Z, Shi J, Wang X, Bai Y, Melkadze T, Pan Y, Min X, Viguro M, Li X, Zhao Y, Yang J, Makharadze T, Arkania E, Kang W, Wang Q, Zhu J; ASTRUM-005 Study Group. Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer: The ASTRUM-005 Randomized Clinical Trial. JAMA. 2022 Sep 27;328(12):1223-1232. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT04063163
Carboplatin & Etoposide (CE) & Tislelizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cheng et al. 2024 (RATIONALE-312) | 2019-07-22 to 2021-04-21 | Phase 3 (E-esc) | 1a. CE 1b. EP |
Superior OS (primary endpoint) Median OS: 15.5 vs 13.5 mo (HR 0.75, 95% CI 0.61-0.93) |
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 IV once on day 1
- Etoposide (Vepesid) as follows:
- Cycles 1 to 4: 100 mg/m2 IV once per day on days 1 to 3
Immunotherapy
- Tislelizumab (Baizean) 200 mg IV once on day 1
21-day cycles
References
- RATIONALE-312: Cheng Y, Fan Y, Zhao Y, Huang D, Li X, Zhang P, Kang M, Yang N, Zhong D, Wang Z, Yu Y, Zhang Y, Zhao J, Qin T, Chen C, Leaw S, Zheng W, Song Y; RATIONALE-312 Study Group. Tislelizumab Plus Platinum and Etoposide Versus Placebo Plus Platinum and Etoposide as First-Line Treatment for Extensive-Stage SCLC (RATIONALE-312): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 3 Clinical Trial. J Thorac Oncol. 2024 Jul;19(7):1073-1085. Epub 2024 Mar 7. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT04005716
Carboplatin & Irinotecan
IC: Irinotecan & Carboplatin
IP: Irinotecan & Paraplatin (Carboplatin)
Regimen variant #1, AUC 4/175
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hermes et al. 2008 | 2001-2005 | Phase 3 (E-switch-ic) | CE | Superior OS (primary endpoint) Median OS: 8.5 vs 7.1 mo (HR 0.71, 95% CI 0.53-0.94) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 4 (Chatelut formula) IV once on day 1
- Irinotecan (Camptosar) 175 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Regimen variant #2, AUC 5/150
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schmittel et al. 2006 | 2002-2008 | Randomized Phase 2 (E-switch-ic) | CE | Might have superior OS (secondary endpoint) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1
- Irinotecan (Camptosar) 50 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
Supportive therapy
- 5-HT3 antagonist IV once per day on days 1, 8, 15, prior to chemotherapy
- Loperamide (Imodium) 4 mg PO prn first episode of diarrhea, then 2 mg PO Q2H until diarrhea stops
28-day cycle for up to 6 cycles
References
- Schmittel A, Fischer von Weikersthal L, Sebastian M, Martus P, Schulze K, Hortig P, Reeb M, Thiel E, Keilholz U. A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer. Ann Oncol. 2006 Apr;17(4):663-7. Epub 2006 Jan 19. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Schmittel A, Sebastian M, Fischer von Weikersthal L, Martus P, Gauler TC, Kaufmann C, Hortig P, Fischer JR, Link H, Binder D, Fischer B, Caca K, Eberhardt WE, Keilholz U; Arbeitsgemeinschaft Internistische Onkologie Thoracic Oncology Study Group. A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol. 2011 Aug;22(8):1798-804. Epub 2011 Jan 25. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Hermes A, Bergman B, Bremnes R, Ek L, Fluge S, Sederholm C, Sundstrøm S, Thaning L, Vilsvik J, Aasebø U, Sörenson S. Irinotecan plus carboplatin versus oral etoposide plus carboplatin in extensive small-cell lung cancer: a randomized phase III trial. J Clin Oncol. 2008 Sep 10;26(26):4261-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Carboplatin & Paclitaxel (CP) & Ipilimumab
Regimen variant #1, phased ipilimumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Reck et al. 2012 (CA184-041SCLC) | 2008-2009 | Randomized Phase 2 (E-esc) | 1. CP | Seems to have superior irPFS (primary endpoint) |
2. CP & Ipilimumab; concurrent Ipilimumab | Not reported |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
Immunotherapy
- Ipilimumab (Yervoy) as follows:
- Cycles 3 to 6: 10 mg/kg IV once on day 1
21-day cycle for up to 6 cycles
Subsequent treatment
- Ipilimumab maintenance
Regimen variant #2, concurrent ipilimumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Reck et al. 2012 (CA184-041SCLC) | 2008-2009 | Randomized Phase 2 (E-esc) | 1. CP | Did not meet secondary endpoints |
2. CP & Ipilimumab; phased Ipilimumab | Not reported |
Note: all efficacy endpoints in the ED-SCLC cohort were secondary.
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
Immunotherapy
- Ipilimumab (Yervoy) as follows:
- Cycles 1 to 4: 10 mg/kg IV once on day 1
21-day cycle for up to 6 cycles
Subsequent treatment
- Ipilimumab maintenance
References
- CA184-041SCLC: Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Lu H, Cuillerot JM, Lynch TJ. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol. 2013 Jan;24(1):75-83. Epub 2012 Aug 2. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00527735
Cisplatin & Etoposide (EP)
EP: Etoposide and Platinol (Cisplatin)
PE: Platinol (Cisplatin) and Etoposide
Regimen variant #1, 60/300
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Oh et al. 2016 (COMBAT) | 2009-2013 | Phase 3 (C) | BP | Non-inferior RR |
Note: the total number of planned cycles is not described in the manuscript; total duration information here was provided by the authors.
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
21-day cycle for 4 to 8 cycles
Regimen variant #2, 60/360
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hanna et al. 2006 | 2000-2003 | Phase 3 (C) | Cisplatin & Irinotecan | Did not meet primary endpoint of OS |
Seckl et al. 2017 (LUNGSTAR) | 2007-2012 | Phase 3 (C) | 1a. CE & Pravastatin 1b. EP & Pravastatin |
Did not meet primary endpoint of OS OS24: 14.1% vs 13.2% (HR 0.99, 95% CI 0.86-1.14) |
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 to 3
Supportive therapy
- Per Hanna et al. 2006:
- G-CSF used according to 1999 American Society of Clinical Oncology guidelines
- "Erythropoietin was allowed at the discretion of the treating physician."
21-day cycle for 4 to 6 cycles
Regimen variant #3, 60/440, 1 day of oral etoposide per cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Seckl et al. 2017 (LUNGSTAR) | 2007-2012 | Phase 3 (C) | 1a. CE & Pravastatin 1b. EP & Pravastatin |
Did not meet primary endpoint of OS OS24: 14.1% vs 13.2% (HR 0.99, 95% CI 0.86-1.14) |
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 & 2, then 100 mg PO twice per day on day 3
21-day cycle for up to 6 cycles
Regimen variant #4, 60/520, 2 days of oral etoposide per cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Seckl et al. 2017 (LUNGSTAR) | 2007-2012 | Phase 3 (C) | 1a. CE & Pravastatin 1b. EP & Pravastatin |
Did not meet primary endpoint of OS OS24: 14.1% vs 13.2% (HR 0.99, 95% CI 0.86-1.14) |
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once on day 1, then 100 mg PO twice per day on days 2 & 3
21-day cycle for up to 6 cycles
Regimen variant #5, 70/300
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ruotsalainen et al. 1999 | Not reported in abstract | Phase 3 (C) | EP & IFN-alpha | Did not meet endpoint of OS50% |
Kim et al. 2018 (CRCST-L-0001) | 2006-2011 | Phase 3 (C) | Cisplatin & Irinotecan | Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
21-day cycle for up to 6 cycles
Regimen variant #6, 75/240, split cisplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Okamoto et al. 2007 (JCOG 9702) | 1998-2004 | Phase 3 (C) | CE | Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 25 mg/m2 IV once per day on days 1 to 3
- Etoposide (Vepesid) 80 mg/m2 IV once per day on days 1 to 3
21- to 28-day cycle for 4 cycles
Regimen variant #7, 75/300
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fink et al. 2012 (GSK 104864-A/479) | 2002-2006 | Phase 3 (C) | 1. Cisplatin & Topotecan | Non-inferior OS |
2. Etoposide & Topotecan | Not reported | |||
Spigel et al. 2011 (SALUTE) | 2007-2008 | Randomized Phase 2 (C) | 1a. CE & Bevacizumab 1b. EP & Bevacizumab |
Seems to have inferior PFS |
Reck et al. 2016 (CA184-156) | 2012-2014 | Phase 3 (C) | 1a. CE & Ipilimumab 1b. EP & Ipilimumab |
Did not meet primary endpoint of OS Median OS: 10.9 vs 11 mo (HR 1.06, 95% CI 0.92-1.23) |
Rudin et al. 2020 (KEYNOTE-604) | 2017-05-15 to 2018-07-30 | Phase 3 (C) | 1a. CE & Pembrolizumab 1b. EP & Pembrolizumab |
Seems to have inferior OS |
Cheng et al. 2024 (RATIONALE-312) | 2019-07-22 to 2021-04-21 | Phase 3 (C) | 1a. CE & Tislelizumab 1b. EP & Tislelizumab |
Inferior OS |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
21-day cycle for varying durations: 4 cycles (KEYNOTE-604, RATIONALE-312, SALUTE); 6 cycles (CA184-156, GSK 104864-A/479)
Regimen variant #8, 75/300, split cisplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Evans et al. 1985 | 1981-1984 | Phase 2 | ||
Tiseo et al. 2017 (GOIRC-AIFA FARM6PMFJM) | 2009-2015 | Phase 3 (C) | EP & Bevacizumab | Did not meet primary endpoint of OS Median OS: 9.8 vs 8.9 mo (HR 1.28, 95% CI 0.94-1.72) |
Note: in Evans et al. 1985, patients with disease responding to therapy received prophylactic cranial irradiation, 400 cGy fractions given daily x 5 fractions (total dose: 2000 cGy) over 5 days between cycles 3 and 4; Locoregional radiation therapy was only used if symptoms persisted after 6 cycles of treatment: Radiation therapy, 250 cGy/rad fractions x 10 fractions (total dose: 2500 cGy/rad), given after cycle 6 of chemotherapy.
Chemotherapy
- Cisplatin (Platinol) 25 mg/m2 IV slow push once per day on days 1 to 3, given second
- Etoposide (Vepesid) 100 mg/m2 IV over at least 30 minutes once per day on days 1 to 3, given first
Supportive therapy
- Dexamethasone (Decadron) 10 mg IV once per day on days 1 to 3, prior to chemotherapy
- Metoclopramide (Reglan) 10 mg IV or PO once per day on days 1 to 3, prior to chemotherapy
- Prochlorperazine (Compazine) 10 mg IM or PO once per day on days 1 to 3, prior to chemotherapy
- "No special efforts were made to hydrate the patients," though PO fluid intake was encouraged, and 500 mL normal saline was given with etoposide infusion.
21- to 28-day cycle for up to 6 cycles
Regimen variant #9, 75/390, split cisplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Miller et al. 1995 | 1990-1993 | Phase 3 (C) | EP; oral etoposide | Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 25 mg/m2 IV once per day on days 1 to 3
- Etoposide (Vepesid) 130 mg/m2 IV once per day on days 1 to 3
21-day cycle for 8 cycles
Regimen variant #10, 75/700, 3 days of oral etoposide per cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sundstrøm et al. 2002 | 1989-1994 | Phase 3 (E-switch-ic) | CEV | Did not meet primary endpoint of OS |
Note: Patients in Sundstrøm et al. 2002 with extensive stage disease did not routinely receive radiation therapy. "However, chest or cranial irradiation was optional if severe symptoms could not be palliated by chemotherapy." Oral etoposide to be taken on an empty stomach.
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once on day 1, then 200 mg/m2 PO once per day on days 2 to 4
Supportive therapy
- "Standard prehydration and posthydration procedures were followed in conjunction with cisplatin administration."
21-day cycle for up to 5 cycles
Regimen variant #11, 80/240
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ihde et al. 1994 | 1983-1991 | Phase 3 (C) | EP; high-dose | Did not meet primary endpoint of CR rate |
Niell et al. 2005 (CALGB 9732) | 1998-2001 | Phase 3 (C) | PET | Did not meet endpoints of FFS50%/OS50% |
Note: Concurrent radiation therapy with the start of chemotherapy was given to patients with brain metastases, epidural metastases, and impending pathologic bone fractures.
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Etoposide (Vepesid) 80 mg/m2 IV once per day on days 1 to 3
Supportive therapy
- "Half-normal saline was infused for 2 to 6 hours with cisplatin, usually in conjunction with a diuretic."
- Corticosteroids were usually given for patients receiving radiation therapy for brain and epidural metastases.
21-day cycle for 4 to 8 cycles
CNS therapy
- Patients with carcinomatous meningitis received Methotrexate (MTX) IT (dose/schedule not specified) and radiation to functionally compromised areas of the CNS
Subsequent treatment
- Ihde et al. 1994, CR after 4 cycles: EP continuation x 4 cycles. Some patients were randomized to receive prophylactic cranial irradiation. Radiation could also be given at the patient's request. No details about dose/schedule given.
- Ihde et al. 1994, PR, no response, or progressive disease: Salvage CAV or "an individualized 3-drug in vitro-selected regimen (IVSR) during cycles 5 to 8 if drug-sensitivity testing data were available."
Regimen variant #12, 80/300
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fukuoka et al. 1991 (JCOG8502) | 1985-1988 | Phase 3 (C) | 1. CAV | Not reported |
2. CAV/PE | Might have inferior OS | |||
Miyamoto et al. 1992 | Not reported in abstract | Phase 3 (C) | PEI | Did not meet primary endpoint of OS |
Noda et al. 2002 (JCOG 9511) | 1995-1998 | Phase 3 (C) | IP | Inferior OS |
Eckardt et al. 2006 (GSK 104864-A/389) | 2001-2003 | Phase 3 (C) | Cisplatin & Topotecan | Non-inferior OS |
Lara et al. 2009 (SWOG S0124) | 2002-2007 | Phase 3 (C) | IP | Did not meet primary endpoint of OS |
Baka et al. 2010 | 2002-2006 | Phase 3 (C) | EP/T | Did not meet primary endpoint of OS |
Zatloukal et al. 2010 | 2003-2007 | Phase 3 (C) | IP | Non-inferior OS |
Ready et al. 2015 (CALGB 30504) | 2007-2011 | Non-randomized part of phase 2 RCT | ||
Sun et al. 2016 (D0750018) | 2008-2010 | Phase 3 (C) | Amrubicin & Cisplatin | Might have inferior OS |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
- Alternative scheduling: JCOG8502 & Miyamoto et al. 1992 gave etoposide on days 1, 3, 5
Supportive therapy
- "Hydration and administration of antiemetic drugs."
21-day cycle for 4 to 6 cycles
Subsequent treatment
- Baka et al. 2010: Topotecan consolidation x 4
- CALGB 30504, SD or better: Observation versus sunitinib maintenance
Regimen variant #13, 80/360
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Thatcher et al. 2005 (MRC LU21) | 1996-03 to 2002-02 | Phase 3 (C) | ICE-V | Inferior OS |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 2 & 3, then 240 mg/m2 PO once on day 3
21-day cycle for 6 cycles
Regimen variant #14, 80/400, split cisplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Loehrer et al. 1995 | 1989-1993 | Phase 3 (C) | VIP | Seems to have inferior OS |
Chemotherapy
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 4
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 4
21-day cycle for 4 cycles
Regimen variant #15, 80/600, 2 days of oral etoposide per cycle
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Baka et al. 2008 | 1999-2005 | Phase 3 (E-switch-ic) | ACE | Did not meet primary endpoint of OS12 |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once on day 1, then 240 mg/m2/day PO on days 2 & 3
21-day cycle for 6 cycles
Regimen variant #16, 100/300
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Artal-Cortés et al. 2004 | 1994-1998 | Phase 3 (C) | Cisplatin & Epirubicin | Did not meet primary endpoint of OS |
Pujol et al. 2001 (FNCLCC 95012) | 1996-1999 | Phase 3 (C) | PCDE | Inferior OS |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once on day 2
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
21-day cycle for 6 cycles
Regimen variant #17, 100/400, split cisplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Roth et al. 1992 | 1985-1989 | Phase 3 (C) | 1. CAV 2. CAV/PE |
Did not meet primary endpoint of OS50% |
Hainsworth et al. 1995 | 1992-1993 | Randomized Phase 2 (E-RT-switch-ic) | Cisplatin & Etoposide phosphate | Not compared |
Chemotherapy
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 5
- Etoposide (Vepesid) 80 mg/m2 IV once per day on days 1 to 5
21-day cycle for 4 cycles
References
- Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- JCOG8502: Fukuoka M, Furuse K, Saijo N, Nishiwaki Y, Ikegami H, Tamura T, Shimoyama M, Suemasu K. Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer. J Natl Cancer Inst. 1991 Jun 19;83(12):855-61. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Miyamoto H, Nakabayashi T, Isobe H, Akita H, Kawakami Y, Arimoto T, Asakawa M, Suzuki A, Fujikane T, Shimizu T, Sakai E. A phase III comparison of etoposide/cisplatin with or without added ifosfamide in small-cell lung cancer. Oncology. 1992;49(6):431-5. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Roth BJ, Johnson DH, Einhorn LH, Schacter LP, Cherng NC, Cohen HJ, Crawford J, Randolph JA, Goodlow JL, Broun GO, Omura GA, Greco FA; Southeastern Cancer Study Group. Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol. 1992 Feb;10(2):282-91. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Ihde DC, Mulshine JL, Kramer BS, Steinberg SM, Linnoila RI, Gazdar AF, Edison M, Phelps RM, Lesar M, Phares JC, Grayson J, Minna JD, Johnson BE. Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. J Clin Oncol. 1994 Oct;12(10):2022-34. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Hainsworth JD, Levitan N, Wampler GL, Belani CP, Seyedsadr MS, Randolph J, Schacter LP, Greco FA. Phase II randomized study of cisplatin plus etoposide phosphate or etoposide in the treatment of small-cell lung cancer. J Clin Oncol. 1995 Jun;13(6):1436-42. link to original article PubMed
- Miller AA, Herndon JE 2nd, Hollis DR, Ellerton J, Langleben A, Richards F 2nd, Green MR; CALGB. Schedule dependency of 21-day oral versus 3-day intravenous etoposide in combination with intravenous cisplatin in extensive-stage small-cell lung cancer: a randomized phase III study of the Cancer and Leukemia Group B. J Clin Oncol. 1995 Aug;13(8):1871-9. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Loehrer PJ Sr, Ansari R, Gonin R, Monaco F, Fisher W, Sandler A, Einhorn LH; Hoosier Oncology Group. Cisplatin plus etoposide with and without ifosfamide in extensive small-cell lung cancer: a Hoosier Oncology Group study. J Clin Oncol. 1995 Oct;13(10):2594-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Ruotsalainen TM, Halme M, Tamminen K, Szopinski J, Niiranen A, Pyrhönen S, Riska H, Maasilta P, Jekunen A, Mäntylä M, Kajanti M, Joensuu H, Sarna S, Cantell K, Mattson K. Concomitant chemotherapy and IFN-alpha for small cell lung cancer: a randomized multicenter phase III study. J Interferon Cytokine Res. 1999 Mar;19(3):253-9. link to original article dosing details in abstract have been reviewed by our editors PubMed
- FNCLCC 95012: Pujol JL, Daurès JP, Rivière A, Quoix E, Westeel V, Quantin X, Breton JL, Lemarié E, Poudenx M, Milleron B, Moro D, Debieuvre D, Le Chevalier T. Etoposide plus cisplatin with or without the combination of 4'-epidoxorubicin plus cyclophosphamide in treatment of extensive small-cell lung cancer: a French Federation of Cancer Institutes multicenter phase III randomized study. J Natl Cancer Inst. 2001 Feb 21;93(4):300-8. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00003606
- JCOG 9511: Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, Fukuoka M, Mori K, Watanabe K, Tamura T, Yamamoto S, Saijo N; JCOG. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):85-91. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Artal-Cortés A, Gomez-Codina J, Gonzalez-Larriba JL, Barneto I, Carrato A, Isla D, Camps C, Garcia-Giron C, Font A, Meana A, Lomas M, Vadell C, Arrivi A, Alonso C, Maestu I, Campbell J, Rosell R. Prospective randomized phase III trial of etoposide/cisplatin versus high-dose epirubicin/cisplatin in small-cell lung cancer. Clin Lung Cancer. 2004 Nov;6(3):175-83. link to original article dosing details in abstract have been reviewed by our editors PubMed
- CALGB 9732: Niell HB, Herndon JE 2nd, Miller AA, Watson DM, Sandler AB, Kelly K, Marks RS, Perry MC, Ansari RH, Otterson G, Ellerton J, Vokes EE, Green MR; CALGB. Randomized phase III intergroup trial of etoposide and cisplatin with or without paclitaxel and granulocyte colony-stimulating factor in patients with extensive-stage small-cell lung cancer: Cancer and Leukemia Group B Trial 9732. J Clin Oncol. 2005 Jun 1;23(16):3752-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00003299
- MRC LU21: Thatcher N, Qian W, Clark PI, Hopwood P, Sambrook RJ, Owens R, Stephens RJ, Girling DJ. Ifosfamide, carboplatin, and etoposide with midcycle vincristine versus standard chemotherapy in patients with small-cell lung cancer and good performance status: clinical and quality-of-life results of the British Medical Research Council multicenter randomized LU21 trial. J Clin Oncol. 2005 Nov 20;23(33):8371-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00002822
- Hanna N, Bunn PA Jr, Langer C, Einhorn L, Guthrie T Jr, Beck T, Ansari R, Ellis P, Byrne M, Morrison M, Hariharan S, Wang B, Sandler A. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006 May 1;24(13):2038-43. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- GSK 104864-A/389: Eckardt JR, von Pawel J, Papai Z, Tomova A, Tzekova V, Crofts TE, Brannon S, Wissel P, Ross G. Open-label, multicenter, randomized, phase III study comparing oral topotecan/cisplatin versus etoposide/cisplatin as treatment for chemotherapy-naive patients with extensive-disease small-cell lung cancer. J Clin Oncol. 2006 May 1;24(13):2044-51. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00043927
- JCOG 9702: Okamoto H, Watanabe K, Kunikane H, Yokoyama A, Kudoh S, Asakawa T, Shibata T, Kunitoh H, Tamura T, Saijo N. Randomised phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702. Br J Cancer. 2007 Jul 16;97(2):162-9. Epub 2007 Jun 19. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
- Baka S, Califano R, Ferraldeschi R, Aschroft L, Thatcher N, Taylor P, Faivre-Finn C, Blackhall F, Lorigan P. Phase III randomised trial of doxorubicin-based chemotherapy compared with platinum-based chemotherapy in small-cell lung cancer. Br J Cancer. 2008 Aug 5;99(3):442-7. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed
- SWOG S0124: Lara PN Jr, Natale R, Crowley J, Lenz HJ, Redman MW, Carleton JE, Jett J, Langer CJ, Kuebler JP, Dakhil SR, Chansky K, Gandara DR. Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124. J Clin Oncol. 2009 May 20;27(15):2530-5. Epub 2009 Apr 6. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00045162
- Zatloukal P, Cardenal F, Szczesna A, Gorbunova V, Moiseyenko V, Zhang X, Cisar L, Soria JC, Domine M, Thomas M. A multicenter international randomized phase III study comparing cisplatin in combination with irinotecan or etoposide in previously untreated small-cell lung cancer patients with extensive disease. Ann Oncol. 2010 Sep;21(9):1810-6. Epub 2010 Mar 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00143455
- Baka S, Agelaki S, Kotsakis A, Veslemes M, Papakotoulas P, Agelidou M, Agelidou A, Tsaroucha E, Pavlakou G, Gerogianni A, Androulakis N, Vamvakas L, Kalbakis K, Mavroudis D, Georgoulias V. Phase III study comparing sequential versus alternate administration of cisplatin-etoposide and topotecan as first-line treatment in small cell lung cancer. Anticancer Res. 2010 Jul;30(7):3031-8. link to original article dosing details in abstract have been reviewed by our editors PubMed
- SALUTE: Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00403403
- GSK 104864-A/479: Fink TH, Huber RM, Heigener DF, Eschbach C, Waller C, Steinhauer EU, Virchow JC, Eberhardt F, Schweisfurth H, Schroeder M, Ittel T, Hummler S, Banik N, Bogenrieder T, Acker T, Wolf M; “Aktion Bronchialkarzinom” (ABC Study Group). Topotecan/cisplatin compared with cisplatin/etoposide as first-line treatment for patients with extensive disease small-cell lung cancer: final results of a randomized phase III trial. J Thorac Oncol. 2012 Sep;7(9):1432-9. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00320359
- CALGB 30504: Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, Baggstrom M, Masters GA, Graziano SL, Crawford J, Bogart J, Vokes EE. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: A randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (Alliance). J Clin Oncol. 2015 May 20;33(15):1660-5. Epub 2015 Mar 2. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00453154
- D0750018: Sun Y, Cheng Y, Hao X, Wang J, Hu C, Han B, Liu X, Zhang L, Wan H, Xia Z, Liu Y, Li W, Hou M, Zhang H, Xiu Q, Zhu Y, Feng J, Qin S, Luo X. Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer. BMC Cancer. 2016 Apr 9;16:265. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00660504
- COMBAT: Oh IJ, Kim KS, Park CK, Kim YC, Lee KH, Jeong JH, Kim SY, Lee JE, Shin KC, Jang TW, Lee HK, Lee KY, Lee SY. Belotecan/cisplatin versus etoposide/cisplatin in previously untreated patients with extensive-stage small cell lung carcinoma: a multi-center randomized phase III trial. BMC Cancer. 2016 Aug 26;16:690. link to original article link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00826644
- CA184-156: Reck M, Luft A, Szczesna A, Havel L, Kim SW, Akerley W, Pietanza MC, Wu YL, Zielinski C, Thomas M, Felip E, Gold K, Horn L, Aerts J, Nakagawa K, Lorigan P, Pieters A, Kong Sanchez T, Fairchild J, Spigel D. Phase III randomized trial of ipilimumab plus etoposide and platinum versus placebo plus etoposide and platinum in extensive-stage small-cell lung cancer. J Clin Oncol. 2016 Nov 1;34(31):3740-3748. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01450761
- GOIRC-AIFA FARM6PMFJM: Tiseo M, Boni L, Ambrosio F, Camerini A, Baldini E, Cinieri S, Brighenti M, Zanelli F, Defraia E, Chiari R, Dazzi C, Tibaldi C, Turolla GM, D'Alessandro V, Zilembo N, Trolese AR, Grossi F, Riccardi F, Ardizzoni A. Italian, multicenter, phase III, randomized study of cisplatin plus etoposide with or without bevacizumab as first-line treatment in extensive-disease small-cell lung cancer: the GOIRC-AIFA FARM6PMFJM trial. J Clin Oncol. 2017 Apr 20;35(12):1281-1287. Epub 2017 Jan 30. link to original article dosing details in manuscript have been reviewed by our editors PubMed EudraCT 2007-007949-13
- LUNGSTAR: Seckl MJ, Ottensmeier CH, Cullen M, Schmid P, Ngai Y, Muthukumar D, Thompson J, Harden S, Middleton G, Fife KM, Crosse B, Taylor P, Nash S, Hackshaw A. Multicenter, phase III, randomized, double-blind, placebo-controlled trial of pravastatin added to first-line standard chemotherapy in small-cell lung cancer (LUNGSTAR). J Clin Oncol. 2017 May 10;35(14):1506-1514. Epub 2017 Feb 27. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00433498
- CRCST-L-0001: Kim DW, Kim HG, Kim JH, Park K, Kim HK, Jang JS, Kim BS, Kang JH, Lee KH, Kim SW, Ryoo HM, Kim JS, Lee KH, Kwon JH, Choi JH, Shin SW, Hahn S, Heo DS. Randomized phase III trial of irinotecan plus cisplatin versus etoposide plus cisplatin in chemotherapy-naïve Korean patients with extensive-disease small cell lung cancer. Cancer Res Treat. 2019 Jan;51(1):119-127. Epub 2018 Mar 12. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed NCT00349492
- KEYNOTE-604: Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gümüş M, Kato T, Kalemkerian GP, Luo Y, Ebiana V, Pietanza MC, Kim HR; KEYNOTE-604 Investigators. Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. J Clin Oncol. 2020 Jul 20;38(21):2369-2379. Epub 2020 May 29. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT03066778
- RATIONALE-312: Cheng Y, Fan Y, Zhao Y, Huang D, Li X, Zhang P, Kang M, Yang N, Zhong D, Wang Z, Yu Y, Zhang Y, Zhao J, Qin T, Chen C, Leaw S, Zheng W, Song Y; RATIONALE-312 Study Group. Tislelizumab Plus Platinum and Etoposide Versus Placebo Plus Platinum and Etoposide as First-Line Treatment for Extensive-Stage SCLC (RATIONALE-312): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 3 Clinical Trial. J Thorac Oncol. 2024 Jul;19(7):1073-1085. Epub 2024 Mar 7. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT04005716
Cisplatin & Etoposide (EP) & Bevacizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Spigel et al. 2011 (SALUTE) | 2007-2008 | Randomized Phase 2 (E-esc) | 1a. CE 1b. EP |
Seems to have superior PFS (primary endpoint) Median PFS: 5.5 vs 4.4 mo (HR 0.53, 95% CI 0.32-0.86) |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Bevacizumab maintenance
References
- SALUTE: Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00403403
Cisplatin & Etoposide (EP) & Durvalumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Paz-Ares et al. 2019 (CASPIAN) | 2017-03-27 to 2018-05-29 | Phase 3 (E-RT-esc) | 1a. CE 1b. EP |
Superior OS1 (primary endpoint) Median OS: 12.9 vs 10.5 mo (HR 0.75, 95% CI 0.62-0.91) |
1Reported efficacy is based on the 2021 update.
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 to 4: 75 to 80 mg/m2 IV once on day 1
- Etoposide (Vepesid) as follows:
- Cycles 1 to 4: 80 to 100 mg/m2 IV once per day on days 1 to 3
Immunotherapy
- Durvalumab (Imfinzi) as follows:
- Cycles 1 to 4: 1500 mg IV once on day 1
- Cycle 5 onwards: 1500 mg IV once on day 1
21-day cycle for 4 cycles, then 28-day cycles
References
- CASPIAN: Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. Epub 2019 Oct 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03043872
- PRO analysis: Goldman JW, Garassino MC, Chen Y, Özgüroğlu M, Dvorkin M, Trukhin D, Statsenko G, Hotta K, Ji JH, Hochmair MJ, Voitko O, Havel L, Poltoratskiy A, Losonczy G, Reinmuth N, Patel N, Laud PJ, Shire N, Jiang H, Paz-Ares L. Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study. Lung Cancer. 2020 Nov;149:46-52. Epub 2020 Sep 10. link to original article PubMed
- Update: Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Każarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. Epub 2020 Dec 4. link to original article PubMed
Cisplatin & Etoposide (EP) & Tislelizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cheng et al. 2024 (RATIONALE-312) | 2019-07-22 to 2021-04-21 | Phase 3 (E-esc) | 1a. CE 1b. EP |
Superior OS (primary endpoint) Median OS: 15.5 vs 13.5 mo (HR 0.75, 95% CI 0.61-0.93) |
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 to 4: 75 mg/m2 IV once on day 1
- Etoposide (Vepesid) as follows:
- Cycles 1 to 4: 100 mg/m2 IV once per day on days 1 to 3
Immunotherapy
- Tislelizumab (Baizean) 200 mg IV once on day 1
21-day cycles
References
- RATIONALE-312: Cheng Y, Fan Y, Zhao Y, Huang D, Li X, Zhang P, Kang M, Yang N, Zhong D, Wang Z, Yu Y, Zhang Y, Zhao J, Qin T, Chen C, Leaw S, Zheng W, Song Y; RATIONALE-312 Study Group. Tislelizumab Plus Platinum and Etoposide Versus Placebo Plus Platinum and Etoposide as First-Line Treatment for Extensive-Stage SCLC (RATIONALE-312): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 3 Clinical Trial. J Thorac Oncol. 2024 Jul;19(7):1073-1085. Epub 2024 Mar 7. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT04005716
Cisplatin & Irinotecan (IC)
IP: Irinotecan, Platinol (Cisplatin)
Regimen variant #1, 30/65
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hanna et al. 2006 | 2000-2003 | Phase 3 (E-switch-ic) | Cisplatin & Etoposide | Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV once per day on days 1 & 8
- Irinotecan (Camptosar) 65 mg/m2 IV once per day on days 1 & 8
Supportive therapy
- G-CSF used according to 1999 American Society of Clinical Oncology guidelines
- "Erythropoietin was allowed at the discretion of the treating physician."
21-day cycle for 4 cycles; additional cycles could be given at physician discretion
Regimen variant #2, 60/60
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Noda et al. 2002 (JCOG 9511) | 1995-1998 | Phase 3 (E-switch-ic) | EP | Superior OS (primary endpoint) Median OS: 12.8 vs 9.4 mo (HR 0.60, 95% CI 0.43-0.83) |
Lara et al. 2009 (SWOG S0124) | 2002-2007 | Phase 3 (E-switch-ic) | EP | Did not meet primary endpoint of OS |
Satouchi et al. 2014 (JCOG 0509) | 2007-2010 | Phase 3 (C) | Amrubicin & Cisplatin | Superior OS |
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Irinotecan (Camptosar) 60 mg/m2 IV once per day on days 1, 8, 15
Supportive therapy
- "Hydration and administration of antiemetic drugs."
28-day cycle for 4 cycles
Regimen variant #3, 80/65
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zatloukal et al. 2010 | 2003-2007 | Phase 3 (E-switch-ic) | EP | Non-inferior OS (primary endpoint) Median OS: 10.2 vs 9.7 mo (HR 0.81, 95% CI 0.65-1.01) |
Note: this dosing was the result of a mid-protocol amendment.
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Irinotecan (Camptosar) 65 mg/m2 IV once per day on days 1 & 8
21-day cycle for 6 cycles
References
- JCOG 9511: Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, Fukuoka M, Mori K, Watanabe K, Tamura T, Yamamoto S, Saijo N; JCOG. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):85-91. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Hanna N, Bunn PA Jr, Langer C, Einhorn L, Guthrie T Jr, Beck T, Ansari R, Ellis P, Byrne M, Morrison M, Hariharan S, Wang B, Sandler A. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006 May 1;24(13):2038-43. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- SWOG S0124: Lara PN Jr, Natale R, Crowley J, Lenz HJ, Redman MW, Carleton JE, Jett J, Langer CJ, Kuebler JP, Dakhil SR, Chansky K, Gandara DR. Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124. J Clin Oncol. 2009 May 20;27(15):2530-5. Epub 2009 Apr 6. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00045162
- Zatloukal P, Cardenal F, Szczesna A, Gorbunova V, Moiseyenko V, Zhang X, Cisar L, Soria JC, Domine M, Thomas M. A multicenter international randomized phase III study comparing cisplatin in combination with irinotecan or etoposide in previously untreated small-cell lung cancer patients with extensive disease. Ann Oncol. 2010 Sep;21(9):1810-6. Epub 2010 Mar 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00143455
- JCOG 0509: Satouchi M, Kotani Y, Shibata T, Ando M, Nakagawa K, Yamamoto N, Ichinose Y, Ohe Y, Nishio M, Hida T, Takeda K, Kimura T, Minato K, Yokoyama A, Atagi S, Fukuda H, Tamura T, Saijo N. Phase III study comparing amrubicin plus cisplatin with irinotecan plus cisplatin in the treatment of extensive-disease small-cell lung cancer: JCOG 0509. J Clin Oncol. 2014 Apr 20;32(12):1262-8. Epub 2014 Mar 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed UMIN000000720
Docetaxel monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Hesketh et al. 1999 | Not reported in abstract | Phase 2 |
References
- Hesketh PJ, Crowley JJ, Burris HA 3rd, Williamson SK, Balcerzak SP, Peereboom D, Goodwin JW, Gross HM, Moore DF Jr, Livingston RB, Gandara DR; SWOG. Evaluation of docetaxel in previously untreated extensive-stage small cell lung cancer: a Southwest Oncology Group phase II trial. Cancer J Sci Am. 1999 Jul-Aug;5(4):237-41. dosing details in abstract have been reviewed by our editors PubMed
EP-Topotecan
EP-Topotecan: Etoposide and Platinol (Cisplatin), followed by Topotecan
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ignatiadis et al. 2005 | 2000-2003 | Phase 3 (C) | EP/Topotecan | Did not meet primary endpoint of OS |
Chemotherapy, EP portion (cycles 1 to 4)
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
Chemotherapy, Topotecan portion (cycles 5 to 8)
- Topotecan (Hycamtin) 1.5 mg/m2 IV once per day on days 1 to 5
21-day cycle for 8 cycles
References
- Ignatiadis M, Mavroudis D, Veslemes M, Boukovinas J, Syrigos K, Agelidou M, Agelidou A, Gerogianni A, Pavlakou G, Tselepatiotis E, Nikolakopoulos J, Georgoulias V; Hellenic Oncology Research Group. Sequential versus alternating administration of cisplatin/etoposide and topotecan as first-line treatment in extensive-stage small-cell lung cancer: preliminary results of a Phase III Trial of the Hellenic Oncology Research Group. Clin Lung Cancer. 2005 Nov;7(3):183-9. link to original article dosing details in abstract have been reviewed by our editors PubMed
Ifosfamide monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Ettinger et al. 2002 (ECOG E1588) | 1988-1990 | Phase 3 (E-switch-ic) | 1. CAV | Did not meet primary endpoint of OS | Less toxic |
2. Teniposide | Did not meet primary endpoint of OS | Not reported |
Chemotherapy
- Ifosfamide (Ifex) 1500 mg/m2 IV once per day on days 1 to 5
Supportive therapy
- Mesna (Mesnex) 300 mg/m2 IV three times per day on days 1 to 5, given 0, 4, and 8 hours after each dose of ifosfamide (total dose per cycle: 4500 mg/m2)
21-day cycle for 4 to 6 cycles
Subsequent treatment
- ECOG E1588, patients with CR: Ifosfamide continuation x 2 cycles, then prophylactic whole-brain irradiation if still in CR
- ECOG E1588, patients with PR: Ifosfamide continuation until progression of disease, then salvage EP
References
- ECOG E1588: Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; ECOG. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
IVE
IVE: Ifosfamide, VP-16 (Etoposide), Epirubicin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Berghmans et al. 2017 (ELCWP 01994) | 2000-2013 | Phase 3 (C) | EP | Did not meet primary endpoint of OS |
Note: This combination is based on a commonly used backbone in Europe. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
Chemotherapy
- Ifosfamide (Ifex) 1500 mg/m2 IV once per day on days 1 to 3
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
Supportive therapy
- Mesna (Mesnex) 300 mg/m2 IV once on day 1, given just before ifosfamide, then 300 mg/m2 IV once every 4 hours for 72 hours (total dose per cycle: 5700 mg/m2)
21-day cycles
References
- ELCWP 01994: Berghmans T, Scherpereel A, Meert AP, Giner V, Lecomte J, Lafitte JJ, Leclercq N, Paesmans M, Sculier JP; European Lung Cancer Working Party (ELCWP). A Phase III Randomized Study Comparing a Chemotherapy with Cisplatin and Etoposide to a Etoposide Regimen without Cisplatin for Patients with Extensive Small-Cell Lung Cancer. Front Oncol. 2017 Sep 19;7:217. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00658580
Teniposide monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Ettinger et al. 2002 (ECOG E1588) | 1988-1990 | Phase 3 (E-switch-ic) | 1. CAV | Did not meet primary endpoint of OS | Less toxic |
2. Ifosfamide | Did not meet primary endpoint of OS | Not reported |
Chemotherapy
- Teniposide (Vumon) 60 mg/m2 IV once per day on days 1 to 5
21-day cycle for 4 to 6 cycles
Subsequent treatment
- ECOG E1588, patients with CR after 4 to 6 cycles: Teniposide continuation x 2 cycles
- ECOG E1588, patients with CR after 6 to 8 cycles: prophylactic whole-brain irradiation
- ECOG E1588, patients with PR: Teniposide continuation until progression of disease, then salvage EP
References
- ECOG E1588: Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; ECOG. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Extensive stage, consolidation after first-line therapy
Whole brain irradiation
PCI: Prophylactic Cranial Irradiation
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ettinger et al. 2002 (ECOG E1588) | 1988-1990 | Non-randomized part of phase 3 RCT | ||
Slotman et al. 2007 (EORTC 22993) | 2001-2006 | Phase 3 (E-esc) | Observation | Superior OS (secondary endpoint) Median OS: 6.7 vs 5.4 mo (HR 0.68, 95% CI 0.52-0.88) |
Preceding treatment
- ECOG E1588: CAV versus Ifosfamide versus Teniposide
- EORTC 22993: Chemotherapy x 4 to 6 cycles (regimen not specified)
Radiotherapy
- Whole brain irradiation by one of the following: 2000 cGy in 5 or 8 fractions, 2400 cGy in 12 fractions, 2500 cGy in 10 fractions, or 3000 cGy in 10 or 12 fractions
1- to 3-week course
References
- Meta-analysis: Aupérin A, Arriagada R, Pignon JP, Le Péchoux C, Gregor A, Stephens RJ, Kristjansen PE, Johnson BE, Ueoka H, Wagner H, Aisner J; Prophylactic Cranial Irradiation Overview Collaborative Group. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med. 1999 Aug 12;341(7):476-84. link to original article PubMed
- ECOG E1588: Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; ECOG. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- EORTC 22993: Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, Postmus P, Collette L, Musat E, Senan S; EORTC Radiation Oncology Group; EORTC Lung Cancer Group. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007 Aug 16;357(7):664-72. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00016211
Extensive stage, maintenance after first-line therapy
Bevacizumab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Spigel et al. 2011 (SALUTE) | 2007-2008 | Non-randomized part of phase 2 RCT |
Preceding treatment
- CE & Bevacizumab induction x 4 or EP & Bevacizumab induction x 4
References
- Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00403403
Ipilimumab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Reck et al. 2012 (CA184-041SCLC) | 2008-2009 | Non-randomized part of phase 2 RCT |
Preceding treatment
- Carboplatin, Paclitaxel, Ipilimumab induction
References
- CA184-041SCLC: Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Lu H, Cuillerot JM, Lynch TJ. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol. 2013 Jan;24(1):75-83. Epub 2012 Aug 2. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00527735
Sunitinib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ready et al. 2015 (CALGB 30504) | 2007-2011 | Randomized Phase 2 (E-esc) | Observation | Seems to have superior PFS (primary endpoint) Median PFS: 3.7 vs 2.1 mo (HR 0.62, 95% CI 0.38-0.98) |
Preceding treatment
- Carboplatin & Etoposide or Cisplatin & Etoposide for 4 to 6 cycles
Targeted therapy
- Sunitinib (Sutent) as follows:
- Cycle 1: 150 mg PO once on day 1, then 37.5 mg PO once per day on days 2 to 28
- Cycle 2 onwards: 37.5 mg PO once per day on days 1 to 28
28-day cycles
References
- CALGB 30504: Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, Baggstrom M, Masters GA, Graziano SL, Crawford J, Bogart J, Vokes EE. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: A randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (Alliance). J Clin Oncol. 2015 May 20;33(15):1660-5. Epub 2015 Mar 2. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00453154
Relapsed or refractory disease, second-line
Amrubicin monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Pawel et al. 2014 (ACT-1) | 2007-2010 | Phase 3 (E-switch-ic) | Topotecan | Did not meet primary endpoint of OS Median OS: 7.5 vs 7.8 mo (HR 0.88, 95% CI 0.73-1.06) |
Spigel et al. 2021 (CheckMate 331) | 2015-2017 | Phase 3 (C) | Nivolumab | Might have inferior OS |
Chemotherapy
- Amrubicin (Calsed) 40 mg/m2 IV over 5 minutes once per day on days 1 to 3
Supportive therapy
- "Prophylactic antibiotics were recommended for patients at high risk of infectious complications."
21-day cycle for at least 6 cycles
References
- ACT-1: von Pawel J, Jotte R, Spigel DR, O'Brien ME, Socinski MA, Mezger J, Steins M, Bosquée L, Bubis J, Nackaerts K, Trigo JM, Clingan P, Schütte W, Lorigan P, Reck M, Domine M, Shepherd FA, Li S, Renschler MF. Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. J Clin Oncol. 2014 Dec 10;32(35):4012-9. Epub 2014 Nov 10. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00547651
- CheckMate 331: Spigel DR, Vicente D, Ciuleanu TE, Gettinger S, Peters S, Horn L, Audigier-Valette C, Pardo Aranda N, Juan-Vidal O, Cheng Y, Zhang H, Shi M, Luft A, Wolf J, Antonia S, Nakagawa K, Fairchild J, Baudelet C, Pandya D, Doshi P, Chang H, Reck M. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331. Ann Oncol. 2021 May;32(5):631-641. Epub 2021 Feb 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02481830
Carboplatin & Etoposide (CE)
EC: Etoposide & Carboplatin
EP: Etoposide & Paraplatin (Carboplatin)
CE: Carboplatin & Etoposide
Ca/E: Carboplatin & Etoposide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Baize et al. 2020 (GFPC 01-2013) | 2013-2018 | Phase 3 (E-switch-ic) | Topotecan | Superior PFS (primary endpoint) Median PFS: 4.7 vs 2.7 mo (HR 0.57, 90% CI 0.41-0.73) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
21-day cycle for 6 cycles
References
- GFPC 01-2013: Baize N, Monnet I, Greillier L, Geier M, Lena H, Janicot H, Vergnenegre A, Crequit J, Lamy R, Auliac JB, Letreut J, Le Caer H, Gervais R, Dansin E, Madroszyk A, Renault PA, Le Garff G, Falchero L, Berard H, Schott R, Saulnier P, Chouaid C; Groupe Français de Pneumo-Cancérologie. Carboplatin plus etoposide versus topotecan as second-line treatment for patients with sensitive relapsed small-cell lung cancer: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2020 Sep;21(9):1224-1233. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02738346
Cisplatin, Etoposide, Irinotecan
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Goto et al. 2016 (JCOG0605) | 2007-2012 | Phase 3 (E-esc) | Topotecan | Superior OS (primary endpoint) Median OS: 18.2 vs 12.5 mo (HR 0.67, 90% CI 0.51-0.88) |
Chemotherapy
- Cisplatin (Platinol) 25 mg/m2 IV over 60 minutes once per day on days 1 & 8
- Etoposide (Vepesid) 60 mg/m2 IV over 60 minutes once per day on days 1 to 3
- Irinotecan (Camptosar) 90 mg/m2 IV over 90 minutes once on day 8
Supportive therapy
- G-CSF, started on cycle 1 day 9: (dose not specified) SC once per day, continued throughout except for days of chemotherapy
14-day cycle for 5 cycles
References
- JCOG0605: Goto K, Ohe Y, Shibata T, Seto T, Takahashi T, Nakagawa K, Tanaka H, Takeda K, Nishio M, Mori K, Satouchi M, Hida T, Yoshimura N, Kozuki T, Imamura F, Kiura K, Okamoto H, Sawa T, Tamura T; JCOG. Combined chemotherapy with cisplatin, etoposide, and irinotecan versus topotecan alone as second-line treatment for patients with sensitive relapsed small-cell lung cancer (JCOG0605): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1147-57. Epub 2016 Jun 14. link to original article dosing details in manuscript have been reviewed by our editors PubMed UMIN000000828
Lurbinectedin monotherapy
Regimen
Study | Dates of enrollment | Evidence | Efficacy |
---|---|---|---|
Trigo et al. 2020 (PM1183-B-005-14) | 2015-2019 | Phase 2 (RT) | ORR: 35.2% (95% CI, 26.2-45.2%) |
Chemotherapy
- Lurbinectedin (Zepzelca) 3.2 mg/m2 IV over 60 minutes once on day 1
Supportive therapy
- "All patients received antiemetic prophylaxis."
21-day cycles
References
- PM1183-B-005-14: Trigo J, Subbiah V, Besse B, Moreno V, López R, Sala MA, Peters S, Ponce S, Fernández C, Alfaro V, Gómez J, Kahatt C, Zeaiter A, Zaman K, Boni V, Arrondeau J, Martínez M, Delord JP, Awada A, Kristeleit R, Olmedo ME, Wannesson L, Valdivia J, Rubio MJ, Anton A, Sarantopoulos J, Chawla SP, Mosquera-Martinez J, D'Arcangelo M, Santoro A, Villalobos VM, Sands J, Paz-Ares L. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020 May;21(5):645-654. link to original article dosing details in manuscript have been reviewed by our editors Epub 2020 Mar 27. PubMed NCT02454972
Relapsed or refractory disease, subsequent lines
This section includes studies that do not specify an exact line or have yet to be categorized.
Bendamustine monotherapy
Regimen
Study | Dates of enrollment | Evidence | Efficacy |
---|---|---|---|
Lammers et al. 2014 (VICC THO 0920) | 2009-2012 | Phase 2 | ORR: 33% (95% CI, 14-52%) |
References
- VICC THO 0920: Lammers PE, Shyr Y, Li CI, Hutchison AS, Sandler A, Carbone DP, Johnson DH, Keedy VL, Horn L. Phase II study of bendamustine in relapsed chemotherapy sensitive or resistant small-cell lung cancer. J Thorac Oncol. 2014 Apr;9(4):559-62. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00984542
CAV
CAV: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine
Regimen variant #1, no capping
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Aix et al. 2022 (ATLANTIS) | 2016-2018 | Phase 3 (C) | Doxorubicin & Lurbinectedin | Did not meet primary endpoint of OS Median OS: 7.6 vs 8.6 mo (HR 1.03, 95% CI 0.87-1.22) |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
21-day cycle for up to 10 cycles
Regimen variant #2, capped
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Pawel et al. 1999 | Not reported | Phase 3 (C) | Topotecan | Did not meet co-primary endpoints of ORR/DOR |
Note: von Pawel et al. 1999 does not clearly state the duration of each cycle, but 21 days is used in other CAV regimens, and there was no information in the paper that contradicted this.
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 (maximum dose of 2000 mg) (route not specified) once on day 1
- Doxorubicin (Adriamycin) 45 mg/m2 (maximum dose of 100 mg) IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
Supportive therapy
- G-CSF use per physician discretion
21-day cycle for up to 6 cycles beyond maximal response Patients with stable disease after 4 cycles could have treatment discontinued at physician discretion.
Regimen variant #3
Study | Dates of enrollment | Evidence |
---|---|---|
Ihde et al. 1994 | 1983-1991 | Non-randomized part of phase 3 RCT |
Note: Ihde et al. 1994 did not specifically say that the three medications were all given on day 1, but this is assumed to be the case based on other CAV regimens.
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
21-day cycle for 4 cycles
References
- Ihde DC, Mulshine JL, Kramer BS, Steinberg SM, Linnoila RI, Gazdar AF, Edison M, Phelps RM, Lesar M, Phares JC, Grayson J, Minna JD, Johnson BE. Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. J Clin Oncol. 1994 Oct;12(10):2022-34. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, Stewart DJ, Clark PI, Palmer MC, Depierre A, Carmichael J, Krebs JB, Ross G, Lane SR, Gralla R. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999 Feb;17(2):658-67. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- ATLANTIS: Aix SP, Ciuleanu TE, Navarro A, Cousin S, Bonanno L, Smit EF, Chiappori A, Olmedo ME, Horvath I, Grohé C, Farago AF, López-Vilariño JA, Cullell-Young M, Nieto A, Vasco N, Gómez J, Kahatt C, Zeaiter A, Carcereny E, Roubec J, Syrigos K, Lo G, Barneto I, Pope A, Sánchez A, Kattan J, Zarogoulidis K, Waller CF, Bischoff H, Juan-Vidal O, Reinmuth N, Dómine M, Paz-Ares L. Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial. Lancet Respir Med. 2023 Jan;11(1):74-86. Epub 2022 Oct 14. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02566993
Cisplatin & Etoposide (EP)
EP: Etoposide, Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
O'Bryan et al. 1990 (SWOG S8215) | Not reported | Phase 3 (E-switch-ic) | BTOC | Did not meet efficacy endpoints |
Ettinger et al. 2002 (ECOG E1588) | 1988-1990 | Non-randomized part of phase 3 RCT |
Preceding treatment
- ECOG E1588: CAV versus ifosfamide versus teniposide, with progression
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 to 3
21-day cycles
References
- SWOG S8215: O'Bryan RM, Crowley JJ, Kim PN, Epstein RB, Neilan B, Coltman CA Jr, Stuckey WJ, Pazdur R. Comparison of etoposide and cisplatin with bis-chloro-ethylnitrosourea, thiotepa, vincristine, and cyclophosphamide for salvage treatment in small cell lung cancer: a Southwest Oncology Group Study. Cancer. 1990 Feb 15;65(4):856-60. link to original article PubMed
- ECOG E1588: Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; ECOG. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Docetaxel monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Smyth et al. 1994 | Not reported | Phase 2 |
References
- Smyth JF, Smith IE, Sessa C, Schoffski P, Wanders J, Franklin H, Kaye SB; Early Clinical Trials Group of the EORTC. Activity of docetaxel (Taxotere) in small cell lung cancer. Eur J Cancer. 1994;30A(8):1058-60. link to original article dosing details in abstract have been reviewed by our editors PubMed
Epirubicin & Ifosfamide
EI: Epirubicin, Ifosfamide
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Jacot et al. 2012 | 1992-2010 | Phase 2 |
Chemotherapy
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Ifosfamide (Ifex) 3000 mg/m2 IV once per day on days 1 & 2
Supportive therapy
- Mesna (Mesnex) (dose/route/schedule not specified) on days 1 & 2
- G-CSF use per physician discretion
28-day cycle for up to 6 cycles
References
- Jacot W, Pujol JL, Chakra M, Molinier O, Bozonnat MC, Gervais R, Quantin X. Epirubicin and ifosfamide in relapsed or refractory small cell lung cancer patients. Lung Cancer. 2012 Feb;75(2):213-6. Epub 2011 Aug 9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Etoposide monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Einhorn et al. 1990 | Not reported in abstract | Phase 2 |
Johnson et al. 1990 | 1988-07 to 1990-01 | Phase 2 |
Chemotherapy
- Etoposide (Vepesid) 50 mg/m2 PO once per day on days 1 to 21, taken on an empty stomach
21-day cycles
References
- Einhorn LH, Pennington K, McClean J; Hoosier Oncology Group. Phase II trial of daily oral VP-16 in refractory small cell lung cancer: a Hoosier Oncology Group study. Semin Oncol. 1990 Feb;17(1 Suppl 2):32-5. Not available online; abstract contains protocol PubMed
- Johnson DH, Greco FA, Strupp J, Hande KR, Hainsworth JD. Prolonged administration of oral etoposide in patients with relapsed or refractory small-cell lung cancer: a phase II trial. J Clin Oncol. 1990 Oct;8(10):1613-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Gemcitabine monotherapy
Regimen variant #1, 5 cycles
Study | Dates of enrollment | Evidence |
---|---|---|
van der Lee et al. 2001 | 1997-02 to 1998-11 | Phase 2 |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for up to 5 cycles
Regimen variant #2, indefinite
Study | Dates of enrollment | Evidence |
---|---|---|
Masters et al. 2003 (ECOG E1597) | 1997-12-05 to 1998-09-04 | Phase 2 |
Note: dose escalation was carried out if patients had less than grade 2 toxicity with cycle 1.
Chemotherapy
- Gemcitabine (Gemzar) as follows:
- Cycle 1: 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
- Cycle 2 onwards: 1250 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
References
- van der Lee I, Smit EF, van Putten JW, Groen HJ, Schlösser NJ, Postmus PE, Schramel FM. Single-agent gemcitabine in patients with resistant small-cell lung cancer. Ann Oncol. 2001 Apr;12(4):557-61. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- ECOG E1597: Masters GA, Declerck L, Blanke C, Sandler A, DeVore R, Miller K, Johnson D; ECOG. Phase II trial of gemcitabine in refractory or relapsed small-cell lung cancer: Eastern Cooperative Oncology Group Trial 1597. J Clin Oncol. 2003 Apr 15;21(8):1550-5. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Ifosfamide monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Cantwell et al. 1988 | Not reported | Phase 2 |
Chemotherapy
- Ifosfamide (Ifex) 5000 mg/m2 IV once on day 1
Supportive therapy
- Mesna (Mesnex) 5000 mg/m2 IV once on day 1
21-day cycles
References
- Cantwell BM, Bozzino JM, Corris P, Harris AL. The multidrug resistant phenotype in clinical practice; evaluation of cross resistance to ifosfamide and mesna after VP16-213, doxorubicin and vincristine (VPAV) for small cell lung cancer. Eur J Cancer Clin Oncol. 1988 Feb;24(2):123-9. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Review: Marangolo M, Giovanis P. Ifosfamide in small cell lung cancer. Oncology. 2003;65 Suppl 2:46-9. Review. link to original article PubMed
Ifosfamide & Paclitaxel
PI: Paclitaxel, Ifosfamide
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Park et al. 2007a | 2002-10 to 2006-03 | Phase 2 |
Chemotherapy
- Ifosfamide (Ifex) 2500 mg/m2 IV over 2 hours once per day on days 1 & 2
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
Supportive therapy
- Mesna (Mesnex) 500 mg/m2 IV three times per day on days 1 & 2, given 15 minutes before, 4 hours after, and 8 hours after ifosfamide (total dose per cycle: 3000 mg/m2)
21-day cycles
References
- Park S, Ahn MJ, Ahn JS, Lee J, Hong YS, Park BB, Lee SC, Hwang IG, Park JO, Lim H, Kang WK, Park K. Combination chemotherapy with paclitaxel and ifosfamide as the third-line regimen in patients with heavily pretreated small cell lung cancer. Lung Cancer. 2007 Oct;58(1):116-22. Epub 2007 Jul 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Irinotecan monotherapy
Regimen variant #1, weekly
Study | Dates of enrollment | Evidence |
---|---|---|
Masuda et al. 1992 | Not reported | Phase 2, fewer than 20 pts |
Chemotherapy
- Irinotecan (Camptosar) 100 mg/m2 IV over 90 minutes once per day on days 1, 8, 15
Supportive therapy
- No routine prophylaxis against diarrhea, nausea, or vomiting used.
21-day cycles
Regimen variant #2, q3wk
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Edelman et al. 2022 (DISTINCT) | 2017 to not reported | Phase 3 (C) | 1. Irinotecan & Dinutuximab | Did not meet primary endpoint of OS Median OS: 7 vs 6.9 mo |
2. Topotecan | Not reported |
References
- Masuda N, Fukuoka M, Kusunoki Y, Matsui K, Takifuji N, Kudoh S, Negoro S, Nishioka M, Nakagawa K, Takada M. CPT-11: a new derivative of camptothecin for the treatment of refractory or relapsed small-cell lung cancer. J Clin Oncol. 1992 Aug;10(8):1225-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- DISTINCT: Edelman MJ, Dvorkin M, Laktionov K, Navarro A, Juan-Vidal O, Kozlov V, Golden G, Jordan O, Deng CQ, Bentsion D, Chouaid C, Dechev H, Dowlati A, Fernández Núñez N, Ivashchuk O, Kiladze I, Kortua T, Leighl N, Luft A, Makharadze T, Min Y, Quantin X; DISTINCT study investigators. Randomized phase 3 study of the anti-disialoganglioside antibody dinutuximab and irinotecan vs irinotecan or topotecan for second-line treatment of small cell lung cancer. Lung Cancer. 2022 Apr;166:135-142. Epub 2022 Mar 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03098030
Paclitaxel monotherapy
Regimen variant #1, every 3 weeks
Study | Dates of enrollment | Evidence |
---|---|---|
Smit et al. 1998 | 1994-12 to 1996-06 | Phase 2 |
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
Supportive therapy
- Dexamethasone (Decadron) 8 mg PO given twice on day 1; 12 and 6 hours prior to paclitaxel
- Clemastine (Tavist) 2 mg IV push once on day 1; 30 minutes prior to paclitaxel
- One of the following H2 blockers:
- Cimetidine (Tagamet) 300 mg IV push once on day 1; 30 minutes prior to paclitaxel
- Ranitidine (Zantac) 50 mg IV push once on day 1; 30 minutes prior to paclitaxel
21-day cycle for up to 5 cycles
Regimen variant #2, weekly paclitaxel
Study | Dates of enrollment | Evidence |
---|---|---|
Yamamoto et al. 2006 | 1999-12 to 2002-02 | Phase 2 |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36
Supportive therapy
- Dexamethasone (Decadron) 20 mg IV once per day on days 1, 8, 15, 22, 29, 36; 30 minutes prior to paclitaxel
- Ranitidine (Zantac) 50 mg IV once per day on days 1, 8, 15, 22, 29, 36; 30 minutes prior to paclitaxel
- Diphenhydramine (Benadryl) 50 mg IV once per day on days 1, 8, 15, 22, 29, 36; 30 minutes prior to paclitaxel
- If ANC less than 1000/μL or WBC count less than 2 x 109/L, G-CSF (type not specified) 2 mcg/kg SC once per day is given until WBC count more than or equal to 10 x 109/L, except on days that paclitaxel is given
8-week cycles
References
- Smit EF, Fokkema E, Biesma B, Groen HJ, Snoek W, Postmus PE. A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer. Br J Cancer. 1998;77(2):347-51. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
- Yamamoto N, Tsurutani J, Yoshimura N, Asai G, Moriyama A, Nakagawa K, Kudoh S, Takada M, Minato Y, Fukuoka M. Phase II study of weekly paclitaxel for relapsed and refractory small cell lung cancer. Anticancer Res. 2006 Jan-Feb;26(1B):777-81. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Tarlatamab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Ahn et al. 2023 (DeLLphi-301) | 2021-12 to 2023-05 | Phase 2 (RT) |
Immunotherapy
- Tarlatamab (Imdelltra) as follows:
- Cycle 1: 1 mg IV over 60 minutes once on day 1, then 10 mg IV once on day 8
- Cycle 2 onwards: 10 mg IV once on day 1
14-day cycles
References
- DeLLphi-301: Ahn MJ, Cho BC, Felip E, Korantzis I, Ohashi K, Majem M, Juan-Vidal O, Handzhiev S, Izumi H, Lee JS, Dziadziuszko R, Wolf J, Blackhall F, Reck M, Bustamante Alvarez J, Hummel HD, Dingemans AC, Sands J, Akamatsu H, Owonikoko TK, Ramalingam SS, Borghaei H, Johnson ML, Huang S, Mukherjee S, Minocha M, Jiang T, Martinez P, Anderson ES, Paz-Ares L; DeLLphi-301 Investigators. Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. N Engl J Med. 2023 Nov 30;389(22):2063-2075. Epub 2023 Oct 20. link to original article PubMed NCT05060016
Temozolomide monotherapy
Regimen variant #1, 75 mg/m2/d, 21 out of 28 days
Study | Dates of enrollment | Evidence |
---|---|---|
Pietanza et al. 2012 | 2008-2010 | Phase 2 |
Chemotherapy
- Temozolomide (Temodar) 75 mg/m2 PO once per day on days 1 to 21 (no food within 2 hours before or 1 hour after temozolomide)
Supportive therapy
- Ondansetron (Zofran) 8 mg PO once per day on days 1 to 21, taken prior to temozolomide prn nausea
- Patients with at least grade 3 lymphopenia received prophylaxis for Pneumocystis carinii pneumonia (no specific medication/dose/schedule listed)
28-day cycles
Regimen variant #2, 200 mg/m2/d, 5 out of 28 days
Study | Dates of enrollment | Evidence |
---|---|---|
Zauderer et al. 2014 (MSKCC 08-065) | Not reported | Phase 2 |
Chemotherapy
- Temozolomide (Temodar) 200 mg/m2 PO once per day on days 1 to 5
Supportive therapy
- Ondansetron (Zofran) 8 mg PO once per day on days 1 to 5; 30 minutes prior to temozolomide
28-day cycles
References
- Pietanza MC, Kadota K, Huberman K, Sima CS, Fiore JJ, Sumner DK, Travis WD, Heguy A, Ginsberg MS, Holodny AI, Chan TA, Rizvi NA, Azzoli CG, Riely GJ, Kris MG, Krug LM. Phase II trial of temozolomide in patients with relapsed sensitive or refractory small cell lung cancer, with assessment of methylguanine-DNA methyltransferase as a potential biomarker. Clin Cancer Res. 2012 Feb 15;18(4):1138-45. Epub 2012 Jan 6. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- MSKCC 08-065: Zauderer MG, Drilon A, Kadota K, Huberman K, Sima CS, Bergagnini I, Sumner DK, Travis WD, Heguy A, Ginsberg MS, Holodny AI, Riely GJ, Kris MG, Krug LM, Pietanza MC. Trial of a 5-day dosing regimen of temozolomide in patients with relapsed small cell lung cancers with assessment of methylguanine-DNA methyltransferase. Lung Cancer. 2014 Nov;86(2):237-40. Epub 2014 Aug 17. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00740636
Topotecan monotherapy
Regimen variant #1, 1 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Goto et al. 2016 (JCOG0605) | 2007-2012 | Phase 3 (C) | Cisplatin, Etoposide, Irinotecan | Inferior OS |
Chemotherapy
- Topotecan (Hycamtin) 1 mg/m2 IV over 30 minutes once per day on days 1 to 5
21-day cycle for 4 cycles
Regimen variant #2, 1.5 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Pawel et al. 1999 | Not reported | Phase 3 (E-RT-de-esc) | CAV | Did not meet co-primary endpoints of ORR/DOR |
Eckardt et al. 2007 | 1999-2001 | Phase 3 (C) | Topotecan; oral | Did not meet primary endpoint of ORR |
von Pawel et al. 2014 (ACT-1) | 2007-2010 | Phase 3 (C) | Amrubicin | Did not meet primary endpoint of OS |
Spigel et al. 2021 (CheckMate 331) | 2015-2017 | Phase 3 (C) | Nivolumab | Might have inferior OS |
Aix et al. 2022 (ATLANTIS) | 2016-2018 | Phase 3 (C) | Doxorubicin & Lurbinectedin | Did not meet primary endpoint of OS Median OS: 7.6 vs 8.6 mo (HR 1.03, 95% CI 0.87-1.22) |
Blackhall et al. 2021 (TAHOE) | 2017-04-11 to 2018-12-07 | Phase 3 (C) | Rovalpituzumab tesirine | Superior OS (primary endpoint) Median OS: 8.6 vs 6.3 mo (HR 0.68, 95% CI 0.55-0.85) |
Edelman et al. 2022 (DISTINCT) | 2017 to not reported | Phase 3 (C) | 1. Irinotecan & Dinutuximab | Did not meet primary endpoint of OS Median OS: 7.4 vs 6.9 mo |
2. Irinotecan | Not reported | |||
Spigel et al. 2024 (RESILIENT Par 2) | 2019-08 to 2021-02 | Phase 3 (C) | Liposomal irinotecan | Did not meet primary endpoint of OS Median OS: 8.3 vs 7.9 mo (HR 0.90, 95% CI 0.73-1.11) |
Chemotherapy
- Topotecan (Hycamtin) 1.5 mg/m2 IV over 30 minutes once per day on days 1 to 5
Supportive therapy
- (varies depending on reference):
- G-CSF use per physician discretion
- In von Pawel et al. 2014 (ACT-1), "Prophylactic antibiotics were recommended for patients at high risk of infectious complications."
21-day cycles Duration varies depending on reference:
- In von Pawel et al. 1999 treatment is given until progression of disease, unacceptable toxicity, or 6 cycles beyond maximal response. Patients with stable disease after 4 cycles could have treatment discontinued at physician discretion.
- In Eckardt et al. 2007, patients with complete or partial response continued treatment progression of disease or 2 cycles beyond best response. Patients with stable disease received at least 4 cycles therapy.
- In ACT-1, treatment was given for 6 cycles or until progression of disease. Patients who had at least stable disease by cycle 6 could receive another 6 cycles of treatment.
Regimen variant #3, oral route
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Eckardt et al. 2007 | 1999-2001 | Phase 3 (E-switch-ic) | Topotecan; IV (1.5 mg/m2) | Did not meet primary endpoint of ORR |
O'Brien et al. 2006 (GSK 104864/478) | 2000-2004 | Phase 3 (E-esc) | Best supportive care | Seems to have superior OS (primary endpoint) |
Baize et al. 2020 (GFPC 01-2013) | 2013-2018 | Phase 3 (C) | Carboplatin & Etoposide | Inferior PFS |
Spigel et al. 2021 (CheckMate 331) | 2015-2017 | Phase 3 (C) | Nivolumab | Might have inferior OS |
Note: Duration of treatment details vary depending on reference. In GSK 104864/478, treatment is given for at least 4 cycles, though this depended on tolerability and response. In Eckardt et al. 2007, patients with complete or partial response continued treatment progression of disease or 2 cycles beyond best response. Patients with stable disease received at least 4 cycles of therapy. Patients enrolled in GFPC 01-2013 received 6 cycles.
Chemotherapy
- Topotecan (Hycamtin) 2.3 mg/m2 PO once per day on days 1 to 5
21-day cycle for varying durations: indefinitely (GFPC 01-2013); 4 or more cycles (see note)
References
- von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, Stewart DJ, Clark PI, Palmer MC, Depierre A, Carmichael J, Krebs JB, Ross G, Lane SR, Gralla R. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999 Feb;17(2):658-67. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- GSK 104864/478: O'Brien ME, Ciuleanu TE, Tsekov H, Shparyk Y, Cuceviá B, Juhasz G, Thatcher N, Ross GA, Dane GC, Crofts T. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol. 2006 Dec 1;24(34):5441-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00276276
- Eckardt JR, von Pawel J, Pujol JL, Papai Z, Quoix E, Ardizzoni A, Poulin R, Preston AJ, Dane G, Ross G. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol. 2007 May 20;25(15):2086-92. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- ACT-1: von Pawel J, Jotte R, Spigel DR, O'Brien ME, Socinski MA, Mezger J, Steins M, Bosquée L, Bubis J, Nackaerts K, Trigo JM, Clingan P, Schütte W, Lorigan P, Reck M, Domine M, Shepherd FA, Li S, Renschler MF. Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. J Clin Oncol. 2014 Dec 10;32(35):4012-9. Epub 2014 Nov 10. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00547651
- JCOG0605: Goto K, Ohe Y, Shibata T, Seto T, Takahashi T, Nakagawa K, Tanaka H, Takeda K, Nishio M, Mori K, Satouchi M, Hida T, Yoshimura N, Kozuki T, Imamura F, Kiura K, Okamoto H, Sawa T, Tamura T; JCOG. Combined chemotherapy with cisplatin, etoposide, and irinotecan versus topotecan alone as second-line treatment for patients with sensitive relapsed small-cell lung cancer (JCOG0605): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1147-57. Epub 2016 Jun 14. link to original article dosing details in manuscript have been reviewed by our editors PubMed UMIN000000828
- GFPC 01-2013: Baize N, Monnet I, Greillier L, Geier M, Lena H, Janicot H, Vergnenegre A, Crequit J, Lamy R, Auliac JB, Letreut J, Le Caer H, Gervais R, Dansin E, Madroszyk A, Renault PA, Le Garff G, Falchero L, Berard H, Schott R, Saulnier P, Chouaid C; Groupe Français de Pneumo-Cancérologie. Carboplatin plus etoposide versus topotecan as second-line treatment for patients with sensitive relapsed small-cell lung cancer: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2020 Sep;21(9):1224-1233. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT02738346
- CheckMate 331: Spigel DR, Vicente D, Ciuleanu TE, Gettinger S, Peters S, Horn L, Audigier-Valette C, Pardo Aranda N, Juan-Vidal O, Cheng Y, Zhang H, Shi M, Luft A, Wolf J, Antonia S, Nakagawa K, Fairchild J, Baudelet C, Pandya D, Doshi P, Chang H, Reck M. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331. Ann Oncol. 2021 May;32(5):631-641. Epub 2021 Feb 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02481830
- TAHOE: Blackhall F, Jao K, Greillier L, Cho BC, Penkov K, Reguart N, Majem M, Nackaerts K, Syrigos K, Hansen K, Schuette W, Cetnar J, Cappuzzo F, Okamoto I, Erman M, Langer SW, Kato T, Groen H, Sun Z, Luo Y, Tanwani P, Caffrey L, Komarnitsky P, Reinmuth N. Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE Study. J Thorac Oncol. 2021 Sep;16(9):1547-1558. Epub 2021 Feb 16. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT03061812
- DISTINCT: Edelman MJ, Dvorkin M, Laktionov K, Navarro A, Juan-Vidal O, Kozlov V, Golden G, Jordan O, Deng CQ, Bentsion D, Chouaid C, Dechev H, Dowlati A, Fernández Núñez N, Ivashchuk O, Kiladze I, Kortua T, Leighl N, Luft A, Makharadze T, Min Y, Quantin X; DISTINCT study investigators. Randomized phase 3 study of the anti-disialoganglioside antibody dinutuximab and irinotecan vs irinotecan or topotecan for second-line treatment of small cell lung cancer. Lung Cancer. 2022 Apr;166:135-142. Epub 2022 Mar 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03098030
- ATLANTIS: Aix SP, Ciuleanu TE, Navarro A, Cousin S, Bonanno L, Smit EF, Chiappori A, Olmedo ME, Horvath I, Grohé C, Farago AF, López-Vilariño JA, Cullell-Young M, Nieto A, Vasco N, Gómez J, Kahatt C, Zeaiter A, Carcereny E, Roubec J, Syrigos K, Lo G, Barneto I, Pope A, Sánchez A, Kattan J, Zarogoulidis K, Waller CF, Bischoff H, Juan-Vidal O, Reinmuth N, Dómine M, Paz-Ares L. Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial. Lancet Respir Med. 2023 Jan;11(1):74-86. Epub 2022 Oct 14. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02566993
- RESILIENT Part 2: Spigel DR, Dowlati A, Chen Y, Navarro A, Yang JC, Stojanovic G, Jove M, Rich P, Andric ZG, Wu YL, Rudin CM, Chen H, Zhang L, Yeung S, Benzaghou F, Paz-Ares L, Bunn PA; RESILIENT Trial Investigators. RESILIENT Part 2: A Randomized, Open-Label Phase III Study of Liposomal Irinotecan Versus Topotecan in Adults With Relapsed Small Cell Lung Cancer. J Clin Oncol. 2024 Jul 1;42(19):2317-2326. Epub 2024 Apr 22. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03088813
Vinorelbine monotherapy
Regimen variant #1, 25 mg/m2
Study | Dates of enrollment | Evidence |
---|---|---|
Furuse et al. 1996a | Not reported in abstract | Phase 2 |
Regimen variant #2, 30 mg/m2
Study | Dates of enrollment | Evidence |
---|---|---|
Jassem et al. 1993 | 1990-06 to 1991-05 | Phase 2 |
References
- Jassem J, Karnicka-Mlodkowska H, van Pottelsberghe C, van Glabbeke M, Noseda MA, Ardizzoni A, Gozzelino F, Planting A, van Zandwijk N; EORTC Lung Cancer Cooperative Group. Phase II study of vinorelbine (Navelbine) in previously treated small cell lung cancer patients. Eur J Cancer. 1993;29A(12):1720-2. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Furuse K, Kubota K, Kawahara M, Takada M, Kimura I, Fujii M, Ohta M, Hasegawa K, Yoshida K, Nakajima S, Ogura T, Niitani H; Japan Lung Cancer Vinorelbine Study Group. Phase II study of vinorelbine in heavily previously treated small cell lung cancer. Oncology. 1996 Mar-Apr;53(2):169-72. link to original article dosing details in abstract have been reviewed by our editors PubMed