Difference between revisions of "Staging page"

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[[#top|Back to Top]]
 
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</div>
 
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{{#lst:Section editor transclusions|thoracic}}
 
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''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!''.
 
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{| class="wikitable" style="float:right; margin-right: 5px;"
 
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|-
 
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|<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>
 
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<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>
 
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|}
 
−
{{TOC limit|limit=3}}
 
−
=Guidelines=
 
−
==[http://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]
 
−
*'''2020:''' Schneider et al. [https://doi.org/10.1200/jco.19.02748 Lung Cancer Surveillance After Definitive Curative-Intent Therapy: ASCO Guideline]
 
−
*'''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]
 
−
==[http://www.esmo.org/ 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]
 
−
===Older===
 
−
*'''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]
 
−
==[https://www.nccn.org/ NCCN]==
 
−
*[https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf NCCN Guidelines - Small Cell Lung Cancer]
 
−
=Limited stage, induction=
 
−
==Carboplatin & Etoposide (CE) {{#subobject:f0013f|Regimen=1}}==
 
−
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%"|Years 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://academic.oup.com/jnci/article-lookup/doi/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
 
−
|-
 
−
|}
 
−
<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====
 
−
*Patients with complete or partial responses: [[#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%"|Years 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://academic.oup.com/jnci/article-lookup/doi/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
 
−
|-
 
−
|}
 
−
<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====
 
−
*Patients with complete or partial responses: [[#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://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djp200 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19608997 PubMed] 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%"|Years 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
 
−
|-
 
−
|}
 
−
''Patients with limited stage disease responding to therapy received [[#Whole_brain_irradiation|prophylactic cranial irradiation]], 4 Gy fractions once per day x 5 fractions (total dose: 20 Gy) over 5 days between cycles 3 and 4.''
 
−
====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====
 
−
*[[#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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2997406 PubMed]
 
−
=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
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:9e4385|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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]
 
−
|1993-1999
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
 
−
|[[#Carboplatin.2C_Etoposide.2C_RT|Carboplatin, Etoposide, RT]]; early HTRT
 
−
| style="background-color:#d9ef8b" |Might have superior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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'''
 
−
====Radiotherapy====
 
−
*Concurrent [[External beam radiotherapy|hyperfractionated thoracic radiation therapy (HTRT)]], 1.5 Gy fractions given twice per day (at least 4, but preferably 6 hours between fractions) x 30 fractions (total dose: 45 Gy) 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'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with CR: [[#Whole_brain_irradiation|Prophylactic cranial irradiation]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:bb6fc|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1999.17.11.3540 Okamoto et al. 1999]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Patients in Okamoto et al. 1999 were greater than or equal to 70 years old.''
 
−
====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
 
−
====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
 
−
*[[: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'''
 
−
</div></div>
 
−
===References===
 
−
<!-- 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. [https://doi.org/10.1200/jco.1999.17.11.3540 link to original article] '''contains dosing details in manuscript''' [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; 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] '''contains dosing details in manuscript''' [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
 
−
<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%"|Years 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]], 1.5 Gy fractions given twice per day x 30 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 45 Gy)
 
−
'''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 [[#Whole_brain_irradiation|Prophylactic 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%"|Years 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
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
====Radiotherapy====
 
−
*Concurrent [[External_beam_radiotherapy|radiation therapy]], 2.1 Gy fractions x 25 fractions over 5 weeks, given during cycle 1 of chemotherapy (total dose: 52.5 Gy)
 
−
'''21-day cycle for 4 cycles'''
 
−
</div></div><br>
 
−
<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%"|Years 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 (E-switch-ic)
 
−
|[[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]]; early RT
 
−
| style="background-color:#eeee01" |Non-inferior CR rate
 
−
| 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]], 2.1 Gy fractions x 25 fractions over 5 weeks, given during cycle 3 of chemotherapy (total dose: 52.5 Gy)
 
−
'''21-day cycle for 4 cycles'''
 
−
</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%"|Years 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====
 
−
*[[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
 
−
*[[Etoposide (Vepesid)]] as follows:
 
−
**Cycles 1 to 3: 60 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
**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, 1.8 Gy fractions x 25 fractions (total dose: 45 Gy)
 
−
'''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%"|Years 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)]
 
−
|2008-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#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">
 
−
====Chemotherapy====
 
−
*[[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
 
−
====Radiotherapy====
 
−
*Concurrent [[External_beam_radiotherapy|radiation therapy]], 1.5 Gy fractions given twice per day x 30 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 45 Gy)
 
−
'''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;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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)]
 
−
|2008-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#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">
 
−
====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
 
−
====Radiotherapy====
 
−
*Concurrent [[External_beam_radiotherapy|radiation therapy]], 1.5 Gy fractions given twice per day x 30 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 45 Gy)
 
−
'''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
 
−
!style="width: 20%"|Years 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.2002.12.111 Sundstrøm et al. 2002]
 
−
|1989-1994
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[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
 
−
*[[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
 
−
====Radiotherapy====
 
−
*Concurrent [[External_beam_radiotherapy|thoracic radiation therapy]], 2.8 Gy fractions once per day x 15 fractions (total dose: 42 Gy) 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'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with CR: [[#Whole_brain_irradiation|Prophylactic cranial irradiation]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #8, 80/240/50 {{#subobject:d203ec|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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://insights.ovid.com/pubmed?pmid=15685040 McClay et al. 2005 (CALGB 9235)]
 
−
|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">
 
−
====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
 
−
====Radiotherapy====
 
−
*Concurrent [[External_beam_radiotherapy|thoracic radiation therapy]], 200 cGy fractions once per day x 25 fractions (total dose: 50 Gy) 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
 
−
!style="width: 33%"|Years 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/S1470204513705114 Kubota et al. 2013 (JCOG0202)]
 
−
|2002-2006
 
−
| style="background-color:#91cf61" |Non-randomized portion 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
 
−
====Radiotherapy====
 
−
*Concurrent [[External_beam_radiotherapy|thoracic radiation therapy]], 1.5 Gy fractions given twice per day (at least 4, but preferably 6 hours between fractions) x 30 fractions (total dose: 45 Gy) over 3 weeks, started on cycle 1 day 2 of chemotherapy
 
−
'''28-day cycle for 1 cycle'''
 
−
</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%"|Years 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)]
 
−
|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
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
====Radiotherapy====
 
−
*Concurrent [[External_beam_radiotherapy|thoracic radiation therapy]], 1.5 Gy fractions given twice per day (4 or more hours between fractions) x 30 fractions (total dose: 45 Gy) 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"): [[#Whole_brain_irradiation|Prophylactic 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%"|Years 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]], 2.66 Gy fractions once per day x 15 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 39.9 Gy)
 
−
'''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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12118018 PubMed] content property of [http://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] '''contains dosing details in manuscript''' [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://insights.ovid.com/pubmed?pmid=15685040 link to original article] '''contains dosing details in abstract''' [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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23592701 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; [[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/S1470204513705114 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24309370 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. [https://doi.org/10.1016/S1470204517303182 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555437/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28642008 PubMed] NCT00433563
 
−
#'''CALGB 30610:''' 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%"|Years 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_99|Cisplatin & Irinotecan]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|}
 
−
<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] '''contains dosing details in manuscript''' [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" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.07.1605 Saito et al. 2006 (WJTOG 9902)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Cisplatin.2C_Etoposide.2C_RT|Cisplatin, Etoposide, RT]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
====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====
 
−
*Patients with complete or good partial responses: [[#Whole_brain_irradiation|Prophylactic 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] '''contains dosing details in manuscript''' [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%"|Years 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====
 
−
*[[#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: 25 Gy)
 
−
</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] '''contains dosing details in manuscript''' [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://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djp200 link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/19608997 PubMed] 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, 20 Gy {{#subobject:900486|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://jamanetwork.com/journals/jama/fullarticle/373562 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 portion 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: [[#Cisplatin_.26_Etoposide_.28EP.29|EP]] x 3
 
−
*Skarlos et al. 2001: [[#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]], 4 Gy fractions once per day x 5 fractions (total dose: 20 Gy)
 
−
'''1-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Evans et al. 1985: [[#Cisplatin_.26_Etoposide_.28EP.29|EP]] x 3
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 24 Gy {{#subobject:5b88f0|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2002.12.071 Takada et al. 2002 (JCOG 9104)]
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]] versus [[#Cisplatin_.26_Etoposide_.28EP.29|EP]], then [[#Radiation_therapy|RT]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Radiotherapy====
 
−
*[[External beam radiotherapy|Whole brain irradiation]], 1.5 Gy fractions given twice per day x 16 fractions (total dose: 24 Gy)
 
−
'''2-week course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 25 Gy {{#subobject:1475db|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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 portion 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: [[#Cisplatin.2C_Etoposide.2C_RT|EP & once-daily RT]] versus [[#Cisplatin.2C_Etoposide.2C_RT|EP & twice-daily RT]]
 
−
*WJTOG 9902: [[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]], then [[#Cisplatin_.26_Irinotecan_.28IC.29|IP]] x 3
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Radiotherapy====
 
−
*[[External beam radiotherapy|Whole brain irradiation]], 2.5 Gy fractions x 10 fractions (total dose: 25 Gy)
 
−
'''2-week course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 30 Gy {{#subobject:63970e|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2002.12.111 Sundstrøm et al. 2002]
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[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]], 2 Gy fractions once per day x 15 fractions (total dose: 30 Gy)
 
−
'''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://jamanetwork.com/journals/jama/fullarticle/373562 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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12118018 PubMed] content property of [http://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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [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] 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%"|Years 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
 
−
|-
 
−
|}
 
−
''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===
 
−
# '''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27566413 PubMed] NCT00826644
 
−
==Carboplatin & Etoposide (CE) {{#subobject:de3ba6|Regimen=1}}==
 
−
CE: '''<u>C</u>'''arboplatin & '''<u>E</u>'''toposide
 
−
<br>EP: '''<u>E</u>'''toposide & '''<u>P</u>'''araplatin (Carboplatin)
 
−
<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%"|Years 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">
 
−
====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
 
−
'''21-day cycle for 4 cycles'''
 
−
</div></div><br>
 
−
<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%"|Years 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 (E-switch-ic)
 
−
|[[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]; split-dose
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://www.clinical-lung-cancer.com/article/S1525-7304(13)00232-5 Sekine et al. 2013 (D0702002)]
 
−
|2006-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Amrubicin_monotherapy_99|Amrubicin]]
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
 
−
*[[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 4 to 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, AUC 5/300 {{#subobject:1eba05|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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)]
 
−
|2006-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Carboplatin_.26_Pemetrexed_99|Carboplatin & Pemetrexed]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.29.3423 Spigel et al. 2011 (SALUTE)]
 
−
|2007-2008
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|1. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Bevacizumab|CE & Bevacizumab]]<br>2. [[#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 portion 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)
 
−
|[[Stub#Carboplatin_.26_Etoposide_.28CE.29_.26_Ipilimumab|CE & Ipilimumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[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_99|PaCE]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1809064 Horn et al. 2018 (IMpower133)]
 
−
|2016-2017
 
−
|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>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(19)32222-6 Paz-Ares et al. 2019 (CASPIAN)]
 
−
|2017-2018
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Durvalumab|CE & Durvalumab]]<br> 2. [[#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)]
 
−
|2017-2018
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[Small_cell_lung_cancer_-_historical#Carboplatin_.26_Etoposide_.28CE.29_.26_Pembrolizumab|CE & Pembrolizumab]]<br> 2. [[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_77|CE & Adebrelimab]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
''<sup>1</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====
 
−
*[[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
 
−
====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 4 to 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*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 #4, AUC 5 or 6/360 {{#subobject:927150|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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)
 
−
|1. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_99|CE & Pravastatin]]<br>2. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_99|EP & Pravastatin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Carboplatin (Paraplatin)]] AUC 5 or 6 (maximum dose of 1000 mg) IV once on day 1
 
−
**AUC 5 is used if eGFR calculated by EDTA; AUC 6 is used if eGFR calculated by Cockcroft Gault. If eGFR greater than 130 mL/min/1.73m<sup>2</sup>, dose calculation to be capped at GFR = 130 mL/min/1.73m<sup>2</sup>
 
−
*[[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 #5, AUC 5/420 {{#subobject:69fffb|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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://journals.lww.com/amjclinicaloncology/Abstract/2009/02000/Multicenter_Randomized_Open_Label_Phase_III_Study.13.aspx 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
 
−
|-
 
−
|}
 
−
<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 #6, AUC 5 or 6/440, 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%"|Years 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://academic.oup.com/jnci/article-lookup/doi/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
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ Seckl et al. 2017 (LUNGSTAR)]
 
−
|2007-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_99|CE & Pravastatin]]<br>2. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_99|EP & Pravastatin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Carboplatin (Paraplatin)]] AUC 5 or 6 (maximum dose of 1000 mg) IV once on day 1
 
−
**'''LLCG-STUDY-12''': AUC 5 is used
 
−
**'''LUNGSTAR''': AUC 5 is used if eGFR calculated by EDTA; AUC 6 is used if eGFR calculated by Cockcroft Gault. If eGFR greater than 130 mL/min/1.73m<sup>2</sup>, dose calculation to be capped at GFR = mL/min/1.73m<sup>2</sup>
 
−
*[[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 #7, AUC 5 or 6/520, 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%"|Years 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://academic.oup.com/jnci/article-lookup/doi/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
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ Seckl et al. 2017 (LUNGSTAR)]
 
−
|2007-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_99|CE & Pravastatin]]<br>2. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_99|EP & Pravastatin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Carboplatin (Paraplatin)]] AUC 5 or 6 (maximum dose of 1000 mg) IV once on day 1
 
−
**'''LLCG-STUDY-12''': AUC 5 is used
 
−
**'''LUNGSTAR''': AUC 5 is used if eGFR calculated by EDTA; AUC 6 is used if eGFR calculated by Cockcroft Gault. If eGFR greater than 130 mL/min/1.73m<sup>2</sup>, dose calculation to be capped at GFR = mL/min/1.73m<sup>2</sup>
 
−
*[[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 #8, AUC 5/300, 28-day cycles {{#subobject:d904aa|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1999.17.11.3540 Okamoto et al. 1999]
 
−
|1995-1996
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|[https://doi.org/10.1023/a:1011171722175 Quoix et al. 2001]
 
−
|1997-1999
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Patients in Okamoto et al. 1999 and Quoix et al. 2001 were greater than or equal to 70 years old.''
 
−
====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'''
 
−
====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 4 to 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Palliative radiation therapy was allowed to control persistent pain from bony metastases
 
−
</div></div>
 
−
===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. [https://doi.org/10.1200/jco.1999.17.11.3540 link to original article] '''contains dosing details in manuscript''' [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. [https://doi.org/10.1023/a:1011171722175 link to original article] '''contains dosing details in manuscript''' [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. [https://doi.org/10.1093/annonc/mdj137 link to original article] '''contains dosing details in manuscript''' [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. [https://doi.org/10.1093/annonc/mdq652 link to original article] '''contains dosing details in manuscript''' [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://www.nature.com/articles/6603810 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360311/ link to PMC article] '''contains dosing details in abstract''' [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] '''contains dosing details in abstract''' [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://journals.lww.com/amjclinicaloncology/Abstract/2009/02000/Multicenter_Randomized_Open_Label_Phase_III_Study.13.aspx link to original article] '''contains dosing details in abstract''' [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://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djp200 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19608997 PubMed] 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. -->
 
−
# '''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19720897 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. [https://doi.org/10.1200/JCO.2010.29.3423 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21502556 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. [https://www.clinical-lung-cancer.com/article/S1525-7304(13)00232-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24361248 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. [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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25732163 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. [https://doi.org/10.1200/JCO.2016.67.6601 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27458307 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. [https://doi.org/10.1200/JCO.2016.69.7391 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28240967 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. [https://doi.org/10.1200/JCO.2016.71.7454 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28605291 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. [https://doi.org/10.1056/NEJMoa1809064 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30280641 PubMed] NCT02763579
 
−
## '''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://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] [https://pubmed.ncbi.nlm.nih.gov/31590988 PubMed] NCT03043872
 
−
##'''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32468956/ 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. [https://doi.org/10.1016/s1470-2045(22)00224-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/35576956/ PubMed] NCT03711305
 
−
==Carboplatin & Etoposide (CE) & Atezolizumab {{#subobject:760b97|Regimen=1}}==
 
−
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%"|Years 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)]
 
−
|2016-2017
 
−
|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><br>Median OS: 12.3 vs 10.3 mo<br>(HR 0.76, 95% CI 0.60-0.95)
 
−
|-
 
−
|}
 
−
''<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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30280641 PubMed] NCT02763579
 
−
## '''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://pubmed.ncbi.nlm.nih.gov/33439693/ PubMed]
 
−
#'''IMforte:''' NCT05091567
 
−
==Carboplatin & Etoposide (CE) & Bevacizumab {{#subobject:d61f26|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:3eed0d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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.2010.29.3423 Spigel et al. 2011 (SALUTE)]
 
−
|2007-2008
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|1. [[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]<br>2. [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS
 
−
|-
 
−
|}
 
−
<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
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
'''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21502556 PubMed] 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%"|Years 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)]
 
−
|2017-2018
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|1. [[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]<br> 2. [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><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)]] 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] [https://pubmed.ncbi.nlm.nih.gov/31590988 PubMed] NCT03043872
 
−
##'''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%"|Years 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/10.1001/jama.2022.16464 Cheng et al. 2022 (ASTRUM-005)]
 
−
|2019-2021
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 15.4 vs 10.9 mo<br>(HR 0.63, 95% CI 0.49-0.82)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Carboplatin (Paraplatin)]]
 
−
*[[Etoposide (Vepesid)]]
 
−
====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] '''contains partial dosing information in abstract''' [https://pubmed.ncbi.nlm.nih.gov/36166026/ PubMed] NCT04063163
 
−
==Carboplatin & Irinotecan {{#subobject:b2ac71|Regimen=1}}==
 
−
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%"|Years 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<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====
 
−
*[[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'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===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%"|Years 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]
 
−
|2002-2008
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
 
−
|[[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 1
 
−
*[[Irinotecan (Camptosar)]] 50 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
 
−
====Supportive therapy====
 
−
*[[: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
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===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. [https://doi.org/10.1093/annonc/mdj137 link to original article] '''contains dosing details in manuscript''' [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. [https://doi.org/10.1093/annonc/mdq652 link to original article] '''contains dosing details in manuscript''' [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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18779613 PubMed]
 
−
==Carboplatin & Paclitaxel (CP) & Ipilimumab {{#subobject:9695b3|Regimen=1}}==
 
−
<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%"|Years 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)]
 
−
|rowspan=2|2008-2009
 
−
| rowspan="2" style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_88|CP]]
 
−
| style="background-color:#91cf60" |Seems to have superior irPFS
 
−
|-
 
−
|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====
 
−
*[[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:
 
−
**Cycles 3 to 6: 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><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%"|Years 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)]
 
−
|rowspan=2|2008-2009
 
−
| rowspan="2" style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_88|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:#d3d3d3" |Not reported
 
−
|-
 
−
|}
 
−
''Note: all efficacy endpoints in the ED-SCLC cohort were secondary.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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:
 
−
**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===
 
−
# '''CA184-041:''' 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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22858559 PubMed] NCT00527735
 
−
==Cisplatin & Etoposide (EP) {{#subobject:ec90cd|Regimen=1}}==
 
−
EP: '''<u>E</u>'''toposide and '''<u>P</u>'''latinol (Cisplatin)
 
−
<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%"|Years 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%"|Years 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)
 
−
|1. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_99|CE & Pravastatin]]<br>2. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_99|EP & Pravastatin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of 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
 
−
====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%"|Years 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)
 
−
|1. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_99|CE & Pravastatin]]<br>2. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_99|EP & Pravastatin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of 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 & 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%"|Years 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)
 
−
|1. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_99|CE & Pravastatin]]<br>2. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_99|EP & Pravastatin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of 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 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 #5, 70/300 {{#subobject:5b9a41|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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.liebertpub.com/doi/abs/10.1089/107999099314180 Ruotsalainen et al. 1999]
 
−
|NR in abstract
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cisplatin_.26_Etoposide_.28EP.29_.26_Interferon_alfa_99|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)]
 
−
|2006-2011
 
−
| 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
 
−
|-
 
−
|}
 
−
<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%"|Years 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">
 
−
====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
 
−
'''21- to 28-day cycle for 4 cycles'''
 
−
</div></div><br>
 
−
<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%"|Years 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.clinical-lung-cancer.com/article/S1525-7304(11)70409-0/pdf Ignatiadis et al. 2005]
 
−
|2000-2003
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cisplatin_.26_Etoposide_.28EP.29.2FTopotecan_monotherapy_99|EP/Topotecan]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|rowspan=2|[https://www.jto.org/article/S1556-0864(15)32944-0 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_88|Cisplatin & Topotecan]]
 
−
| style="background-color:#eeee01" |Non-inferior OS
 
−
|-
 
−
|2. [[#Etoposide_.26_Topotecan_99|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)
 
−
|1. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Bevacizumab|CE & Bevacizumab]]<br>2. [[#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)
 
−
|[[Stub#EP_.26_Ipilimumab|EP & Ipilimumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ Rudin et al. 2020 (KEYNOTE-604)]
 
−
|2017-2018
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[Small_cell_lung_cancer_-_historical#Carboplatin_.26_Etoposide_.28CE.29_.26_Pembrolizumab|CE & Pembrolizumab]]<br> 2. [[Small_cell_lung_cancer_-_historical#Cisplatin_.26_Etoposide_.28EP.29_.26_Pembrolizumab|EP & Pembrolizumab]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
'''21-day cycle for 4 (SALUTE & KEYNOTE-604) or 6 (GSK 104864-A/479 & CA184-156) cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===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%"|Years 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.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_99|EP & Bevacizumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: in Evans et al. 1985, patients with disease responding to therapy received prophylactic cranial irradiation, 4 Gy fractions given daily x 5 fractions (total dose: 20 Gy) 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%"|Years 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]
 
−
|1990-1993
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#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====
 
−
*[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
*[[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;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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.2002.12.111 Sundstrøm et al. 2002]
 
−
|1989-1994
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[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." 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
 
−
*[[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====
 
−
*"Standard prehydration and posthydration procedures were followed in conjunction with cisplatin administration."
 
−
'''21-day cycle for up to 5 cycles'''
 
−
</div></div><br>
 
−
<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;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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.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_99|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 (Platinol)]], 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
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Ihde et al. 1994, CR after 4 cycles: an additional 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%"|Years 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://academic.oup.com/jnci/article-abstract/83/12/855/956642 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://www.karger.com/Article/Abstract/227087 Miyamoto et al. 1992]
 
−
|NR 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_88|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
 
−
|-
 
−
|[http://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_99|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 portion 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)]
 
−
|2008-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Amrubicin_.26_Cisplatin_88|Amrubicin & Cisplatin]]
 
−
| style="background-color:#fee08b" |Might have 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)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
**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'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Baka et al. 2010: [[#Topotecan_monotherapy_88|Topotecan]] 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, 80/400, split cisplatin {{#subobject:d389d3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #14, 80/600, 2 days of oral etoposide per cycle {{#subobject:998892|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/PMC2527803/ Baka et al. 2008]
 
−
|1999-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Small_cell_lung_cancer_-_historical#ACE|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 #15, 100/300 {{#subobject:5b54c7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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.clinical-lung-cancer.com/article/S1525-7304(11)70217-0/pdf Artal-Cortés et al. 2004]
 
−
|1994-1998
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cisplatin_.26_Epirubicin_99|Cisplatin & Epirubicin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://academic.oup.com/jnci/article/93/4/300/2906465 Pujol et al. 2001 (FNCLCC 95012)]
 
−
|1996-1999
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Small_cell_lung_cancer_-_historical#PCDE|PCDE]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 2
 
−
*[[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 #16, 100/400, split cisplatin {{#subobject:f8e87a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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.1992.10.2.282 Roth et al. 1992]
 
−
|1985-1989
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|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%
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1995.13.6.1436 Hainsworth et al. 1995]
 
−
|1992-1993
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-RT-switch-ic)
 
−
|[[#Cisplatin_.26_Etoposide_phosphate_88|Cisplatin & Etoposide phosphate]]
 
−
| style="background-color:#d3d3d3" |Not compared
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
*[[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>
 
−
===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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2997406 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. [https://academic.oup.com/jnci/article-abstract/83/12/855/956642 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/1648142 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. [https://www.karger.com/Article/Abstract/227087 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/1334539 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. [https://doi.org/10.1200/JCO.1992.10.2.282 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1310103 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. [https://doi.org/10.1200/jco.1994.12.10.2022 link to original article] '''contains dosing details in manuscript''' [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] '''contains dosing details in abstract''' [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] '''contains dosing details in manuscript''' [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://www.liebertpub.com/doi/abs/10.1089/107999099314180 link to original article] '''contains dosing details in abstract''' [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://academic.oup.com/jnci/article/93/4/300/2906465 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11181777 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; [[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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [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://www.clinical-lung-cancer.com/article/S1525-7304(11)70217-0/pdf link to original article] '''contains dosing details in abstract''' [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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15923572 PubMed] NCT00003299
 
−
# 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://www.clinical-lung-cancer.com/article/S1525-7304(11)70409-0/pdf link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16354313 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. -->
 
−
# 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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16648503 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. [https://doi.org/10.1200/JCO.2005.03.3332 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16648504 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. [https://www.nature.com/articles/6603810 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360311/ link to PMC article] '''contains dosing details in abstract''' [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://www.nature.com/articles/6604480 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527803/ link to PMC article] '''contains dosing details in abstract''' [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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19349543 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. [https://doi.org/10.1093/annonc/mdq036 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20231298 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. [http://ar.iiarjournals.org/content/30/7/3031.long link to original article] '''contains dosing details in abstract''' [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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21502556 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. [https://www.jto.org/article/S1556-0864(15)32944-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22895140 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. [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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25732163 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. [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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27061082 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. [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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27566413 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. [https://doi.org/10.1200/JCO.2016.67.6601 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27458307 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. [https://doi.org/10.1200/JCO.2016.69.4844 link to original article] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28240967 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. [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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29529858 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. [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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32468956/ PubMed] NCT03066778
 
−
==Cisplatin & Etoposide (EP) & Bevacizumab {{#subobject:f451bd|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:3f85eb|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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.2010.29.3423 Spigel et al. 2011 (SALUTE)]
 
−
|2007-2008
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|1. [[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]<br>2. [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<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====
 
−
*[[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
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 
−
'''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21502556 PubMed] 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%"|Years 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)]
 
−
|2017-2018
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|1. [[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]<br> 2. [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><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)]] 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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31590988 PubMed] NCT03043872
 
−
##'''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 & Irinotecan (IC) {{#subobject:277dbd|Regimen=1}}==
 
−
IP: '''<u>I</u>'''rinotecan, '''<u>P</u>'''latinol (Cisplatin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 30/65 {{#subobject:dc3fe1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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 (E-switch-ic)
 
−
|[[#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====
 
−
*[[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
 
−
====Supportive therapy====
 
−
*[[: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 cycles; additional cycles could be given at physician discretion'''
 
−
</div></div><br>
 
−
<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;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/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
 
−
|-
 
−
|[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)]
 
−
|2007-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Amrubicin_.26_Cisplatin_99|Amrubicin & Cisplatin]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
====Supportive therapy====
 
−
*"Hydration and administration of antiemetic drugs."
 
−
'''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%"|Years 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
 
−
|-
 
−
|}
 
−
''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===
 
−
# '''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] '''contains dosing details in manuscript''' [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. -->
 
−
# 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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19349543 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. [https://doi.org/10.1093/annonc/mdq036 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20231298 PubMed] 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] '''contains dosing details in manuscript''' [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}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://pubmed.ncbi.nlm.nih.gov/10439170 Hesketh et al. 1999]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===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; [[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. '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10439170 PubMed]
 
−
==Ifosfamide monotherapy {{#subobject:d04316|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:3276f5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years 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]]
 
−
|-
 
−
| rowspan="2" |[http://www.lungcancerjournal.info/article/S0169-5002%2802)00074-0 Ettinger et al. 2002 (ECOG E1588)]
 
−
|rowspan=2|1988-1990
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[Small_cell_lung_cancer_-_historical#CAV_2|CAV]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
| style="background-color:#1a9851" |Less toxic
 
−
|-
 
−
|2. [[#Teniposide_monotherapy|Teniposide]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*[[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 (Ifex)]]''' (total dose per cycle: 4500 mg/m<sup>2</sup>)
 
−
'''21-day cycle for 4 to 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with CR: another 2 cycles of ifosfamide, then [[#Whole_brain_irradiation_2|prophylactic whole-brain irradiation]] if still in CR
 
−
*Patients with PR: ifosfamide until progression of disease, then salvage [[#Cisplatin_.26_Etoposide_.28EP.29_4|EP]]
 
−
</div></div>
 
−
===References===
 
−
# '''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. [http://www.lungcancerjournal.info/article/S0169-5002%2802)00074-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12234701 PubMed]
 
−
==IVE {{#subobject:d04tr2|Regimen=1}}==
 
−
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%"|Years 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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28975084/ PubMed] NCT00658580
 
−
==Teniposide monotherapy {{#subobject:60479c|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:964e45|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years 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]]
 
−
|-
 
−
| rowspan="2" |[http://www.lungcancerjournal.info/article/S0169-5002%2802)00074-0 Ettinger et al. 2002 (ECOG E1588)]
 
−
|rowspan=2|1988-1990
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[Small_cell_lung_cancer_-_historical#CAV_2|CAV]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
| style="background-color:#1a9851" |Less toxic
 
−
|-
 
−
|2. [[#Ifosfamide_monotherapy|Ifosfamide]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with CR after 4 to 6 cycles: another 2 cycles of teniposide
 
−
*Patients with CR after 6 to 8 cycles: [[#Whole_brain_irradiation_2|prophylactic whole-brain irradiation]]
 
−
*Patients with PR: teniposide until progression of disease, then salvage [[#Cisplatin_.26_Etoposide_.28EP.29_4|EP]]
 
−
</div></div>
 
−
===References===
 
−
# '''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. [http://www.lungcancerjournal.info/article/S0169-5002%2802)00074-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12234701 PubMed]
 
−
=Extensive stage, consolidation after first-line therapy=
 
−
==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%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.lungcancerjournal.info/article/S0169-5002%2802)00074-0 Ettinger et al. 2002 (ECOG E1588)]
 
−
|1988-1990
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa071780 Slotman et al. 2007 (EORTC 22993)]
 
−
|2001-2006
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Small_cell_lung_cancer_-_null_regimens#Observation_2|Observation]]
 
−
| style="background-color:#1a9850" |Superior OS<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|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: 20 Gy in 5 or 8 fractions, 24 Gy in 12 fractions, 25 Gy in 10 fractions, or 30 Gy in 10 or 12 fractions
 
−
'''1- to 3-week course'''
 
−
</div></div>
 
−
===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. [http://www.lungcancerjournal.info/article/S0169-5002%2802)00074-0 link to original article] '''contains dosing details in manuscript''' [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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17699816 PubMed] NCT00016211
 
−
=Extensive stage, maintenance after first-line therapy=
 
−
==Bevacizumab monotherapy {{#subobject:e2a180|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:60322b|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.29.3423 Spigel et al. 2011 (SALUTE)]
 
−
| style="background-color:#91cf61" |Non-randomized portion 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
 
−
'''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21502556 PubMed] 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%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mds213 Reck et al. 2012 (CA184-041)]
 
−
|2008-2009
 
−
| style="background-color:#91cf61" |Non-randomized portion 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===
 
−
# '''CA184-041:''' 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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22858559 PubMed] 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;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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
 
−
|-
 
−
|}
 
−
<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)]] 150 mg PO once on day 1, then 37.5 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25732163 PubMed] NCT00453154
 
−
=Relapsed or refractory disease=
 
−
==Amrubicin monotherapy {{#subobject:35370b|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:514e41|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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.2013.54.5392 von Pawel et al. 2014 (ACT-1)]
 
−
|2007-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#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|Nivolumab]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Amrubicin (Calsed)]] 40 mg/m<sup>2</sup> 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'''
 
−
</div></div>
 
−
===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. -->
 
−
# '''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25385727 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. [https://doi.org/10.1016/j.annonc.2021.01.071 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33539946/ PubMed] NCT02481830
 
−
==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%"|Years 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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24736081 PubMed] NCT00984542
 
−
==Carboplatin & Etoposide (CE) {{#subobject:dobzc6|Regimen=1}}==
 
−
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%"|Years 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<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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32888454 PubMed] NCT02738346
 
−
==Cisplatin & Etoposide (EP) {{#subobject:eb644a|Regimen=1}}==
 
−
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%"|Years 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)]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Stub#BTOC|BTOC]]
 
−
| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 
−
|-
 
−
|[http://www.lungcancerjournal.info/article/S0169-5002%2802)00074-0 Ettinger et al. 2002 (ECOG E1588)]
 
−
|1988-1990
 
−
| style="background-color:#91cf61" |Non-randomized portion 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====
 
−
*[[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
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===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. [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. [http://www.lungcancerjournal.info/article/S0169-5002%2802)00074-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12234701 PubMed]
 
−
==Cisplatin, Etoposide, Irinotecan {{#subobject:11d584|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:e7a275|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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)]
 
−
|2007-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Topotecan_monotherapy|Topotecan]]
 
−
| style="background-color:#1a9850" |Superior OS<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 once per day on days 1 & 8
 
−
*[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
*[[Irinotecan (Camptosar)]] 90 mg/m<sup>2</sup> IV 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===
 
−
# '''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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27312053 PubMed] UMIN000000828
 
−
==Docetaxel monotherapy {{#subobject:5918ce|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a6b72f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/0959-8049(94)90455-3 Smyth et al. 1994]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7654428 PubMed]
 
−
==Etoposide monotherapy {{#subobject:4ae4d4|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:4970d7|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://pubmed.ncbi.nlm.nih.gov/2154857 Einhorn et al. 1990]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1990.8.10.1613 Johnson et al. 1990]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: Oral etoposide to be taken on an empty stomach.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> PO once per day
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===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''' [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. [https://doi.org/10.1200/jco.1990.8.10.1613 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2170589 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;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.lungcancerjournal.info/article/S0169-5002%2811)00386-2 Jacot et al. 2012]
 
−
|1992-2010
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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===
 
−
# 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. [http://www.lungcancerjournal.info/article/S0169-5002%2811)00386-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21831476 PubMed]
 
−
==Gemcitabine monotherapy {{#subobject:9a9c65|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 5 cycles {{#subobject:5efd8c|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1023/a:1011104509759 van der Lee et al. 2001]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<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
 
−
'''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" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2003.09.130 Masters et al. 2003 (ECOG E1597)]
 
−
| 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====
 
−
*[[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 cycles'''
 
−
</div></div>
 
−
===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. [https://doi.org/10.1023/a:1011104509759 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11398892 PubMed]
 
−
# '''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12697880 PubMed]
 
−
==Ifosfamide monotherapy {{#subobject:a1f3a|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:d82a3f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/0277-5379(88)90242-8 Cantwell et al. 1988]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Ifosfamide (Ifex)]] 5000 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] 5000 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===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. [https://doi.org/10.1016/0277-5379(88)90242-8 link to original article] '''contains dosing details in abstract''' [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. [http://www.karger.com/Article/FullText/73358 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14586147 PubMed]
 
−
==Ifosfamide & Paclitaxel {{#subobject:6540a2|Regimen=1}}==
 
−
PI: '''<u>P</u>'''aclitaxel, '''<u>I</u>'''fosfamide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:8e22a|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.lungcancerjournal.info/article/S0169-5002%2807)00325-X Park et al. 2007a]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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====
 
−
*[[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. [http://www.lungcancerjournal.info/article/S0169-5002%2807)00325-X link to original article] '''contains dosing details in manuscript''' [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" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1992.10.8.1225 Masuda et al. 1992]
 
−
| style="background-color:#ffffbe" |Phase 2, <20 pts
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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.
 
−
'''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%"|Years 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/10.1016/j.lungcan.2022.03.003 Edelman et al. 2022 (DISTINCT)]
 
−
|rowspan=2|2017-NR in abstract
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Irinotecan_.26_Dinutuximab_99|Irinotecan & Dinutuximab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|2. [[#Topotecan_monotherapy|Topotecan]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Irinotecan (Camptosar)]] 350 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===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. [https://doi.org/10.1200/jco.1992.10.8.1225 link to original article] '''contains dosing details in manuscript''' [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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/35278766/ PubMed] NCT03098030
 
−
==Lurbinectedin monotherapy {{#subobject:7167f3|Regimen=1}}==
 
−
<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%"|Years 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)]
 
−
|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====
 
−
*[[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] '''contains dosing details in manuscript''' Epub 2020 Mar 27. [https://pubmed.ncbi.nlm.nih.gov/32224306/ PubMed] NCT02454972
 
−
==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" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151229/ Smit et al. 1998]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> 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 (Taxol)]]
 
−
*[[Clemastine (Tavist)]] 2 mg IV push once on day 1; 30 minutes prior to [[Paclitaxel (Taxol)]]
 
−
*One of the following H2 blockers:
 
−
**[[Cimetidine (Tagamet)]] 300 mg IV push once on day 1; 30 minutes prior to [[Paclitaxel (Taxol)]]
 
−
**[[Ranitidine (Zantac)]] 50 mg IV push once on day 1; 30 minutes prior to [[Paclitaxel (Taxol)]]
 
−
'''21-day cycle for up to 5 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, weekly paclitaxel {{#subobject:658a5f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://ar.iiarjournals.org/content/26/1B/777.long Yamamoto et al. 2006]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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====
 
−
*[[Dexamethasone (Decadron)]] 20 mg IV once per day on days 1, 8, 15, 22, 29, 36; 30 minutes prior to [[Paclitaxel (Taxol)]]
 
−
*[[Ranitidine (Zantac)]] 50 mg IV once per day on days 1, 8, 15, 22, 29, 36; 30 minutes prior to [[Paclitaxel (Taxol)]]
 
−
*[[Diphenhydramine (Benadryl)]] 50 mg IV once per day on days 1, 8, 15, 22, 29, 36; 30 minutes prior to [[Paclitaxel (Taxol)]]
 
−
*If ANC less than 1000/uL 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 greater than or equal to 10 x 10<sup>9</sup>/L, except on days that paclitaxel is given
 
−
'''8-week cycles'''
 
−
</div></div>
 
−
===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://doi.org/10.1038/bjc.1998.54 link to original article] '''contains dosing details in manuscript''' [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. [http://ar.iiarjournals.org/content/26/1B/777.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16739353 PubMed]
 
−
==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}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://clincancerres.aacrjournals.org/content/18/4/1138.long Pietanza et al. 2012]
 
−
|2008-2010
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Temozolomide (Temodar)]] 75 mg/m<sup>2</sup> PO once per day on days 1 to 21, with no food 2 hours before or 1 hour after temozolomide
 
−
====Supportive therapy====
 
−
*[[Ondansetron (Zofran)]] 8 mg PO once per day on days 1 to 21, prior to [[Temozolomide (Temodar)]] prn nausea
 
−
*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" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497567/ Zauderer et al. 2014 (MSKCC 08-065)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> 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 (Temodar)]]
 
−
'''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. [http://clincancerres.aacrjournals.org/content/18/4/1138.long link to original article] '''contains dosing details in manuscript''' [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://www.lungcancerjournal.info/article/S0169-5002(14)00349-3 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25194640 PubMed] NCT00740636
 
−
==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}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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)]
 
−
|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====
 
−
*[[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%"|Years 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]
 
−
|NR
 
−
| 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 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|Nivolumab]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1016/j.jtho.2021.02.009 Blackhall et al. 2021 (TAHOE)]
 
−
|2017-2018
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Rovalpituzumab_tesirine_monotherapy_77|Rovalpituzumab tesirine]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1016/j.lungcan.2022.03.003 Edelman et al. 2022 (DISTINCT)]
 
−
|rowspan=2|2017-NR in abstract
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Irinotecan_.26_Dinutuximab_99|Irinotecan & Dinutuximab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|2. [[#Irinotecan_monotherapy|Irinotecan]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Topotecan (Hycamtin)]] 1.5 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*(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."
 
−
'''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.
 
−
</div></div><br>
 
−
<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;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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.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
 
−
|-
 
−
|[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 (C)
 
−
|[[#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)]
 
−
|2015-2017
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Small_cell_lung_cancer_-_historical#Nivolumab_monotherapy|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====
 
−
*[[Topotecan (Hycamtin)]] 2.3 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''21-day cycle for 4 or more cycles (see note)'''
 
−
</div></div>
 
−
===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. [https://doi.org/10.1200/jco.1999.17.2.658 link to original article] '''contains dosing details in manuscript''' [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. -->
 
−
# '''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17135646 PubMed] NCT00276276
 
−
<!-- 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. [https://doi.org/10.1200/jco.2006.08.3998 link to original article] '''contains dosing details in manuscript''' [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. -->
 
−
# '''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25385727 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. [https://doi.org/10.1016/S1470-2045(16)30104-8 link to original article] '''contains dosing details in abstract''' [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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32888454 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. [https://doi.org/10.1016/j.annonc.2021.01.071 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33539946/ 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. [https://doi.org/10.1016/j.jtho.2021.02.009 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33607312/ 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. [https://doi.org/10.1016/j.lungcan.2022.03.003 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/35278766/ PubMed] NCT03098030
 
−
==Vinorelbine monotherapy {{#subobject:4177e0|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 25 mg/m<sup>2</sup> {{#subobject:be1346|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.karger.com/Article/Abstract/227555 Furuse et al. 1996a]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<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
 
−
'''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" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ejcancer.com/article/0959-8049(93)90112-S/pdf Jassem et al. 1993]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# 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://www.ejcancer.com/article/0959-8049(93)90112-S/pdf link to original article] '''contains dosing details in abstract''' [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://www.karger.com/Article/Abstract/227555 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8604245 PubMed]
 
−
[[Category:Small cell lung cancer regimens]]
 
−
[[Category:Disease-specific pages]]
 
−
[[Category:Lung cancers]]
 

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