Difference between revisions of "Small cell lung cancer - historical"
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− | The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only | + | <span id="BackToTop"></span> |
− | + | <div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px"> | |
+ | [[#top|Back to Top]] | ||
+ | </div> | ||
+ | The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the [[Small_cell_lung_cancer|main SCLC page]] for current regimens. | ||
{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
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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> | <div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div> | ||
|} | |} | ||
− | |||
{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
− | |||
=Limited stage, induction= | =Limited stage, induction= | ||
− | ==CAV {{#subobject: | + | ==CAV {{#subobject:10ggc3|Regimen=1}}== |
− | |||
− | |||
− | |||
− | |||
CAV: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine | CAV: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:4bb088|Variant=1}}=== | ===Regimen {{#subobject:4bb088|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | + | !style="width: 20%"|Comparator | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
|- | |- | ||
|[https://doi.org/10.1200/JCO.1993.11.7.1223 Johnson et al. 1993] | |[https://doi.org/10.1200/JCO.1993.11.7.1223 Johnson et al. 1993] | ||
− | | style="background-color:# | + | |1982-1985 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#CAV_.26_RT|CAV & RT]] | ||
+ | | style="background-color:#fee08b" |Might have inferior OS24 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> (maximum dose of 2000 mg) IV once on day 1 |
− | *[[Doxorubicin (Adriamycin)]] | + | *[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> (maximum dose of 100 mg) IV once on day 1 |
− | *[[Vincristine (Oncovin)]] | + | *[[Vincristine (Oncovin)]] 1 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 |
− | + | '''21-day cycle for 6 cycles''' | |
− | '''21-day cycle for 6 cycles''' | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | + | # Johnson DH, Bass D, Einhorn LH, Crawford J, Perez CA, Bartolucci A, Omura GA, Greco FA; Southeastern Cancer Study Group. Combination chemotherapy with or without thoracic radiotherapy in limited-stage small-cell lung cancer: a randomized trial of the Southeastern Cancer Study Group. J Clin Oncol. 1993 Jul;11(7):1223-9. [https://doi.org/10.1200/JCO.1993.11.7.1223 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8391064/ PubMed] | |
− | # Johnson DH, Bass D, Einhorn LH, Crawford J, Perez CA, Bartolucci A, Omura GA, Greco FA; Southeastern Cancer Study Group. Combination chemotherapy with or without thoracic radiotherapy in limited-stage small-cell lung cancer: a randomized trial of the Southeastern Cancer Study Group. J Clin Oncol. 1993 Jul;11(7):1223-9. [https://doi.org/10.1200/JCO.1993.11.7.1223 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8391064 PubMed] | ||
− | == | + | ==CAV/PE {{#subobject:106cc3|Regimen=1}}== |
− | {| class="wikitable" style=" | + | CAV/PE: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine alternating with '''<u>P</u>'''latinol (Cisplatin) & '''<u>E</u>'''toposide |
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen {{#subobject:4bb088|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.1987.5.9.1401 Feld et al. 1987] | ||
+ | |1981-1984 | ||
+ | | style="background-color:#1a9851" |Randomized (E-switch-ic) | ||
+ | |[[#CAV-PE_999|CAV-PE]] | ||
+ | | style="background-color:#ffffbf" |Did not meet efficacy endpoints | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, CAV portion (cycles 1, 3, 5)==== | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Vincristine (Oncovin)]] 2 mg IV once on day 1 | ||
+ | ====Chemotherapy, PE portion (cycles 2, 4, 6)==== | ||
+ | *[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 40 to 60 minutes once on day 1 | ||
+ | '''21-day cycle for 6 cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Feld R, Evans WK, Coy P, Hodson I, MacDonald AS, Osoba D, Payne D, Shelley W, Pater JL. Canadian multicenter randomized trial comparing sequential and alternating administration of two non-cross-resistant chemotherapy combinations in patients with limited small-cell carcinoma of the lung. J Clin Oncol. 1987 Sep;5(9):1401-9. [https://doi.org/10.1200/JCO.1987.5.9.1401 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/3040923/ PubMed] | ||
+ | ==MACC {{#subobject:219cc3|Regimen=1}}== | ||
MACC: '''<u>M</u>'''ethotrexate, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>C</u>'''CNU (Lomustine) | MACC: '''<u>M</u>'''ethotrexate, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>C</u>'''CNU (Lomustine) | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:4ee088|Variant=1}}=== | ===Regimen {{#subobject:4ee088|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 55: | Line 82: | ||
|[https://doi.org/10.1200/JCO.1985.3.7.969 Maurer et al. 1985 (CALGB 7781)] | |[https://doi.org/10.1200/JCO.1985.3.7.969 Maurer et al. 1985 (CALGB 7781)] | ||
|1977-1981 | |1977-1981 | ||
− | | style="background-color:#1a9851" |Phase 3 (E) | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
− | |CCV/AV | + | |[[#CCV.2FAV_888|CCV/AV]] |
| style="background-color:#ffffbf" |Did not meet endpoint of OS | | style="background-color:#ffffbf" |Did not meet endpoint of OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Methotrexate (MTX)]] | + | *[[Methotrexate (MTX)]] 30 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Doxorubicin (Adriamycin)]] | + | *[[Doxorubicin (Adriamycin)]] 35 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Lomustine (CCNU)]] | + | *[[Lomustine (CCNU)]] 30 mg/m<sup>2</sup> PO once on day 1 |
− | + | '''21-day cycle for 2 cycles''' | |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[#Radiation_therapy|RT]] consolidation | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''CALGB 7781:''' Maurer LH, Pajak T, Eaton W, Comis R, Chahinian P, Faulkner C, Silberfarb PM, Henderson E, Rege VB, Baldwin PE, Weiss R, Rafla S, Prager D, Carey R, Perry M, Choi NC. Combined modality therapy with radiotherapy, chemotherapy, and immunotherapy in limited small-cell carcinoma of the lung: a Phase III Cancer and Leukemia Group B Study. J Clin Oncol. 1985 Jul;3(7):969-76. [https://doi.org/10.1200/JCO.1985.3.7.969 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2991478 PubMed] | + | # '''CALGB 7781:''' Maurer LH, Pajak T, Eaton W, Comis R, Chahinian P, Faulkner C, Silberfarb PM, Henderson E, Rege VB, Baldwin PE, Weiss R, Rafla S, Prager D, Carey R, Perry M, Choi NC. Combined modality therapy with radiotherapy, chemotherapy, and immunotherapy in limited small-cell carcinoma of the lung: a Phase III Cancer and Leukemia Group B Study. J Clin Oncol. 1985 Jul;3(7):969-76. [https://doi.org/10.1200/JCO.1985.3.7.969 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2991478/ PubMed] |
− | ==VMV | + | ==VMV/VAC {{#subobject:139cc3|Regimen=1}}== |
− | + | VMV/VAC: '''<u>V</u>'''incristine, '''<u>M</u>'''ethotrexate, '''<u>V</u>'''P-16 (Etoposide) alternating with '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide | |
− | + | <div class="toccolours" style="background-color:#ee6b6e"> | |
− | |||
− | |||
− | VMV | ||
===Regimen {{#subobject:4cc088|Variant=1}}=== | ===Regimen {{#subobject:4cc088|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1200/JCO.1987.5.4.592 Kies et al. 1987] | |[https://doi.org/10.1200/JCO.1987.5.4.592 Kies et al. 1987] | ||
− | | style="background-color:#91cf61" |Non-randomized | + | |1979-1982 |
+ | | style="background-color:#91cf61" |Non-randomized part of RCT | ||
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Vincristine (Oncovin)]] | + | ====Chemotherapy, VMV portion (cycles 1 & 3)==== |
− | *[[Methotrexate (MTX)]] | + | *[[Vincristine (Oncovin)]] as follows: |
− | *[[Etoposide (Vepesid)]] | + | **Cycle 1: 2 mg IV once per day on days 1, 8, 15 |
− | *[[Doxorubicin (Adriamycin)]] | + | *[[Methotrexate (MTX)]] 60 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 5 |
− | + | ====Chemotherapy, VAC portion (cycles 2 & 4)==== | |
+ | *[[Vincristine (Oncovin)]] as follows: | ||
+ | **Cycle 2: 2 mg IV once per day on days 1, 8, 15 | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | ||
+ | '''21-day cycle for 4 cycles (VMV x 2; VAC x 2)''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Kies MS, Mira JG, Crowley JJ, Chen TT, Pazdur R, Grozea PN, Rivkin SE, Coltman CA Jr, Ward JH, Livingston RB; [[Study_Groups#SWOG|SWOG]]. Multimodal therapy for limited small-cell lung cancer: a randomized study of induction combination chemotherapy with or without thoracic radiation in complete responders; and with wide-field versus reduced-field radiation in partial responders: a Southwest Oncology Group study. J Clin Oncol. 1987 Apr;5(4):592-600. [https://doi.org/10.1200/JCO.1987.5.4.592 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3031226 PubMed] | + | # Kies MS, Mira JG, Crowley JJ, Chen TT, Pazdur R, Grozea PN, Rivkin SE, Coltman CA Jr, Ward JH, Livingston RB; [[Study_Groups#SWOG|SWOG]]. Multimodal therapy for limited small-cell lung cancer: a randomized study of induction combination chemotherapy with or without thoracic radiation in complete responders; and with wide-field versus reduced-field radiation in partial responders: a Southwest Oncology Group study. J Clin Oncol. 1987 Apr;5(4):592-600. [https://doi.org/10.1200/JCO.1987.5.4.592 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/3031226/ PubMed] |
=Limited stage, definitive chemoradiotherapy= | =Limited stage, definitive chemoradiotherapy= | ||
− | == | + | ==CCDE & RT {{#subobject:189bcc|Regimen=1}}== |
− | + | CCDE/RT: '''<u>C</u>'''yclophosphamide, '''<u>C</u>'''isplatin, '''<u>D</u>'''oxorubicin, '''<u>E</u>'''toposide, alternating with '''<u>R</u>'''adiation '''<u>T</u>'''herapy | |
− | + | <div class="toccolours" style="background-color:#ee6b6e"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:dd9b40|Variant=1}}=== | ===Regimen {{#subobject:dd9b40|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM199312163292504 Arriagada et al. 1993] |
|1988-1991 | |1988-1991 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
− | |[# | + | |[[#CCDE.2FRT|CCDE/RT]]; lower-dose |
| style="background-color:#91cf60" |Seems to have superior OS | | style="background-color:#91cf60" |Seems to have superior OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] as follows: |
− | *[[Cisplatin (Platinol)]] | + | **Cycle 1: 300 mg/m<sup>2</sup> IV once per day on days 2 to 5 |
− | *[[Doxorubicin (Adriamycin)]] | + | **Cycles 2 to 6: 225 mg/m<sup>2</sup> IV once per day on days 2 to 5 |
− | *[[Etoposide (Vepesid)]] | + | *[[Cisplatin (Platinol)]] as follows: |
+ | **Cycle 1: 100 mg/m<sup>2</sup> IV once on day 2 | ||
+ | **Cycles 2 to 6: 80 mg/m<sup>2</sup> IV once on day 2 | ||
+ | *[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
*[[External beam radiotherapy]] | *[[External beam radiotherapy]] | ||
− | + | '''6 cycles, alternating with radiation after the 2nd, 3rd, and 4th cycle''' | |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Arriagada R, Le Chevalier T, Pignon JP, Rivière A, Monnet I, Chomy P, Tuchais C, Tarayre M, Ruffié P. Initial chemotherapeutic doses and survival in patients with limited small-cell lung cancer. N Engl J Med. 1993 Dec 16;329(25):1848-52. [https:// | + | # Arriagada R, Le Chevalier T, Pignon JP, Rivière A, Monnet I, Chomy P, Tuchais C, Tarayre M, Ruffié P. Initial chemotherapeutic doses and survival in patients with limited small-cell lung cancer. N Engl J Med. 1993 Dec 16;329(25):1848-52. [https://doi.org/10.1056/NEJM199312163292504 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8247036/ PubMed] |
==CAV & RT {{#subobject:a37yf8|Regimen=1}}== | ==CAV & RT {{#subobject:a37yf8|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CAV & RT: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | CAV & RT: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:8801k9|Variant=1}}=== | ===Regimen {{#subobject:8801k9|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.1984.2.11.1200 Perez et al. 1984] | ||
+ | |1978-1982 | ||
+ | | style="background-color:#1a9851" |Randomized (E-esc) | ||
+ | |[[#CAV|CAV]] | ||
+ | | style="background-color:#d9ef8b" |Might have superior DFS<sup>1</sup> | ||
|- | |- | ||
|[https://doi.org/10.1200/JCO.1990.8.1.33 Jett et al. 1990] | |[https://doi.org/10.1200/JCO.1990.8.1.33 Jett et al. 1990] | ||
|1979-1986 | |1979-1986 | ||
| style="background-color:#1a9851" |Randomized (C) | | style="background-color:#1a9851" |Randomized (C) | ||
− | |CAVE & RT | + | |[[#CAVE_.26_RT_999|CAVE & RT]] |
| style="background-color:#ffffbf" |Did not meet endpoint of OS | | style="background-color:#ffffbf" |Did not meet endpoint of OS | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.1993.11.7.1223 Johnson et al. 1993] | ||
+ | |1982-1985 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |[[#CAV|CAV]] | ||
+ | | style="background-color:#d9ef8b" |Might have superior OS24<br>OS24: 33% vs 23.5% | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>It is not clear from the manuscript what the primary endpont of the study was.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Doxorubicin (Adriamycin)]] | + | *[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Vincristine (Oncovin)]] | + | *[[Vincristine (Oncovin)]] 1 mg/m<sup>2</sup> IV once on day 1 |
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]] | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] as follows: |
− | + | **Cycle 1: 3000 cGy in 300 cGy fractions on days 1 to 5, 8 to 12 | |
+ | **Cycle 3: 1500 cGy in 300 cGy fractions on days 1 to 5 | ||
+ | '''21-day cycle for 6 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Jett JR, Everson L, Therneau TM, Krook JE, Dalton RJ, Marschke RF Jr, Veeder MH, Brunk SF, Mailliard JA, Twito DI, Earle JD, Anderson RT; North Central Cancer Treatment Group. Treatment of limited-stage small-cell lung cancer with cyclophosphamide, doxorubicin, and vincristine with or without etoposide: a randomized trial of the North Central Cancer Treatment Group. J Clin Oncol. 1990 Jan;8(1):33-8. [https://doi.org/10.1200/JCO.1990.8.1.33 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2153193 PubMed] | + | # Perez CA, Einhorn L, Oldham RK, Greco FA, Cohen HJ, Silberman H, Krauss S, Hornback N, Comas F, Omura G, Salter M, Keller JW, McLaren J, Kellermeyer R, Storaasli J, Birch R, Dandy M; Southeastern Cancer Study Group. Randomized trial of radiotherapy to the thorax in limited small-cell carcinoma of the lung treated with multiagent chemotherapy and elective brain irradiation: a preliminary report. J Clin Oncol. 1984 Nov;2(11):1200-8. [https://doi.org/10.1200/jco.1984.2.11.1200 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6092555/ PubMed] |
+ | # Jett JR, Everson L, Therneau TM, Krook JE, Dalton RJ, Marschke RF Jr, Veeder MH, Brunk SF, Mailliard JA, Twito DI, Earle JD, Anderson RT; North Central Cancer Treatment Group. Treatment of limited-stage small-cell lung cancer with cyclophosphamide, doxorubicin, and vincristine with or without etoposide: a randomized trial of the North Central Cancer Treatment Group. J Clin Oncol. 1990 Jan;8(1):33-8. [https://doi.org/10.1200/JCO.1990.8.1.33 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2153193/ PubMed] | ||
+ | # Johnson DH, Bass D, Einhorn LH, Crawford J, Perez CA, Bartolucci A, Omura GA, Greco FA; Southeastern Cancer Study Group. Combination chemotherapy with or without thoracic radiotherapy in limited-stage small-cell lung cancer: a randomized trial of the Southeastern Cancer Study Group. J Clin Oncol. 1993 Jul;11(7):1223-9. [https://doi.org/10.1200/JCO.1993.11.7.1223 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8391064/ PubMed] | ||
==CEV & RT {{#subobject:a3e998|Regimen=1}}== | ==CEV & RT {{#subobject:a3e998|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CEV & RT: '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin, '''<u>V</u>'''incristine, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | CEV & RT: '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin, '''<u>V</u>'''incristine, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:88c1d9|Variant=1}}=== | ===Regimen {{#subobject:88c1d9|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |rowspan=2|[https:// | + | |rowspan=2|[https://doi.org/10.1056/NEJM198704093161504 Perry et al. 1987 (CALGB 8083)] |
|rowspan=2|1981-1984 | |rowspan=2|1981-1984 | ||
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc) | |rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc) | ||
− | |1. CEV | + | |1. [[#CEV_.28Cyclophosphamide.2FEpirubicin.29|CEV]] |
| style="background-color:#1a9850" |Superior OS | | style="background-color:#1a9850" |Superior OS | ||
|- | |- | ||
− | |2. CEV, then RT | + | |2. [[#CEV_.28Cyclophosphamide.2FEpirubicin.29|CEV]], then [[#Radiation_therapy_888|RT]] |
| style="background-color:#d3d3d3" |Not reported | | style="background-color:#d3d3d3" |Not reported | ||
|- | |- | ||
Line 189: | Line 242: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] as follows: |
− | *[[Epirubicin (Ellence)]] | + | **Cycles 1 to 3, 5, 6: 1000 mg/m<sup>2<sup> IV once on day 1 |
− | *[[Vincristine (Oncovin)]] | + | *[[Epirubicin (Ellence)]] as follows: |
+ | **Cycles 1 to 3, 5, 6: 50 mg/m<sup>2<sup> IV once on day 1 | ||
+ | *[[Vincristine (Oncovin)]] as follows: | ||
+ | **Cycles 1 to 3, 5, 6: 2 mg IV once on day 1 | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | * | + | *[[External_beam_radiotherapy|radiation therapy]] as follows: |
+ | **Cycle 4: 280 cGy once per day on days 1 to 5, 8 to 12, 15 to 19 (4200 cGy total) | ||
+ | '''21-day cycle for up to 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | * | + | *CALGB 8083: Prophylactic [[Small_cell_lung_cancer#Whole_brain_irradiation|cranial irradiation]] |
+ | *Sundstrøm et al. 2002, patients with CR: Prophylactic [[Small_cell_lung_cancer#Whole_brain_irradiation|cranial irradiation]] | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''CALGB 8083:''' Perry MC, Eaton WL, Propert KJ, Ware JH, Zimmer B, Chahinian AP, Skarin A, Carey RW, Kreisman H, Faulkner C, Comis R, Green MR. Chemotherapy with or without radiation therapy in limited small-cell carcinoma of the lung. N Engl J Med. 1987 Apr 9;316(15):912-8. [https:// | + | # '''CALGB 8083:''' Perry MC, Eaton WL, Propert KJ, Ware JH, Zimmer B, Chahinian AP, Skarin A, Carey RW, Kreisman H, Faulkner C, Comis R, Green MR. Chemotherapy with or without radiation therapy in limited small-cell carcinoma of the lung. N Engl J Med. 1987 Apr 9;316(15):912-8. [https://doi.org/10.1056/NEJM198704093161504 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3029592/ 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] ''' | + | # Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. [https://doi.org/10.1200/jco.2002.12.111 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12488411/ PubMed] |
− | ==Methotrexate, RT | + | ==Cyclophosphamide, Methotrexate, RT {{#subobject:a4e998|Regimen=1}}== |
− | + | <div class="toccolours" style="background-color:#ee6b6e"> | |
− | + | ===Regimen {{#subobject:78c1d9|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" | |
− | + | !style="width: 33%"|Study | |
− | === | + | !style="width: 33%"|Dates of enrollment |
− | {| class="wikitable" style="width: | + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | ||
− | !style="width: | ||
|- | |- | ||
|[https://doi.org/10.1016/s0140-6736(82)92099-2 Thatcher et al. 1982] | |[https://doi.org/10.1016/s0140-6736(82)92099-2 Thatcher et al. 1982] | ||
− | | style="background-color:#91cf61" |Non-randomized | + | |1978-1981 |
+ | | style="background-color:#91cf61" |Non-randomized part of RCT | ||
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Methotrexate (MTX)]] | + | ====Chemotherapy==== |
+ | *[[Methotrexate (MTX)]] 100 mg/m<sup>2</sup> IV bolus once per day on days 1 & 15 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 1500 mg/m<sup>2</sup> IV bolus once on day 35, then 2500 mg/m<sup>2</sup> IV bolus once on day 56, then 3500 mg/m<sup>2</sup> IV bolus once on day 77 | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy|Radiation therapy]] | + | *[[External_beam_radiotherapy|Radiation therapy]] 3.7500 cGy per fraction on days 16 to 19, 22 to 25 |
− | + | '''11-week course''' | |
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Thatcher N, Barber PV, Hunter RD, Carroll KB, Jegarajah S, Wilkinson PM, Crowther D; Manchester Lung Tumour Group. 11-week course of sequential methotrexate, thoracic irradiation, and moderate-dose cyclophosphamide for "limited"-stage small-cell bronchogenic carcinoma: a study from the Manchester Lung Tumour Group. Lancet. 1982 May 8;1(8280):1040-3. [https://doi.org/10.1016/s0140-6736(82)92099-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6122853 PubMed] | + | # Maurer LH, Tulloh M, Weiss RB, Blom J, Leone L, Glidewell O, Pajak TF; CALGB. A randomized combined modality trial in small cell carcinoma of the lung: comparison of combination chemotherapy-radiation therapy versus cyclophosphamide-radiation therapy effects of maintenance chemotherapy and prophylactiv whole brain irradiation. Cancer. 1980 Jan 1;45(1):30-9. [https://doi.org/10.1002/1097-0142(19800101)45:1%3C30::aid-cncr2820450107%3E3.0.co;2-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6243242/ PubMed] |
+ | # Thatcher N, Barber PV, Hunter RD, Carroll KB, Jegarajah S, Wilkinson PM, Crowther D; Manchester Lung Tumour Group. 11-week course of sequential methotrexate, thoracic irradiation, and moderate-dose cyclophosphamide for "limited"-stage small-cell bronchogenic carcinoma: a study from the Manchester Lung Tumour Group. Lancet. 1982 May 8;1(8280):1040-3. [https://doi.org/10.1016/s0140-6736(82)92099-2 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/6122853/ PubMed] | ||
=Extensive stage, induction= | =Extensive stage, induction= | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
==BACO {{#subobject:8b52ad|Regimen=1}}== | ==BACO {{#subobject:8b52ad|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
BACO: '''<u>B</u>'''leomycin, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine) | BACO: '''<u>B</u>'''leomycin, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine) | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:e3138e|Variant=1}}=== | ===Regimen {{#subobject:e3138e|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1001/jama.1976.03260380019019 Einhorn et al. 1976] |
+ | |1973-06 to 1974-07 | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Bleomycin (Blenoxane)]] | + | *[[Bleomycin (Blenoxane)]] 15 units IV push, '''given second, 6 hours later''' |
− | *[[Doxorubicin (Adriamycin)]] | + | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV push once on day 1, '''given with cyclophosphamide''' |
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV push once on day 1, '''given with doxorubicin''' |
− | *[[Vincristine (Oncovin)]] | + | *[[Vincristine (Oncovin)]] by the following age-based criteria: |
+ | **Younger than 50 years old: 1 mg IV push once on day 2, '''given first''' | ||
+ | **50 years old or older: 0.75 mg IV push once on day 2, '''given first''' | ||
+ | '''21-day cycle for up to 9 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Einhorn LH, Fee WH, Farber MO, Livingston RB, Gottlieb JA. Improved chemotherapy for small-cell undifferentiated lung cancer. JAMA. 1976 Mar 22;235(12):1225-9. [https:// | + | # Einhorn LH, Fee WH, Farber MO, Livingston RB, Gottlieb JA. Improved chemotherapy for small-cell undifferentiated lung cancer. JAMA. 1976 Mar 22;235(12):1225-9. [https://doi.org/10.1001/jama.1976.03260380019019 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/55504/ PubMed] |
− | ==Carboplatin | + | ==Carboplatin & Etoposide (CE) & Pembrolizumab {{#subobject:o9ga26|Regimen=1}}== |
− | |||
− | |||
− | |||
− | |||
CE & Pembrolizumab: '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide, Pembrolizumab | CE & Pembrolizumab: '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide, Pembrolizumab | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:3cn73m|Variant=1}}=== | ===Regimen {{#subobject:3cn73m|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ Rudin et al. 2020 (KEYNOTE-604)] |
− | |2017-2018 | + | |2017-05-15 to 2018-07-30 |
|style="background-color:#1a9851" |Phase 3 (E-esc) | |style="background-color:#1a9851" |Phase 3 (E-esc) | ||
− | | | + | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]] |
− | | style="background-color:# | + | | style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup> (co-primary endpoint)<br>OS24: 22.5% vs 11.2%<br>(HR 0.80, 95% CI 0.64-0.98) |
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>This result did not meet the pre-specified threshold for statistical significance, and was the basis for withdrawal of the FDA indication.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carboplatin (Paraplatin)]] as follows: | *[[Carboplatin (Paraplatin)]] as follows: | ||
Line 322: | Line 344: | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1 | *[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1 | ||
− | |||
'''21-day cycle for up to 35 cycles (2 years)''' | '''21-day cycle for up to 35 cycles (2 years)''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''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] [ | + | # '''KEYNOTE-604:''' Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gümüş M, Kato T, Kalemkerian GP, Luo Y, Ebiana V, Pietanza MC, Kim HR; KEYNOTE-604 Investigators. Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. J Clin Oncol. 2020 Jul 20;38(21):2369-2379. Epub 2020 May 29. [https://doi.org/10.1200/jco.20.00793 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32468956/ PubMed] [https://clinicaltrials.gov/study/NCT03066778 NCT03066778] |
− | |||
==CAV {{#subobject:cbb2ff|Regimen=1}}== | ==CAV {{#subobject:cbb2ff|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CAV: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine | CAV: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine | ||
<br> CAO: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine) | <br> CAO: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine) | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen variant #1, 1000/40/1, capped by BSA {{#subobject:51b1f9|Variant=1}}=== | ===Regimen variant #1, 1000/40/1, capped by BSA {{#subobject:51b1f9|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 17%"|Study | !style="width: 17%"|Study | ||
− | !style="width: 15%"| | + | !style="width: 15%"|Dates of enrollment |
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 17%"|Comparator | !style="width: 17%"|Comparator | ||
Line 344: | Line 362: | ||
|- | |- | ||
|[https://pubmed.ncbi.nlm.nih.gov/3020700 Bunn et al. 1986] | |[https://pubmed.ncbi.nlm.nih.gov/3020700 Bunn et al. 1986] | ||
− | | | + | |Not reported in abstract |
| style="background-color:#1a9851" |Randomized (C) | | style="background-color:#1a9851" |Randomized (C) | ||
|[[#CDE|CDE]] | |[[#CDE|CDE]] | ||
Line 359: | Line 377: | ||
|} | |} | ||
''Note: the original manuscript with dosing for Bunn et al. 1986 is not available for review.'' | ''Note: the original manuscript with dosing for Bunn et al. 1986 is not available for review.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> (maximum dose of 2000 mg) IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> (maximum dose of 2000 mg) IV once on day 1 | ||
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> (maximum dose of 80 mg) IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> (maximum dose of 80 mg) IV once on day 1 | ||
*[[Vincristine (Oncovin)]] 1 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 | *[[Vincristine (Oncovin)]] 1 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 | ||
− | |||
'''21-day cycle for 6 cycles''' | '''21-day cycle for 6 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen variant #2, 1000/50/1.4, uncapped vincristine {{#subobject:d8e9d5|Variant=1}}=== | ===Regimen variant #2, 1000/50/1.4, uncapped vincristine {{#subobject:d8e9d5|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 17%"|Study | !style="width: 17%"|Study | ||
− | !style="width: 15%"| | + | !style="width: 15%"|Dates of enrollment |
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 17%"|Comparator | !style="width: 17%"|Comparator | ||
Line 375: | Line 394: | ||
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | |[https://doi.org/10. | + | | rowspan="2" |[https://doi.org/10.1016/s0169-5002(02)00074-0 Ettinger et al. 2002 (ECOG E1588)] |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
|rowspan=2|1988-1990 | |rowspan=2|1988-1990 | ||
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C) | | rowspan="2" style="background-color:#1a9851" |Phase 3 (C) | ||
Line 393: | Line 405: | ||
| style="background-color:#d73027" |More toxic | | style="background-color:#d73027" |More toxic | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(96)02005-3 Girling 1996] |
|1992-1995 | |1992-1995 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | | | + | |[[#Etoposide_monotherapy|Etoposide]]; oral |
| style="background-color:#91cf60" |Seems to have superior OS | | style="background-color:#91cf60" |Seems to have superior OS | ||
| | | | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1 | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''21-day cycle for 4 to 6 cycles''' | '''21-day cycle for 4 to 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *ECOG E1588, CR: [[#CAV_2|CAV]] x 2 (6 to 8 total), then [[#Whole_brain_irradiation_2| | + | *ECOG E1588, CR: [[#CAV_2|CAV]] continuation x 2 (6 to 8 total), then prophylactic [[#Whole_brain_irradiation_2|cranial irradiation]] |
− | *ECOG E1588, PR: [[#CAV_2|CAV]] until progression of disease, then [[#Cisplatin_.26_Etoposide_.28EP.29_3| | + | *ECOG E1588, PR: [[#CAV_2|CAV]] continuation until progression of disease, then salvage [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]] |
− | + | </div></div><br> | |
− | ===Regimen variant #3, 1000/50/2, flat-dose vincristine {{#subobject:3dc31b|Variant=1}}=== | + | <div class="toccolours" style="background-color:#ee6b6e"> |
+ | ===Regimen variant #3, 1000/50/1.4, capped vincristine {{#subobject:cae9d5|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 17%"|Study | ||
+ | !style="width: 15%"|Dates of enrollment | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 17%"|Comparator | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.1990.8.2.230 Ettinger et al. 1990 (ECOG E1582)] | ||
+ | |1982-1985 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#CAV.2FHEM_999|CAV/HEM]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
+ | | style="background-color:#1a9850" |Less toxic | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 | ||
+ | '''21-day cycle for 6 to 8 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #4, 1000/50/2, flat-dose vincristine {{#subobject:3dc31b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 17%"|Study | !style="width: 17%"|Study | ||
− | !style="width: 15%"| | + | !style="width: 15%"|Dates of enrollment |
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 17%"|Comparator | !style="width: 17%"|Comparator | ||
Line 420: | Line 460: | ||
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1001/jama.1977.03270390037022 Holoye et al. 1977] |
|1973-1974 | |1973-1974 | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
Line 427: | Line 467: | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.7326/0003-4819-107-4-451 Evans et al. 1987] |
|1982-1985 | |1982-1985 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
Line 436: | Line 476: | ||
|[https://doi.org/10.1200/JCO.1994.12.1.70 Maksymiuk et al. 1994] | |[https://doi.org/10.1200/JCO.1994.12.1.70 Maksymiuk et al. 1994] | ||
|1987-1990 | |1987-1990 | ||
− | | style="background-color:#91cf61" |Non-randomized | + | | style="background-color:#91cf61" |Non-randomized part of RCT |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
Line 442: | Line 482: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1 | *[[Vincristine (Oncovin)]] 2 mg IV once on day 1 | ||
− | |||
'''21-day cycle for 6 cycles''' | '''21-day cycle for 6 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Holoye PY, Samuels ML, Lanzotti VJ, Smith T, Barkley HT Jr. Combination chemotherapy and radiation therapy for small cell carcinoma. JAMA. 1977 Mar 21;237(12):1221-4. [https:// | + | # Holoye PY, Samuels ML, Lanzotti VJ, Smith T, Barkley HT Jr. Combination chemotherapy and radiation therapy for small cell carcinoma. JAMA. 1977 Mar 21;237(12):1221-4. [https://doi.org/10.1001/jama.1977.03270390037022 link to original article] [https://pubmed.ncbi.nlm.nih.gov/190427/ PubMed] |
− | # Bunn PA Jr, Greco FA, Einhorn L. Cyclophosphamide, doxorubicin, and etoposide as first-line therapy in the treatment of small-cell lung cancer. Semin Oncol. 1986 Sep;13(3 Suppl 3):45-53. [https://pubmed.ncbi.nlm.nih.gov/3020700 PubMed] | + | # Bunn PA Jr, Greco FA, Einhorn L. Cyclophosphamide, doxorubicin, and etoposide as first-line therapy in the treatment of small-cell lung cancer. Semin Oncol. 1986 Sep;13(3 Suppl 3):45-53. [https://pubmed.ncbi.nlm.nih.gov/3020700/ PubMed] |
− | # Evans WK, Feld R, Murray N, Willan A, Coy P, Osoba D, Shepherd FA, Clark DA, Levitt M, MacDonald A, Wilson K, Shelley W, Pater J. Superiority of alternating non-cross-resistant chemotherapy in extensive small cell lung cancer: a multicenter, randomized clinical trial by the National Cancer Institute of Canada. Ann Intern Med. 1987 Oct;107(4):451-8. Erratum in: Ann Intern Med 1988 Mar;108(3):496. [ | + | # Evans WK, Feld R, Murray N, Willan A, Coy P, Osoba D, Shepherd FA, Clark DA, Levitt M, MacDonald A, Wilson K, Shelley W, Pater J. Superiority of alternating non-cross-resistant chemotherapy in extensive small cell lung cancer: a multicenter, randomized clinical trial by the National Cancer Institute of Canada. Ann Intern Med. 1987 Oct;107(4):451-8. Erratum in: Ann Intern Med 1988 Mar;108(3):496. [https://doi.org/10.7326/0003-4819-107-4-451 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2820289/ PubMed] |
− | # Johnson DH, Einhorn LH, Birch R, Vollmer R, Perez C, Krauss S, Omura G, Greco FA; Southeastern Cancer Study Group. A randomized comparison of high-dose versus conventional-dose cyclophosphamide, doxorubicin, and vincristine for extensive-stage small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol. 1987 Nov;5(11):1731-8. [https://doi.org/10.1200/JCO.1987.5.11.1731 link to original article] ''' | + | # Johnson DH, Einhorn LH, Birch R, Vollmer R, Perez C, Krauss S, Omura G, Greco FA; Southeastern Cancer Study Group. A randomized comparison of high-dose versus conventional-dose cyclophosphamide, doxorubicin, and vincristine for extensive-stage small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol. 1987 Nov;5(11):1731-8. [https://doi.org/10.1200/JCO.1987.5.11.1731 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2824707/ PubMed] |
− | # Ettinger DS, Finkelstein DM, Abeloff MD, Ruckdeschel JC, Aisner SC, Eggleston JC; [[Study_Groups#ECOG|ECOG]]. A randomized comparison of standard chemotherapy versus alternating chemotherapy and maintenance versus no maintenance therapy for extensive-stage small-cell lung cancer: a phase III study of the Eastern Cooperative Oncology Group. J Clin Oncol. 1990 Feb;8(2):230-40. [https://doi.org/10.1200/JCO.1990.8.2.230 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2153765 PubMed] | + | # '''ECOG E1582:''' Ettinger DS, Finkelstein DM, Abeloff MD, Ruckdeschel JC, Aisner SC, Eggleston JC; [[Study_Groups#ECOG|ECOG]]. A randomized comparison of standard chemotherapy versus alternating chemotherapy and maintenance versus no maintenance therapy for extensive-stage small-cell lung cancer: a phase III study of the Eastern Cooperative Oncology Group. J Clin Oncol. 1990 Feb;8(2):230-40. [https://doi.org/10.1200/JCO.1990.8.2.230 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2153765/ PubMed] |
− | # Maksymiuk AW, Jett JR, Earle JD, Su JQ, Diegert FA, Mailliard JA, Kardinal CG, Krook JE, Veeder MH, Wiesenfeld M, Tschetter LK, Levitt R; North Central Cancer Treatment Group. Sequencing and schedule effects of cisplatin plus etoposide in small-cell lung cancer: results of a North Central Cancer Treatment Group randomized clinical trial. J Clin Oncol. 1994 Jan;12(1):70-6. [https://doi.org/10.1200/JCO.1994.12.1.70 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8270988 PubMed] | + | # Maksymiuk AW, Jett JR, Earle JD, Su JQ, Diegert FA, Mailliard JA, Kardinal CG, Krook JE, Veeder MH, Wiesenfeld M, Tschetter LK, Levitt R; North Central Cancer Treatment Group. Sequencing and schedule effects of cisplatin plus etoposide in small-cell lung cancer: results of a North Central Cancer Treatment Group randomized clinical trial. J Clin Oncol. 1994 Jan;12(1):70-6. [https://doi.org/10.1200/JCO.1994.12.1.70 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8270988/ PubMed] |
− | # Girling DJ; Medical Research Council Lung Cancer Working Party. Comparison of oral etoposide and standard intravenous multidrug chemotherapy for small-cell lung cancer: a stopped multicentre randomised trial. Lancet. 1996 Aug 31;348(9027):563-6. [https:// | + | # Girling DJ; Medical Research Council Lung Cancer Working Party. Comparison of oral etoposide and standard intravenous multidrug chemotherapy for small-cell lung cancer: a stopped multicentre randomised trial. Lancet. 1996 Aug 31;348(9027):563-6. [https://doi.org/10.1016/S0140-6736(96)02005-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8774567/ 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. [ | + | # '''ECOG E1588:''' Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; [[Study_Groups#ECOG|ECOG]]. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. [https://doi.org/10.1016/s0169-5002(02)00074-0 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12234701/ PubMed] |
==CAV/PE {{#subobject:55aede|Regimen=1}}== | ==CAV/PE {{#subobject:55aede|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CAV/PE: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine alternating with '''<u>P</u>'''latinol (Cisplatin) & '''<u>E</u>'''toposide | CAV/PE: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine alternating with '''<u>P</u>'''latinol (Cisplatin) & '''<u>E</u>'''toposide | ||
− | === | + | <div class="toccolours" style="background-color:#ee6b6e"> |
+ | ===Regimen {{#subobject:2a8dee|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 479: | Line 516: | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.7326/0003-4819-107-4-451 Evans et al. 1987] |
|1982-1985 | |1982-1985 | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
Line 488: | Line 525: | ||
|1985-1989 | |1985-1989 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
− | |1. [[#CAV_2|CAV]]<br> 2. [[Small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29_2|EP]] | + | |1. [[#CAV_2|CAV]]<br>2. [[Small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29_2|EP]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS50% | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS50% | ||
|- | |- | ||
Line 504: | Line 541: | ||
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy, CAV portion==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Cyclophosphamide (Cytoxan)]] | + | ====Chemotherapy, CAV portion (Odd cycles)==== |
− | *[[Doxorubicin (Adriamycin)]] | + | *[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Vincristine (Oncovin)]] | + | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 |
− | + | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1 | |
− | ====Chemotherapy, PE portion==== | + | ====Chemotherapy, PE portion (Even cycles)==== |
− | *[[Cisplatin (Platinol)]] | + | *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Etoposide (Vepesid)]] | + | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> (route not specified) once per day on days 1 to 3 |
− | + | '''21-day cycles''' | |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Evans WK, Feld R, Murray N, Willan A, Coy P, Osoba D, Shepherd FA, Clark DA, Levitt M, MacDonald A, Wilson K, Shelley W, Pater J. Superiority of alternating non-cross-resistant chemotherapy in extensive small cell lung cancer: a multicenter, randomized clinical trial by the National Cancer Institute of Canada. Ann Intern Med. 1987 Oct;107(4):451-8. Erratum in: Ann Intern Med 1988 Mar;108(3):496. [ | + | # Evans WK, Feld R, Murray N, Willan A, Coy P, Osoba D, Shepherd FA, Clark DA, Levitt M, MacDonald A, Wilson K, Shelley W, Pater J. Superiority of alternating non-cross-resistant chemotherapy in extensive small cell lung cancer: a multicenter, randomized clinical trial by the National Cancer Institute of Canada. Ann Intern Med. 1987 Oct;107(4):451-8. Erratum in: Ann Intern Med 1988 Mar;108(3):496. [https://doi.org/10.7326/0003-4819-107-4-451 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2820289/ PubMed] |
− | # '''SWOG S8232:''' Goodman GE, Crowley JJ, Blasko JC, Livingston RB, Beck TM, Demattia MD, Bukowski RM. Treatment of limited small-cell lung cancer with etoposide and cisplatin alternating with vincristine, doxorubicin, and cyclophosphamide versus concurrent etoposide, vincristine, doxorubicin, and cyclophosphamide and chest radiotherapy: a Southwest Oncology Group Study. J Clin Oncol. 1990 Jan;8(1):39-47. [https://doi.org/10.1200/JCO.1990.8.1.39 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2153194 PubMed] | + | # '''SWOG S8232:''' Goodman GE, Crowley JJ, Blasko JC, Livingston RB, Beck TM, Demattia MD, Bukowski RM. Treatment of limited small-cell lung cancer with etoposide and cisplatin alternating with vincristine, doxorubicin, and cyclophosphamide versus concurrent etoposide, vincristine, doxorubicin, and cyclophosphamide and chest radiotherapy: a Southwest Oncology Group Study. J Clin Oncol. 1990 Jan;8(1):39-47. [https://doi.org/10.1200/JCO.1990.8.1.39 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2153194/ 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] [https://pubmed.ncbi.nlm.nih.gov/1310103 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] [https://pubmed.ncbi.nlm.nih.gov/1310103/ PubMed] |
− | # '''JCOG9106:''' Furuse K, Fukuoka M, Nishiwaki Y, Kurita Y, Watanabe K, Noda K, Ariyoshi Y, Tamura T, Saijo N; [[Study_Groups#JCOG|JCOG]]. Phase III study of intensive weekly chemotherapy with recombinant human granulocyte colony-stimulating factor versus standard chemotherapy in extensive-disease small-cell lung cancer. J Clin Oncol. 1998 Jun;16(6):2126-32. [https://doi.org/10.1200/JCO.1998.16.6.2126 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9626212 PubMed] | + | # '''JCOG9106:''' Furuse K, Fukuoka M, Nishiwaki Y, Kurita Y, Watanabe K, Noda K, Ariyoshi Y, Tamura T, Saijo N; [[Study_Groups#JCOG|JCOG]]. Phase III study of intensive weekly chemotherapy with recombinant human granulocyte colony-stimulating factor versus standard chemotherapy in extensive-disease small-cell lung cancer. J Clin Oncol. 1998 Jun;16(6):2126-32. [https://doi.org/10.1200/JCO.1998.16.6.2126 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9626212/ PubMed] |
− | # Murray N, Livingston RB, Shepherd FA, James K, Zee B, Langleben A, Kraut M, Bearden J, Goodwin JW, Grafton C, Turrisi A, Walde D, Croft H, Osoba D, Ottaway J, Gandara D; National Cancer Institute of Canada Clinical Trials Group; [[Study_Groups#SWOG|SWOG]]. Randomized study of CODE versus alternating CAV/EP for extensive-stage small-cell lung cancer: an Intergroup Study of the National Cancer Institute of Canada Clinical Trials Group and the Southwest Oncology Group. J Clin Oncol. 1999 Aug;17(8):2300-8. [https://doi.org/10.1200/JCO.1999.17.8.2300 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10561291 PubMed] | + | # Murray N, Livingston RB, Shepherd FA, James K, Zee B, Langleben A, Kraut M, Bearden J, Goodwin JW, Grafton C, Turrisi A, Walde D, Croft H, Osoba D, Ottaway J, Gandara D; National Cancer Institute of Canada Clinical Trials Group; [[Study_Groups#SWOG|SWOG]]. Randomized study of CODE versus alternating CAV/EP for extensive-stage small-cell lung cancer: an Intergroup Study of the National Cancer Institute of Canada Clinical Trials Group and the Southwest Oncology Group. J Clin Oncol. 1999 Aug;17(8):2300-8. [https://doi.org/10.1200/JCO.1999.17.8.2300 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10561291/ PubMed] |
==CAVE {{#subobject:55aede|Regimen=1}}== | ==CAVE {{#subobject:55aede|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CAVE: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine, '''<u>E</u>'''toposide | CAVE: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine, '''<u>E</u>'''toposide | ||
<br>CAV-E: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine, '''<u>E</u>'''toposide | <br>CAV-E: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine, '''<u>E</u>'''toposide | ||
+ | <br>EVAC: '''<u>E</u>'''toposide, '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:2a8dee|Variant=1}}=== | ===Regimen {{#subobject:2a8dee|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 541: | Line 577: | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1002/%28SICI)1097-0142%2819971215%2980%3A12%3C2222%3A%3AAID-CNCR2%3E3.0.CO%3B2-W Tummarello et al. 1997] |
|1990-1995 | |1990-1995 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |CAV-T | + | |[[#CAV-T_999|CAV-T]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS50% | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS50% | ||
|- | |- | ||
|} | |} | ||
− | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.'' | + | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Doxorubicin (Adriamycin)]] | + | *[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Vincristine (Oncovin)]] | + | *[[Vincristine (Oncovin)]] 1 mg/m<sup>2</sup> IV once per day on days 1 & 8 |
− | *[[Etoposide (Vepesid)]] | + | *[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 1 to 3 |
− | + | '''21-day cycle for 6 cycles''' | |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''SWOG S8232:''' Goodman GE, Crowley JJ, Blasko JC, Livingston RB, Beck TM, Demattia MD, Bukowski RM. Treatment of limited small-cell lung cancer with etoposide and cisplatin alternating with vincristine, doxorubicin, and cyclophosphamide versus concurrent etoposide, vincristine, doxorubicin, and cyclophosphamide and chest radiotherapy: a Southwest Oncology Group Study. J Clin Oncol. 1990 Jan;8(1):39-47. [https://doi.org/10.1200/JCO.1990.8.1.39 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2153194 PubMed] | + | # '''SWOG S8232:''' Goodman GE, Crowley JJ, Blasko JC, Livingston RB, Beck TM, Demattia MD, Bukowski RM. Treatment of limited small-cell lung cancer with etoposide and cisplatin alternating with vincristine, doxorubicin, and cyclophosphamide versus concurrent etoposide, vincristine, doxorubicin, and cyclophosphamide and chest radiotherapy: a Southwest Oncology Group Study. J Clin Oncol. 1990 Jan;8(1):39-47. [https://doi.org/10.1200/JCO.1990.8.1.39 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2153194/ PubMed] |
− | # Tummarello D, Mari D, Graziano F, Isidori P, Cetto G, Pasini F, Santo A, Cellerino R. A randomized, controlled phase III study of cyclophosphamide, doxorubicin, and vincristine with etoposide (CAV-E) or teniposide (CAV-T), followed by recombinant interferon-alpha maintenance therapy or observation, in small cell lung carcinoma patients with complete responses. Cancer. 1997 Dec 15;80(12):2222-9. [https:// | + | # Tummarello D, Mari D, Graziano F, Isidori P, Cetto G, Pasini F, Santo A, Cellerino R. A randomized, controlled phase III study of cyclophosphamide, doxorubicin, and vincristine with etoposide (CAV-E) or teniposide (CAV-T), followed by recombinant interferon-alpha maintenance therapy or observation, in small cell lung carcinoma patients with complete responses. Cancer. 1997 Dec 15;80(12):2222-9. [https://doi.org/10.1002/%28SICI)1097-0142%2819971215%2980%3A12%3C2222%3A%3AAID-CNCR2%3E3.0.CO%3B2-W link to original article] [https://pubmed.ncbi.nlm.nih.gov/9404698/ PubMed] |
==CDE {{#subobject:344f89|Regimen=1}}== | ==CDE {{#subobject:344f89|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | CDE: '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''oxorubicin, '''<u>E</u>'''toposide |
+ | <br>ACE: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide | ||
+ | <br>AVE: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''epesid (Etoposide), '''<u>E</u>'''ndoxan (Cyclophosphamide) | ||
+ | <br>CAE: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>E</u>'''toposide | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #1, 1000/40/480 {{#subobject:cj5ce9|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2004.00.9969 Thatcher et al. 2005 (MRC LU21)] | ||
+ | |1996-03 to 2002-02 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#ICE-V|ICE-V]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | < | + | ====Chemotherapy==== |
− | ===Regimen {{#subobject: | + | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 |
+ | *[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 2 | ||
+ | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 2 & 3, then 240 mg/m<sup>2</sup> PO once on day 3 | ||
+ | '''21-day cycle for 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #2, 1000/45/240 {{#subobject:949381|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1002/1097-0142%2819850701%2956%3A1%3C71%3A%3AAID-CNCR2820560112%3E3.0.CO%3B2-9 Klastersky et al. 1985] | ||
+ | |Not reported | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | | ORR: 66% | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: Used as a comparator arm in older studies. The non-randomized results of Klastersky et al. 1985 established this regimen as a standard control.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | '''21-day cycle for up to 10 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #3, 1000/45/300 {{#subobject:bjgu39|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 575: | Line 659: | ||
|- | |- | ||
|[https://pubmed.ncbi.nlm.nih.gov/3020700 Bunn et al. 1986] | |[https://pubmed.ncbi.nlm.nih.gov/3020700 Bunn et al. 1986] | ||
− | | | + | |Not reported in abstract |
| style="background-color:#1a9851" |Randomized (E-switch-ic) | | style="background-color:#1a9851" |Randomized (E-switch-ic) | ||
|[[#CAV_2|CAV]] | |[[#CAV_2|CAV]] | ||
| style="background-color:#91cf60" |Seems to have superior OS | | style="background-color:#91cf60" |Seems to have superior OS | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1200/JCO.2002.02.069 Ardizzoni et al. 2002 (EORTC 08923)] |
+ | |1994-1999 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#CDE|CDE]]; intensified | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/j.ejca.2007.07.029 de Jong et al. 2007 (CKVO-9802)] | ||
+ | |1999-2005 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Carboplatin_.26_Paclitaxel_.28CP.29_999|CP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | '''21-day cycle for 5 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #4, 1000/45/300, alternate etoposide schedule {{#subobject:be62e9|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/0959-8049(96)00145-1 Postmus et al. 1996] | ||
|1988-1992 | |1988-1992 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |CDE/VIMP | + | |[[#CDE.2FVIMP_999|CDE/VIMP]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |[https://doi.org/10.1200/JCO. | + | |} |
− | | | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Chemotherapy==== | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | ||
+ | '''21-day cycle for 5 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #5, 1000/50/240 {{#subobject:94yb81|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.1993.11.10.1858 Sculier et al. 1993] | ||
+ | |1987 to not reported | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | | | + | |Multi-drug regimen |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |[https://www. | + | |} |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Doxorubicin (Adriamycin)]] 50 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 | ||
+ | '''21-day cycle for 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #6, 1000/50/600 {{#subobject:94yb81|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527803/ Baka et al. 2008] | ||
|1999-2005 | |1999-2005 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | | | + | |[[Small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29_2|EP]] |
− | | style="background-color:#ffffbf" |Did not meet primary endpoint of | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS12 |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Doxorubicin (Adriamycin)]] | + | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Etoposide (Vepesid)]] | + | *[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once on day 1, then 240 mg/m<sup>2</sup> PO once per day on days 2 & 3 |
− | + | '''21-day cycle for 6 cycles''' | |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Bunn PA Jr, Greco FA, Einhorn L. Cyclophosphamide, doxorubicin, and etoposide as first-line therapy in the treatment of small-cell lung cancer. Semin Oncol. 1986 Sep;13(3 Suppl 3):45-53. [https://pubmed.ncbi.nlm.nih.gov/3020700 PubMed] | + | # Klastersky J, Sculier JP, Dumont JP, Becquart D, Vandermoten G, Rocmans P, Michel J, Longeval E, Dalesio O. Combination chemotherapy with adriamycin, etoposide, and cyclophosphamide for small cell carcinoma of the lung: a study by the EORTC Lung Cancer Working Party (Belgium). Cancer. 1985 Jul 1;56(1):71-5. [https://doi.org/10.1002/1097-0142%2819850701%2956%3A1%3C71%3A%3AAID-CNCR2820560112%3E3.0.CO%3B2-9 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2988738/ PubMed] |
− | # Postmus PE, Scagliotti G, Groen HJ, Gozzelino F, Burghouts JT, Curran D, Sahmoud T, Kirkpatrick A, Giaccone G, Splinter TA. Standard versus alternating non-cross-resistant chemotherapy in extensive small cell lung cancer: an EORTC phase III trial. Eur J Cancer. 1996 Aug;32A(9):1498-503. [https:// | + | # Bunn PA Jr, Greco FA, Einhorn L. Cyclophosphamide, doxorubicin, and etoposide as first-line therapy in the treatment of small-cell lung cancer. Semin Oncol. 1986 Sep;13(3 Suppl 3):45-53. [https://pubmed.ncbi.nlm.nih.gov/3020700/ PubMed] |
− | # '''EORTC 08923:''' Ardizzoni A, Tjan-Heijnen VC, Postmus PE, Buchholz E, Biesma B, Karnicka-Mlodkowska H, Dziadziuszko R, Burghouts J, Van Meerbeeck JP, Gans S, Legrand C, Debruyne C, Giaccone G, Manegold C; [[Study_Groups#EORTC|EORTC]]-Lung Cancer Group. Standard versus intensified chemotherapy with granulocyte colony-stimulating factor support in small-cell lung cancer: a prospective European Organisation for Research and Treatment of Cancer-Lung Cancer Group Phase III Trial-08923. J Clin Oncol. 2002 Oct 1;20(19):3947-55. [https://doi.org/10.1200/JCO.2002.02.069 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12351591 PubMed] | + | # Sculier JP, Paesmans M, Bureau G, Dabouis G, Libert P, Vandermoten G, Van Cutsem O, Berchier MC, Ries F, Michel J, Sergysels R, Mommen P, Klastersky J. Multiple-drug weekly chemotherapy versus standard combination regimen in small-cell lung cancer: a phase III randomized study conducted by the European Lung Cancer Working Party. J Clin Oncol. 1993 Oct;11(10):1858-65. [https://doi.org/10.1200/JCO.1993.11.10.1858 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8410110/ PubMed] |
− | # '''CKVO-9802:''' de Jong WK, Groen HJ, Koolen MG, Biesma B, Willems LN, Kwa HB, van Bochove A, van Tinteren H, Smit EF. Phase III study of cyclophosphamide, doxorubicin, and etoposide compared with carboplatin and paclitaxel in patients with extensive disease small-cell lung cancer. Eur J Cancer. 2007 Nov;43(16):2345-50. Epub 2007 Sep 10. [https:// | + | # Postmus PE, Scagliotti G, Groen HJ, Gozzelino F, Burghouts JT, Curran D, Sahmoud T, Kirkpatrick A, Giaccone G, Splinter TA. Standard versus alternating non-cross-resistant chemotherapy in extensive small cell lung cancer: an EORTC phase III trial. Eur J Cancer. 1996 Aug;32A(9):1498-503. [https://doi.org/10.1016/0959-8049(96)00145-1 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8911108/ PubMed] |
+ | # '''EORTC 08923:''' Ardizzoni A, Tjan-Heijnen VC, Postmus PE, Buchholz E, Biesma B, Karnicka-Mlodkowska H, Dziadziuszko R, Burghouts J, Van Meerbeeck JP, Gans S, Legrand C, Debruyne C, Giaccone G, Manegold C; [[Study_Groups#EORTC|EORTC]]-Lung Cancer Group. Standard versus intensified chemotherapy with granulocyte colony-stimulating factor support in small-cell lung cancer: a prospective European Organisation for Research and Treatment of Cancer-Lung Cancer Group Phase III Trial-08923. J Clin Oncol. 2002 Oct 1;20(19):3947-55. [https://doi.org/10.1200/JCO.2002.02.069 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12351591/ PubMed] | ||
+ | #'''MRC LU21:''' Thatcher N, Qian W, Clark PI, Hopwood P, Sambrook RJ, Owens R, Stephens RJ, Girling DJ. Ifosfamide, carboplatin, and etoposide with midcycle vincristine versus standard chemotherapy in patients with small-cell lung cancer and good performance status: clinical and quality-of-life results of the British Medical Research Council multicenter randomized LU21 trial. J Clin Oncol. 2005 Nov 20;23(33):8371-9. [https://doi.org/10.1200/jco.2004.00.9969 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16293867/ PubMed] [https://clinicaltrials.gov/study/NCT00002822 NCT00002822] | ||
+ | # '''CKVO-9802:''' de Jong WK, Groen HJ, Koolen MG, Biesma B, Willems LN, Kwa HB, van Bochove A, van Tinteren H, Smit EF. Phase III study of cyclophosphamide, doxorubicin, and etoposide compared with carboplatin and paclitaxel in patients with extensive disease small-cell lung cancer. Eur J Cancer. 2007 Nov;43(16):2345-50. Epub 2007 Sep 10. [https://doi.org/10.1016/j.ejca.2007.07.029 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17826977/ PubMed] [https://clinicaltrials.gov/study/NCT00003696 NCT00003696] | ||
+ | # Baka S, Califano R, Ferraldeschi R, Aschroft L, Thatcher N, Taylor P, Faivre-Finn C, Blackhall F, Lorigan P. Phase III randomised trial of doxorubicin-based chemotherapy compared with platinum-based chemotherapy in small-cell lung cancer. Br J Cancer. 2008 Aug 5;99(3):442-7. [https://doi.org/10.1038/sj.bjc.6604480 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527803/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18665190/ PubMed] | ||
==CEV (Cyclophosphamide/Epirubicin) {{#subobject:ec643a|Regimen=1}}== | ==CEV (Cyclophosphamide/Epirubicin) {{#subobject:ec643a|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CEV: '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin, '''<u>V</u>'''incristine | CEV: '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin, '''<u>V</u>'''incristine | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:e4488b|Variant=1}}=== | ===Regimen {{#subobject:e4488b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 631: | Line 781: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Epirubicin (Ellence)]] | + | *[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Vincristine (Oncovin)]] | + | *[[Vincristine (Oncovin)]] 2 mg IV once on day 1 |
− | + | '''21-day cycle for up to 5 cycles''' | |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # 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] ''' | + | # Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. [https://doi.org/10.1200/jco.2002.12.111 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12488411/ PubMed] |
==CEV (Cyclophosphamide/Etoposide) {{#subobject:eu7r3a|Regimen=1}}== | ==CEV (Cyclophosphamide/Etoposide) {{#subobject:eu7r3a|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CEV: '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide, '''<u>V</u>'''incristine | CEV: '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide, '''<u>V</u>'''incristine | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:yr328b|Variant=1}}=== | ===Regimen {{#subobject:yr328b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 654: | Line 803: | ||
|- | |- | ||
|[https://doi.org/10.1200/JCO.1989.7.4.450 Hong et al. 1989] | |[https://doi.org/10.1200/JCO.1989.7.4.450 Hong et al. 1989] | ||
− | | | + | |Not reported |
| style="background-color:#1a9851" |Randomized (E-esc) | | style="background-color:#1a9851" |Randomized (E-esc) | ||
− | |1. [[#CAV_2|CAV]]<br> 2. CV | + | |1. [[#CAV_2|CAV]]<br>2. [[#Cyclophosphamide_.26_Vincristine_.28CV.29_888|CV]] |
| style="background-color:#1a9850" |Superior OS | | style="background-color:#1a9850" |Superior OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Etoposide (Vepesid)]] | + | *[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> IV once on day 1, then 100 mg/m<sup>2</sup> PO once per day on days 2 to 5 |
− | *[[Vincristine (Oncovin)]] | + | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 |
− | + | '''21-day cycles''' | |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Hong WK, Nicaise C, Lawson R, Maroun JA, Comis R, Speer J, Luedke D, Hurtubise M, Lanzotti V, Goodlow J, Rozencweig M; Bristol Lung Cancer Study Group. Etoposide combined with cyclophosphamide plus vincristine compared with doxorubicin plus cyclophosphamide plus vincristine and with high-dose cyclophosphamide plus vincristine in the treatment of small-cell carcinoma of the lung: a randomized trial of the Bristol Lung Cancer Study Group. J Clin Oncol. 1989 Apr;7(4):450-6. [https://doi.org/10.1200/JCO.1989.7.4.450 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2538577 PubMed] | + | # Hong WK, Nicaise C, Lawson R, Maroun JA, Comis R, Speer J, Luedke D, Hurtubise M, Lanzotti V, Goodlow J, Rozencweig M; Bristol Lung Cancer Study Group. Etoposide combined with cyclophosphamide plus vincristine compared with doxorubicin plus cyclophosphamide plus vincristine and with high-dose cyclophosphamide plus vincristine in the treatment of small-cell carcinoma of the lung: a randomized trial of the Bristol Lung Cancer Study Group. J Clin Oncol. 1989 Apr;7(4):450-6. [https://doi.org/10.1200/JCO.1989.7.4.450 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2538577/ PubMed] |
==CEV (Carboplatin/Etoposide) {{#subobject:ec321a|Regimen=1}}== | ==CEV (Carboplatin/Etoposide) {{#subobject:ec321a|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CEV: '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide, '''<u>V</u>'''incristine | CEV: '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide, '''<u>V</u>'''incristine | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:e4488b|Variant=1}}=== | ===Regimen {{#subobject:e4488b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1093/jnci/djg017 Reck et al. 2003] |
− | |1998-1999 | + | |1998-01 to 1999-12 |
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#PCE|TEC]] | |[[#PCE|TEC]] | ||
Line 689: | Line 837: | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: cycle duration was not specified.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Carboplatin (Paraplatin)]] | + | *[[Carboplatin (Paraplatin)]] AUC 5 IV over 30 to 60 minutes once on day 1 |
− | *[[Etoposide (Vepesid)]] | + | *[[Etoposide (Vepesid)]] by the following stage-specific criteria: |
− | *[[Vincristine (Oncovin)]] | + | **Stage I-IIIB: 159 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3 |
− | + | **Stage IV: 125 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3 | |
+ | *[[Vincristine (Oncovin)]] 2 mg IV once per day on days 1 & 8 | ||
+ | '''2 or more cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Reck M, von Pawel J, Macha HN, Kaukel E, Deppermann KM, Bonnet R, Ulm K, Hessler S, Gatzemeier U. Randomized phase III trial of paclitaxel, etoposide, and carboplatin versus carboplatin, etoposide, and vincristine in patients with small-cell lung cancer. J Natl Cancer Inst. 2003 Aug 6;95(15):1118-27. [https:// | + | # Reck M, von Pawel J, Macha HN, Kaukel E, Deppermann KM, Bonnet R, Ulm K, Hessler S, Gatzemeier U. Randomized phase III trial of paclitaxel, etoposide, and carboplatin versus carboplatin, etoposide, and vincristine in patients with small-cell lung cancer. J Natl Cancer Inst. 2003 Aug 6;95(15):1118-27. [https://doi.org/10.1093/jnci/djg017 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12902441/ PubMed] |
− | + | ==Cisplatin & Etoposide (EP) & Pembrolizumab {{#subobject:eeja26|Regimen=1}}== | |
− | ==Cisplatin | ||
− | |||
− | |||
− | |||
− | |||
EP & Pembrolizumab: '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin), Pembrolizumab | EP & Pembrolizumab: '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin), Pembrolizumab | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:3ci91m|Variant=1}}=== | ===Regimen {{#subobject:3ci91m|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ Rudin et al. 2020 (KEYNOTE-604)] |
− | |2017-2018 | + | |2017-05-15 to 2018-07-30 |
|style="background-color:#1a9851" |Phase 3 (E-esc) | |style="background-color:#1a9851" |Phase 3 (E-esc) | ||
− | | | + | |1a. [[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]] |
− | | style="background-color:# | + | | style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup> (co-primary endpoint)<br>OS24: 22.5% vs 11.2%<br>(HR 0.80, 95% CI 0.64-0.98) |
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>This result did not meet the pre-specified threshold for statistical significance, and was the basis for withdrawal of the FDA indication.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] as follows: | *[[Cisplatin (Platinol)]] as follows: | ||
Line 725: | Line 876: | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1 | *[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1 | ||
− | |||
'''21-day cycle for up to 35 cycles (2 years)''' | '''21-day cycle for up to 35 cycles (2 years)''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''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] [ | + | # '''KEYNOTE-604:''' Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gümüş M, Kato T, Kalemkerian GP, Luo Y, Ebiana V, Pietanza MC, Kim HR; KEYNOTE-604 Investigators. Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. J Clin Oncol. 2020 Jul 20;38(21):2369-2379. Epub 2020 May 29. [https://doi.org/10.1200/jco.20.00793 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32468956/ PubMed] [https://clinicaltrials.gov/study/NCT03066778 NCT03066778] |
− | |||
==Cyclophosphamide & Lomustine {{#subobject:ab365b|Regimen=1}}== | ==Cyclophosphamide & Lomustine {{#subobject:ab365b|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#ee6b6e"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:th1b8b|Variant=1}}=== | ===Regimen {{#subobject:th1b8b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 750: | Line 897: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 700 mg/m<sup>2</sup> IV once per day on days 1 & 22 |
− | *[[Lomustine (CCNU)]] | + | *[[Lomustine (CCNU)]] 70 mg/m<sup>2</sup> PO once on day 1 |
− | + | '''42-day cycles''' | |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | #Ettinger DS, Lagakos S; ECOG. Phase III study of CCNU, cyclophosphamide, adriamycin, vincristine, and VP-16 in small-cell carcinoma of the lung. Cancer. 1982 Apr 15;49(8):1544-54. [https://doi.org/10.1002/1097-0142(19820415)49:8%3C1544::aid-cncr2820490806%3E3.0.co;2-j link to original article] [https://pubmed.ncbi.nlm.nih.gov/6279269/ PubMed] | + | #Ettinger DS, Lagakos S; ECOG. Phase III study of CCNU, cyclophosphamide, adriamycin, vincristine, and VP-16 in small-cell carcinoma of the lung. Cancer. 1982 Apr 15;49(8):1544-54. [https://doi.org/10.1002/1097-0142(19820415)49:8%3C1544::aid-cncr2820490806%3E3.0.co;2-j link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/6279269/ PubMed] |
==Cyclophosphamide, Lomustine, Methotrexate {{#subobject:ab343a|Regimen=1}}== | ==Cyclophosphamide, Lomustine, Methotrexate {{#subobject:ab343a|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#ee6b6e"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:e4338b|Variant=1}}=== | ===Regimen {{#subobject:e4338b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1001/jama.1979.03290430031019 Cohen et al. 1979] |
|1975-1977 | |1975-1977 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
Line 777: | Line 923: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 1500 mg/m<sup>2</sup> IV once on day 1, then 1000 mg/m<sup>2</sup> IV once on day 22 |
− | *[[Lomustine (CCNU)]] | + | *[[Lomustine (CCNU)]] 100 mg/m<sup>2</sup> PO once on day 1 |
− | *[[Methotrexate (MTX)]] | + | *[[Methotrexate (MTX)]] 15 mg/m<sup>2</sup> (route not specified) on days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32 (twice per week) |
− | + | '''42-day course''' | |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Cohen MH, Chretien PB, Ihde DC, Fossieck BE Jr, Makuch R, Bunn PA Jr, Johnston AV, Shackney SE, Matthews MJ, Lipson SD, Kenady DE, Minna JD. Thymosin fraction V and intensive combination chemotherapy: prolonging the survival of patients with small-cell lung cancer. JAMA. 1979 Apr 27;241(17):1813-5. [https:// | + | # Cohen MH, Chretien PB, Ihde DC, Fossieck BE Jr, Makuch R, Bunn PA Jr, Johnston AV, Shackney SE, Matthews MJ, Lipson SD, Kenady DE, Minna JD. Thymosin fraction V and intensive combination chemotherapy: prolonging the survival of patients with small-cell lung cancer. JAMA. 1979 Apr 27;241(17):1813-5. [https://doi.org/10.1001/jama.1979.03290430031019 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/219267/ PubMed] |
==Cyclophosphamide, Lomustine, Procarbazine {{#subobject:abug71|Regimen=1}}== | ==Cyclophosphamide, Lomustine, Procarbazine {{#subobject:abug71|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#ee6b6e"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:thg1tb|Variant=1}}=== | ===Regimen {{#subobject:thg1tb|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 805: | Line 950: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 700 mg/m<sup>2</sup> IV once per day on days 1 & 22 |
− | *[[Lomustine (CCNU)]] | + | *[[Lomustine (CCNU)]] 70 mg/m<sup>2</sup> PO once on day 1 |
− | *[[Procarbazine (Matulane)]] | + | *[[Procarbazine (Matulane)]] 70 mg/m<sup>2</sup> PO once per day on days 2 to 8, 22 to 28 |
+ | '''42-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | #Ettinger DS, Lagakos S; ECOG. Phase III study of CCNU, cyclophosphamide, adriamycin, vincristine, and VP-16 in small-cell carcinoma of the lung. Cancer. 1982 Apr 15;49(8):1544-54. [https://doi.org/10.1002/1097-0142(19820415)49:8%3C1544::aid-cncr2820490806%3E3.0.co;2-j link to original article] [https://pubmed.ncbi.nlm.nih.gov/6279269/ PubMed] | + | #Ettinger DS, Lagakos S; ECOG. Phase III study of CCNU, cyclophosphamide, adriamycin, vincristine, and VP-16 in small-cell carcinoma of the lung. Cancer. 1982 Apr 15;49(8):1544-54. [https://doi.org/10.1002/1097-0142(19820415)49:8%3C1544::aid-cncr2820490806%3E3.0.co;2-j link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/6279269/ PubMed] |
− | |||
==EVI {{#subobject:21fa55|Regimen=1}}== | ==EVI {{#subobject:21fa55|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
EVI: '''<u>E</u>'''pirubicin, '''<u>V</u>'''indesine, '''<u>I</u>'''fosfamide | EVI: '''<u>E</u>'''pirubicin, '''<u>V</u>'''indesine, '''<u>I</u>'''fosfamide | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:2fc579|Variant=1}}=== | ===Regimen {{#subobject:2fc579|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 829: | Line 973: | ||
|rowspan=2|1993-2000 | |rowspan=2|1993-2000 | ||
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C) | |rowspan=2 style="background-color:#1a9851" |Phase 3 (C) | ||
− | |1. | + | |1. [[#EVI_.26_GM-CSF_999|EVI & GM-CSF]]; accelerated |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
Line 836: | Line 980: | ||
|- | |- | ||
|} | |} | ||
− | ''Not commonly used but was a comparator arm for at least one RCT; here for reference purposes only.'' | + | ''Note: Not commonly used but was a comparator arm for at least one RCT; here for reference purposes only.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Epirubicin (Ellence)]] | + | *[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Vindesine (Eldisine)]] | + | *[[Vindesine (Eldisine)]] 3 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Ifosfamide (Ifex)]] | + | *[[Ifosfamide (Ifex)]] 5000 mg/m<sup>2</sup> IV once on day 1 |
− | + | ====Supportive therapy==== | |
+ | *[[Mesna (Mesnex)]] | ||
+ | '''21-day cycle for 6 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Sculier JP, Paesmans M, Lecomte J, Van Cutsem O, Lafitte JJ, Berghmans T, Koumakis G, Florin MC, Thiriaux J, Michel J, Giner V, Berchier MC, Mommen P, Ninane V, Klastersky J; European Lung Cancer Working Party. A three-arm phase III randomised trial assessing, in patients with extensive-disease small-cell lung cancer, accelerated chemotherapy with support of haematological growth factor or oral antibiotics. Br J Cancer. 2001 Nov 16;85(10):1444-51. [https:// | + | # Sculier JP, Paesmans M, Lecomte J, Van Cutsem O, Lafitte JJ, Berghmans T, Koumakis G, Florin MC, Thiriaux J, Michel J, Giner V, Berchier MC, Mommen P, Ninane V, Klastersky J; European Lung Cancer Working Party. A three-arm phase III randomised trial assessing, in patients with extensive-disease small-cell lung cancer, accelerated chemotherapy with support of haematological growth factor or oral antibiotics. Br J Cancer. 2001 Nov 16;85(10):1444-51. [https://doi.org/10.1054/bjoc.2001.2114 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363948/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11720426/ PubMed] |
==ICE {{#subobject:f535c2|Regimen=1}}== | ==ICE {{#subobject:f535c2|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
ICE: '''<u>I</u>'''fosfamide, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide | ICE: '''<u>I</u>'''fosfamide, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:b30a1b|Variant=1}}=== | ===Regimen {{#subobject:b30a1b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1093/jnci/dji114 Lorigan et al. 2005] |
|1994-2001 | |1994-2001 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |Dose-dense ICE, then auto HSCT | + | |[[#Dose-dense_ICE.2C_then_auto_HSCT_999|Dose-dense ICE, then auto HSCT]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Ifosfamide (Ifex)]] | + | *[[Ifosfamide (Ifex)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1 |
− | *[[Carboplatin (Paraplatin)]] | + | *[[Carboplatin (Paraplatin)]] 300 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Etoposide (Vepesid)]] | + | *[[Etoposide (Vepesid)]] 180 mg/m<sup>2</sup> IV once per day on days 1 & 2 |
+ | ====Supportive therapy==== | ||
+ | *[[Mesna (Mesnex)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1 | ||
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Lorigan P, Woll PJ, O'Brien ME, Ashcroft LF, Sampson MR, Thatcher N. Randomized phase III trial of dose-dense chemotherapy supported by whole-blood hematopoietic progenitors in better-prognosis small-cell lung cancer. J Natl Cancer Inst. 2005 May 4;97(9):666-74. Erratum in: J Natl Cancer Inst. 2005 Jun 15;97(12):941. [https://doi.org/10.1093/jnci/dji114 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15870437/ PubMed] | ||
+ | ==ICE-V {{#subobject:f5jbc2|Regimen=1}}== | ||
+ | ICE-V: '''<u>I</u>'''fosfamide, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide, '''<u>V</u>'''incristine | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen {{#subobject:tr4a1b|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2004.00.9969 Thatcher et al. 2005 (MRC LU21)] | ||
+ | |1996-03 to 2002-02 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1a. [[#CDE|CDE]]<br>1b. [[Small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29_3|EP]] | ||
+ | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 15.6 vs 11.6 mo<br>(HR 0.74, 95% CI 0.60-0.91) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Ifosfamide (Ifex)]] 5000 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Carboplatin (Paraplatin)]] 300 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 240 mg/m<sup>2</sup> PO once on day 3 | ||
+ | *[[Vincristine (Oncovin)]] 1 mg/m<sup>2</sup> IV once on day 14 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Mesna (Mesnex)]] | ||
+ | '''28-day cycle for 6 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | #'''MRC LU21:''' Thatcher N, Qian W, Clark PI, Hopwood P, Sambrook RJ, Owens R, Stephens RJ, Girling DJ. Ifosfamide, carboplatin, and etoposide with midcycle vincristine versus standard chemotherapy in patients with small-cell lung cancer and good performance status: clinical and quality-of-life results of the British Medical Research Council multicenter randomized LU21 trial. J Clin Oncol. 2005 Nov 20;23(33):8371-9. [https://doi.org/10.1200/jco.2004.00.9969 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16293867/ PubMed] [https://clinicaltrials.gov/study/NCT00002822 NCT00002822] |
==PCDE {{#subobject:b5f588|Regimen=1}}== | ==PCDE {{#subobject:b5f588|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
PCDE: '''<u>P</u>'''latinol (Cisplatin), '''<u>C</u>'''yclophosphamide, Epi'''<u>D</u>'''oxorubicin (Epirubicin), '''<u>E</u>'''toposide | PCDE: '''<u>P</u>'''latinol (Cisplatin), '''<u>C</u>'''yclophosphamide, Epi'''<u>D</u>'''oxorubicin (Epirubicin), '''<u>E</u>'''toposide | ||
− | ===Regimen {{#subobject:bc58e8|Variant=1}}=== | + | <div class="toccolours" style="background-color:#ee6b6e"> |
+ | ===Regimen variant #1, lower-dose etoposide {{#subobject:bc58e8|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 894: | Line 1,071: | ||
| style="background-color:#1a9850" |Superior OS | | style="background-color:#1a9850" |Superior OS | ||
|- | |- | ||
− | |[https:// | + | |} |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 2 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | *[[Epirubicin (Ellence)]] 40 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
+ | '''28-day cycle for 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #2, higher-dose etoposide {{#subobject:ety8e8|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1093/jnci/93.4.300 Pujol et al. 2001 (FNCLCC 95012)] | ||
|1996-1999 | |1996-1999 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
Line 903: | Line 1,098: | ||
|2000-2004 | |2000-2004 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |PCDE & Thalidomide | + | |[[#PCDE_.26_Thalidomide_999|PCDE & Thalidomide]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cisplatin (Platinol)]] | + | *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 2 |
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> IV once per day on days 1 to 3 |
− | *[[Epirubicin (Ellence)]] | + | *[[Epirubicin (Ellence)]] 40 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Etoposide (Vepesid)]] | + | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3 |
− | + | '''28-day cycle for 6 cycles''' | |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Pujol JL, Douillard JY, Rivière A, Quoix E, Lagrange JL, Berthaud P, Bardonnet-Comte M, Polin V, Gautier V, Milleron B, Chomy F, Chomy P, Spaeth D, Le Chevalier T. Dose-intensity of a four-drug chemotherapy regimen with or without recombinant human granulocyte-macrophage colony-stimulating factor in extensive-stage small-cell lung cancer: a multicenter randomized phase III study. J Clin Oncol. 1997 May;15(5):2082-9. [https://doi.org/10.1200/JCO.1997.15.5.2082 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9164221 PubMed] | + | # Pujol JL, Douillard JY, Rivière A, Quoix E, Lagrange JL, Berthaud P, Bardonnet-Comte M, Polin V, Gautier V, Milleron B, Chomy F, Chomy P, Spaeth D, Le Chevalier T. Dose-intensity of a four-drug chemotherapy regimen with or without recombinant human granulocyte-macrophage colony-stimulating factor in extensive-stage small-cell lung cancer: a multicenter randomized phase III study. J Clin Oncol. 1997 May;15(5):2082-9. [https://doi.org/10.1200/JCO.1997.15.5.2082 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9164221/ 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:// | + | # '''FNCLCC 95012:''' Pujol JL, Daurès JP, Rivière A, Quoix E, Westeel V, Quantin X, Breton JL, Lemarié E, Poudenx M, Milleron B, Moro D, Debieuvre D, Le Chevalier T. Etoposide plus cisplatin with or without the combination of 4'-epidoxorubicin plus cyclophosphamide in treatment of extensive small-cell lung cancer: a French Federation of Cancer Institutes multicenter phase III randomized study. J Natl Cancer Inst. 2001 Feb 21;93(4):300-8. [https://doi.org/10.1093/jnci/93.4.300 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11181777/ PubMed] [https://clinicaltrials.gov/study/NCT00003606 NCT00003606] |
− | # '''FNCLCC cleo04/IFCT 00-01:''' Pujol JL, Breton JL, Gervais R, Tanguy ML, Quoix E, David P, Janicot H, Westeel V, Gameroff S, Genève J, Maraninchi D. Phase III double-blind, placebo-controlled study of thalidomide in extensive-disease small-cell lung cancer after response to chemotherapy: an intergroup study FNCLCC cleo04 IFCT 00-01. J Clin Oncol. 2007 Sep 1;25(25):3945-51. [https://doi.org/10.1200/JCO.2007.11.8109 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17761978 PubMed] | + | # '''FNCLCC cleo04/IFCT 00-01:''' Pujol JL, Breton JL, Gervais R, Tanguy ML, Quoix E, David P, Janicot H, Westeel V, Gameroff S, Genève J, Maraninchi D. Phase III double-blind, placebo-controlled study of thalidomide in extensive-disease small-cell lung cancer after response to chemotherapy: an intergroup study FNCLCC cleo04 IFCT 00-01. J Clin Oncol. 2007 Sep 1;25(25):3945-51. [https://doi.org/10.1200/JCO.2007.11.8109 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17761978/ PubMed] |
==PCE {{#subobject:8703fa|Regimen=1}}== | ==PCE {{#subobject:8703fa|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
PCE: '''<u>P</u>'''aclitaxel, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide | PCE: '''<u>P</u>'''aclitaxel, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide | ||
<br>TEC: '''<u>T</u>'''axol (Paclitaxel) '''<u>E</u>'''toposide), '''<u>C</u>'''arboplatin | <br>TEC: '''<u>T</u>'''axol (Paclitaxel) '''<u>E</u>'''toposide), '''<u>C</u>'''arboplatin | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:b2c397|Variant=1}}=== | ===Regimen {{#subobject:b2c397|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1093/jnci/djg017 Reck et al. 2003] |
− | |1998-1999 | + | |1998-01 to 1999-12 |
| style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
|[[#CEV_.28Carboplatin.2FEtoposide.29|CEV]] | |[[#CEV_.28Carboplatin.2FEtoposide.29|CEV]] | ||
Line 940: | Line 1,134: | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: cycle duration was not specified.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Paclitaxel (Taxol)]] | + | *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 4 |
− | *[[Carboplatin (Paraplatin)]] | + | *[[Carboplatin (Paraplatin)]] AUC 5 IV over 30 to 60 minutes once on day 4 |
− | *[[Etoposide (Vepesid)]] | + | *[[Etoposide (Vepesid)]] by the following stage-specific criteria: |
− | + | **Stage I-IIIB: 125 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3 | |
+ | **Stage IV: 102.2 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3 | ||
+ | '''2 or more cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Reck M, von Pawel J, Macha HN, Kaukel E, Deppermann KM, Bonnet R, Ulm K, Hessler S, Gatzemeier U. Randomized phase III trial of paclitaxel, etoposide, and carboplatin versus carboplatin, etoposide, and vincristine in patients with small-cell lung cancer. J Natl Cancer Inst. 2003 Aug 6;95(15):1118-27. [https:// | + | # Reck M, von Pawel J, Macha HN, Kaukel E, Deppermann KM, Bonnet R, Ulm K, Hessler S, Gatzemeier U. Randomized phase III trial of paclitaxel, etoposide, and carboplatin versus carboplatin, etoposide, and vincristine in patients with small-cell lung cancer. J Natl Cancer Inst. 2003 Aug 6;95(15):1118-27. [https://doi.org/10.1093/jnci/djg017 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12902441/ PubMed] |
− | |||
==VIP {{#subobject:8703fa|Regimen=1}}== | ==VIP {{#subobject:8703fa|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
VIP: '''<u>V</u>'''epesid (Etoposide), '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin) | VIP: '''<u>V</u>'''epesid (Etoposide), '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin) | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:b2c397|Variant=1}}=== | ===Regimen {{#subobject:b2c397|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 969: | Line 1,164: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 1 to 4 | *[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 1 to 4 | ||
*[[Ifosfamide (Ifex)]] 1200 mg/m<sup>2</sup> IV once per day on days 1 to 4 | *[[Ifosfamide (Ifex)]] 1200 mg/m<sup>2</sup> IV once per day on days 1 to 4 | ||
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 4 | *[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 4 | ||
− | |||
'''21-day cycle for 4 cycles''' | '''21-day cycle for 4 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # 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] ''' | + | # Loehrer PJ Sr, Ansari R, Gonin R, Monaco F, Fisher W, Sandler A, Einhorn LH; Hoosier Oncology Group. Cisplatin plus etoposide with and without ifosfamide in extensive small-cell lung cancer: a Hoosier Oncology Group study. J Clin Oncol. 1995 Oct;13(10):2594-9. [https://doi.org/10.1200/JCO.1995.13.10.2594 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/7595712/ PubMed] |
− | |||
==VMV-VAC {{#subobject:240cc3|Regimen=1}}== | ==VMV-VAC {{#subobject:240cc3|Regimen=1}}== | ||
− | + | VMV-VAC: '''<u>V</u>'''incristine, '''<u>M</u>'''ethotrexate, '''<u>V</u>'''P-16 (Etoposide), followed by '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide | |
− | + | <div class="toccolours" style="background-color:#ee6b6e"> | |
− | |||
− | |||
− | VMV-VAC: '''<u>V</u>'''incristine, '''<u>M</u>'''ethotrexate, '''<u>V</u>'''P-16 (Etoposide), '''<u>V</u>''' | ||
===Regimen {{#subobject:5dd088|Variant=1}}=== | ===Regimen {{#subobject:5dd088|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 996: | Line 1,187: | ||
|1978-1980 | |1978-1980 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
− | |1. [[#CAV_2|VAC]]<br> 2. VMV | + | |1. [[#CAV_2|VAC]]<br>2. [[#VMV_888|VMV]] |
| style="background-color:#ffffbf" |Did not meet endpoint of OS | | style="background-color:#ffffbf" |Did not meet endpoint of OS | ||
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Vincristine (Oncovin)]] | + | ====Chemotherapy, VMV portion (cycles 1 & 2)==== |
− | *[[Methotrexate (MTX)]] | + | *[[Vincristine (Oncovin)]] 2 mg IV once per day on days 1, 8, 15 |
− | *[[Etoposide (Vepesid)]] | + | *[[Methotrexate (MTX)]] 50 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Doxorubicin (Adriamycin)]] | + | *[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 5 |
− | *[[Cyclophosphamide (Cytoxan)]] | + | ====Chemotherapy, VAC portion (cycles 3 & 4)==== |
− | + | *[[Vincristine (Oncovin)]] 2 mg IV once per day on days 1, 8, 15 | |
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | ||
+ | '''21-day cycle for 4 cycles (VMV x 2; VAC x 2)''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''SWOG S7828:''' Livingston RB, Mira JG, Chen TT, McGavran M, Costanzi JJ, Samson M. Combined modality treatment of extensive small cell lung cancer: a Southwest Oncology Group study. J Clin Oncol. 1984 Jun;2(6):585-90. [https://doi.org/10.1200/JCO.1984.2.6.585 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6327927 PubMed] | + | # '''SWOG S7828:''' Livingston RB, Mira JG, Chen TT, McGavran M, Costanzi JJ, Samson M. Combined modality treatment of extensive small cell lung cancer: a Southwest Oncology Group study. J Clin Oncol. 1984 Jun;2(6):585-90. [https://doi.org/10.1200/JCO.1984.2.6.585 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/6327927/ PubMed] |
=Relapsed or refractory disease= | =Relapsed or refractory disease= | ||
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− | |||
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− | |||
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− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
==CDE {{#subobject:fd0ec6|Regimen=1}}== | ==CDE {{#subobject:fd0ec6|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CDE: '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''oxorubicin, '''<u>E</u>'''toposide | CDE: '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''oxorubicin, '''<u>E</u>'''toposide | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:65860f|Variant=1}}=== | ===Regimen {{#subobject:65860f|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1016/0277-5379(87)90128-3 Postmus et al. 1987] | |[https://doi.org/10.1016/0277-5379(87)90128-3 Postmus et al. 1987] | ||
− | | style="background-color:#91cf61" |Phase | + | |Not reported |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Doxorubicin (Adriamycin)]] | + | *[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Etoposide (Vepesid)]] | + | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 |
− | + | '''21-day cycle for 5 cycles''' | |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Postmus PE, Berendsen HH, van Zandwijk N, Splinter TA, Burghouts JT, Bakker W. Retreatment with the induction regimen in small cell lung cancer relapsing after an initial response to short term chemotherapy. Eur J Cancer Clin Oncol. 1987 Sep;23(9):1409-11. [https://doi.org/10.1016/0277-5379(87)90128-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2824211 PubMed] | + | # Postmus PE, Berendsen HH, van Zandwijk N, Splinter TA, Burghouts JT, Bakker W. Retreatment with the induction regimen in small cell lung cancer relapsing after an initial response to short term chemotherapy. Eur J Cancer Clin Oncol. 1987 Sep;23(9):1409-11. [https://doi.org/10.1016/0277-5379(87)90128-3 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2824211/ PubMed] |
− | |||
==Ipilimumab & Nivolumab {{#subobject:7bc416|Regimen=1}}== | ==Ipilimumab & Nivolumab {{#subobject:7bc416|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#ee6b6e"> | |
− | |||
− | |||
− | |||
===Regimen variant #1 {{#subobject:aa43c1|Variant=1}}=== | ===Regimen variant #1 {{#subobject:aa43c1|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 60%; text-align:center;" | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(16)30098-5 Antonia et al. 2016 (CheckMate 032<sub>SCLC</sub>)] |
|2013-2015 | |2013-2015 | ||
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 1/2 (RT) |
|- | |- | ||
|} | |} | ||
''Note: it is unclear which schedule of ipilimumab & nivolumab is preferred based on the abstract.'' | ''Note: it is unclear which schedule of ipilimumab & nivolumab is preferred based on the abstract.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | *[[Ipilimumab (Yervoy)]] 1 mg/kg IV once on day 1 | + | *[[Ipilimumab (Yervoy)]] as follows: |
+ | **Cycles 1 to 4: 1 mg/kg IV once on day 1 | ||
*[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1 | *[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1 | ||
− | + | '''21-day cycle for 4 cycles, then 14-day cycles''' | |
− | '''21-day cycle for 4 cycles''' | + | </div></div><br> |
− | == | + | <div class="toccolours" style="background-color:#ee6b6e"> |
− | |||
− | |||
===Regimen variant #2 {{#subobject:b6a1ee|Variant=1}}=== | ===Regimen variant #2 {{#subobject:b6a1ee|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 60%; text-align:center;" | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(16)30098-5 Antonia et al. 2016 (CheckMate 032<sub>SCLC</sub>)] |
|2013-2015 | |2013-2015 | ||
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 1/2 (RT) |
|- | |- | ||
|} | |} | ||
''Note: it is unclear which schedule of ipilimumab & nivolumab is preferred based on the abstract.'' | ''Note: it is unclear which schedule of ipilimumab & nivolumab is preferred based on the abstract.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | *[[Ipilimumab (Yervoy)]] 3 mg/kg IV once on day 1 | + | *[[Ipilimumab (Yervoy)]] as follows: |
− | *[[Nivolumab (Opdivo)]] 1 mg/kg IV once on day 1 | + | **Cycles 1 to 4: 3 mg/kg IV once on day 1 |
− | + | *[[Nivolumab (Opdivo)]] as follows: | |
− | '''21-day cycle for 4 cycles''' | + | **Cycles 1 to 4: 1 mg/kg IV once on day 1 |
− | + | **Cycle 5 onwards: 3 mg/kg IV once on day 1 | |
− | + | '''21-day cycle for 4 cycles, then 14-day cycles''' | |
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''CheckMate 032:''' Antonia SJ, López-Martin JA, Bendell J, Ott PA, Taylor M, Eder JP, Jäger D, Pietanza MC, Le DT, de Braud F, Morse MA, Ascierto PA, Horn L, Amin A, Pillai RN, Evans J, Chau I, Bono P, Atmaca A, Sharma P, Harbison CT, Lin CS, Christensen O, Calvo E. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016 Jul;17(7):883-95. Epub 2016 Jun 4. [https:// | + | # '''CheckMate 032<sub>SCLC</sub>:''' Antonia SJ, López-Martin JA, Bendell J, Ott PA, Taylor M, Eder JP, Jäger D, Pietanza MC, Le DT, de Braud F, Morse MA, Ascierto PA, Horn L, Amin A, Pillai RN, Evans J, Chau I, Bono P, Atmaca A, Sharma P, Harbison CT, Lin CS, Christensen O, Calvo E. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016 Jul;17(7):883-95. Epub 2016 Jun 4. [https://doi.org/10.1016/S1470-2045(16)30098-5 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27269741/ PubMed] [https://clinicaltrials.gov/study/NCT01928394 NCT01928394] |
− | + | ##'''Update:''' Ready NE, Ott PA, Hellmann MD, Zugazagoitia J, Hann CL, de Braud F, Antonia SJ, Ascierto PA, Moreno V, Atmaca A, Salvagni S, Taylor M, Amin A, Camidge DR, Horn L, Calvo E, Li A, Lin WH, Callahan MK, Spigel DR. Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer: Results From the CheckMate 032 Randomized Cohort. J Thorac Oncol. 2020 Mar;15(3):426-435. Epub 2019 Oct 17. [https://doi.org/10.1016/j.jtho.2019.10.004 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31629915/ PubMed] | |
==Nivolumab monotherapy {{#subobject:67a13c|Regimen=1}}== | ==Nivolumab monotherapy {{#subobject:67a13c|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#ee6b6e"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:5a9324|Variant=1}}=== | ===Regimen {{#subobject:5a9324|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 60%; text-align:center;" | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(16)30098-5 Antonia et al. 2016 (CheckMate 032<sub>SCLC</sub>)] |
|2013-2015 | |2013-2015 | ||
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 1/2 (RT) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
*[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1 | *[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1 | ||
− | |||
'''14-day cycles''' | '''14-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''CheckMate 032:''' Antonia SJ, López-Martin JA, Bendell J, Ott PA, Taylor M, Eder JP, Jäger D, Pietanza MC, Le DT, de Braud F, Morse MA, Ascierto PA, Horn L, Amin A, Pillai RN, Evans J, Chau I, Bono P, Atmaca A, Sharma P, Harbison CT, Lin CS, Christensen O, Calvo E. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016 Jul;17(7):883-95. Epub 2016 Jun 4. [https:// | + | # '''CheckMate 032<sub>SCLC</sub>:''' Antonia SJ, López-Martin JA, Bendell J, Ott PA, Taylor M, Eder JP, Jäger D, Pietanza MC, Le DT, de Braud F, Morse MA, Ascierto PA, Horn L, Amin A, Pillai RN, Evans J, Chau I, Bono P, Atmaca A, Sharma P, Harbison CT, Lin CS, Christensen O, Calvo E. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016 Jul;17(7):883-95. Epub 2016 Jun 4. [https://doi.org/10.1016/S1470-2045(16)30098-5 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27269741/ PubMed] [https://clinicaltrials.gov/study/NCT01928394 NCT01928394] |
+ | ##'''Update:''' Ready NE, Ott PA, Hellmann MD, Zugazagoitia J, Hann CL, de Braud F, Antonia SJ, Ascierto PA, Moreno V, Atmaca A, Salvagni S, Taylor M, Amin A, Camidge DR, Horn L, Calvo E, Li A, Lin WH, Callahan MK, Spigel DR. Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer: Results From the CheckMate 032 Randomized Cohort. J Thorac Oncol. 2020 Mar;15(3):426-435. Epub 2019 Oct 17. [https://doi.org/10.1016/j.jtho.2019.10.004 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31629915/ PubMed] | ||
==Pembrolizumab monotherapy {{#subobject:bc1cf4|Regimen=1}}== | ==Pembrolizumab monotherapy {{#subobject:bc1cf4|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#ee6b6e"> | |
− | |||
− | |||
− | |||
===Regimen variant #1, 10 mg/kg q2wk {{#subobject:96a1cg|Variant=1}}=== | ===Regimen variant #1, 10 mg/kg q2wk {{#subobject:96a1cg|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 60%; text-align:center;" | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https://doi.org/10.1200/JCO.2017.72.5069 Ott et al. 2017c (KEYNOTE-028)] | + | |[https://doi.org/10.1200/JCO.2017.72.5069 Ott et al. 2017c (KEYNOTE-028<sub>SCLC</sub>)] |
|2014-2015 | |2014-2015 | ||
| style="background-color:#91cf61" |Phase 1b (RT) | | style="background-color:#91cf61" |Phase 1b (RT) | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
*[[Pembrolizumab (Keytruda)]] 10 mg/kg IV once on day 1 | *[[Pembrolizumab (Keytruda)]] 10 mg/kg IV once on day 1 | ||
− | |||
'''14-day cycle for up to 52 cycles (2 years)''' | '''14-day cycle for up to 52 cycles (2 years)''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen variant #2, 200 mg q3wk {{#subobject:ac7fd1|Variant=1}}=== | ===Regimen variant #2, 200 mg q3wk {{#subobject:ac7fd1|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
Line 1,194: | Line 1,325: | ||
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |KEYNOTE-158 | + | |[https://www.clinicaltrials.gov/study/NCT02628067 Awaiting publication (KEYNOTE-158<sub>SCLC</sub>)] |
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 |
|- | |- | ||
|} | |} | ||
− | ''Note: this arm of KEYNOTE-158 has not been published yet, to our knowledge.'' | + | ''Note: this arm of KEYNOTE-158 has not been published yet, to our knowledge. KEYNOTE-158 was a basket study with multiple arms of different enrollment periods.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1 | *[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1 | ||
− | |||
'''21-day cycle for up to 35 cycles (2 years)''' | '''21-day cycle for up to 35 cycles (2 years)''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''KEYNOTE-028:''' Ott PA, Elez E, Hiret S, Kim DW, Morosky A, Saraf S, Piperdi B, Mehnert JM. Pembrolizumab in patients With extensive-stage small-cell lung cancer: results from the phase Ib KEYNOTE-028 study. J Clin Oncol. 2017 Dec 1;35(34):3823-3829. Epub 2017 Aug 16. [https://doi.org/10.1200/JCO.2017.72.5069 link to original article] ''' | + | # '''KEYNOTE-028<sub>SCLC</sub>:''' Ott PA, Elez E, Hiret S, Kim DW, Morosky A, Saraf S, Piperdi B, Mehnert JM. Pembrolizumab in patients With extensive-stage small-cell lung cancer: results from the phase Ib KEYNOTE-028 study. J Clin Oncol. 2017 Dec 1;35(34):3823-3829. Epub 2017 Aug 16. [https://doi.org/10.1200/JCO.2017.72.5069 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28813164/ PubMed] [https://clinicaltrials.gov/study/NCT02054806 NCT02054806] |
− | # '''KEYNOTE-158:''' NCT02628067 | + | # '''KEYNOTE-158<sub>SCLC</sub>:''' [https://clinicaltrials.gov/study/NCT02628067 NCT02628067] |
− | = | + | =Relapsed or refractory disease, second-line= |
− | ==Nivolumab monotherapy {{#subobject: | + | ==Nivolumab monotherapy {{#subobject:ig833c|Regimen=1}}== |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#ee6b6e"> |
+ | ===Regimen {{#subobject:5a8guac|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.annonc.2021.01.071 Spigel et al. 2021 (CheckMate 331)] |
− | | | + | |2015-2017 |
− | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | |
− | + | |1a. [[Small_cell_lung_cancer#Amrubicin_monotherapy|Amrubicin]]<br>1b. [[Small_cell_lung_cancer#Topotecan_monotherapy|Topotecan]] | |
− | + | | style="background-color:#d9ef8b" |Might have superior OS (primary endpoint)<br>Median OS: 7.5 vs 8.4 mo<br>(HR 0.86, 95% CI 0.72-1.04) | |
− | |||
− | |||
− | | | ||
− | |||
− | |||
− | | style="background-color:# | ||
|- | |- | ||
|} | |} | ||
− | == | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | |||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | *[[Nivolumab (Opdivo)]] | + | *[[Nivolumab (Opdivo)]] 240 mg IV over 30 minutes once on day 1 |
− | |||
'''14-day cycles''' | '''14-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''CheckMate | + | # '''CheckMate 331:''' Spigel DR, Vicente D, Ciuleanu TE, Gettinger S, Peters S, Horn L, Audigier-Valette C, Pardo Aranda N, Juan-Vidal O, Cheng Y, Zhang H, Shi M, Luft A, Wolf J, Antonia S, Nakagawa K, Fairchild J, Baudelet C, Pandya D, Doshi P, Chang H, Reck M. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331. Ann Oncol. 2021 May;32(5):631-641. Epub 2021 Feb 1. [https://doi.org/10.1016/j.annonc.2021.01.071 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33539946/ PubMed] [https://clinicaltrials.gov/study/NCT02481830 NCT02481830] |
− | |||
[[Category:Small cell lung cancer regimens]] | [[Category:Small cell lung cancer regimens]] | ||
[[Category:Historical regimens]] | [[Category:Historical regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Lung cancers]] | [[Category:Lung cancers]] |
Latest revision as of 11:36, 25 July 2024
The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main SCLC page for current regimens.
31 regimens on this page
39 variants on this page
|
Limited stage, induction
CAV
CAV: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Johnson et al. 1993 | 1982-1985 | Phase 3 (C) | CAV & RT | Might have inferior OS24 |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 (maximum dose of 2000 mg) IV once on day 1
- Doxorubicin (Adriamycin) 40 mg/m2 (maximum dose of 100 mg) IV once on day 1
- Vincristine (Oncovin) 1 mg/m2 (maximum dose of 2 mg) IV once on day 1
21-day cycle for 6 cycles
References
- Johnson DH, Bass D, Einhorn LH, Crawford J, Perez CA, Bartolucci A, Omura GA, Greco FA; Southeastern Cancer Study Group. Combination chemotherapy with or without thoracic radiotherapy in limited-stage small-cell lung cancer: a randomized trial of the Southeastern Cancer Study Group. J Clin Oncol. 1993 Jul;11(7):1223-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
CAV/PE
CAV/PE: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine alternating with Platinol (Cisplatin) & Etoposide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Feld et al. 1987 | 1981-1984 | Randomized (E-switch-ic) | CAV-PE | Did not meet efficacy endpoints |
Chemotherapy, CAV portion (cycles 1, 3, 5)
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
Chemotherapy, PE portion (cycles 2, 4, 6)
- Cisplatin (Platinol) 25 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV over 40 to 60 minutes once on day 1
21-day cycle for 6 cycles
References
- Feld R, Evans WK, Coy P, Hodson I, MacDonald AS, Osoba D, Payne D, Shelley W, Pater JL. Canadian multicenter randomized trial comparing sequential and alternating administration of two non-cross-resistant chemotherapy combinations in patients with limited small-cell carcinoma of the lung. J Clin Oncol. 1987 Sep;5(9):1401-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
MACC
MACC: Methotrexate, Adriamycin (Doxorubicin), Cyclophosphamide, CCNU (Lomustine)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Maurer et al. 1985 (CALGB 7781) | 1977-1981 | Phase 3 (E-switch-ic) | CCV/AV | Did not meet endpoint of OS |
Chemotherapy
- Methotrexate (MTX) 30 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 35 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 400 mg/m2 IV once on day 1
- Lomustine (CCNU) 30 mg/m2 PO once on day 1
21-day cycle for 2 cycles
Subsequent treatment
- RT consolidation
References
- CALGB 7781: Maurer LH, Pajak T, Eaton W, Comis R, Chahinian P, Faulkner C, Silberfarb PM, Henderson E, Rege VB, Baldwin PE, Weiss R, Rafla S, Prager D, Carey R, Perry M, Choi NC. Combined modality therapy with radiotherapy, chemotherapy, and immunotherapy in limited small-cell carcinoma of the lung: a Phase III Cancer and Leukemia Group B Study. J Clin Oncol. 1985 Jul;3(7):969-76. link to original article dosing details in manuscript have been reviewed by our editors PubMed
VMV/VAC
VMV/VAC: Vincristine, Methotrexate, VP-16 (Etoposide) alternating with Vincristine, Adriamycin (Doxorubicin), Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Kies et al. 1987 | 1979-1982 | Non-randomized part of RCT |
Chemotherapy, VMV portion (cycles 1 & 3)
- Vincristine (Oncovin) as follows:
- Cycle 1: 2 mg IV once per day on days 1, 8, 15
- Methotrexate (MTX) 60 mg/m2 IV once on day 1
- Etoposide (Vepesid) 50 mg/m2 IV once per day on days 1 to 5
Chemotherapy, VAC portion (cycles 2 & 4)
- Vincristine (Oncovin) as follows:
- Cycle 2: 2 mg IV once per day on days 1, 8, 15
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
21-day cycle for 4 cycles (VMV x 2; VAC x 2)
References
- Kies MS, Mira JG, Crowley JJ, Chen TT, Pazdur R, Grozea PN, Rivkin SE, Coltman CA Jr, Ward JH, Livingston RB; SWOG. Multimodal therapy for limited small-cell lung cancer: a randomized study of induction combination chemotherapy with or without thoracic radiation in complete responders; and with wide-field versus reduced-field radiation in partial responders: a Southwest Oncology Group study. J Clin Oncol. 1987 Apr;5(4):592-600. link to original article dosing details in abstract have been reviewed by our editors PubMed
Limited stage, definitive chemoradiotherapy
CCDE & RT
CCDE/RT: Cyclophosphamide, Cisplatin, Doxorubicin, Etoposide, alternating with Radiation Therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Arriagada et al. 1993 | 1988-1991 | Phase 3 (E-esc) | CCDE/RT; lower-dose | Seems to have superior OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) as follows:
- Cycle 1: 300 mg/m2 IV once per day on days 2 to 5
- Cycles 2 to 6: 225 mg/m2 IV once per day on days 2 to 5
- Cisplatin (Platinol) as follows:
- Cycle 1: 100 mg/m2 IV once on day 2
- Cycles 2 to 6: 80 mg/m2 IV once on day 2
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Etoposide (Vepesid) 75 mg/m2 IV once per day on days 1 to 3
Radiotherapy
6 cycles, alternating with radiation after the 2nd, 3rd, and 4th cycle
References
- Arriagada R, Le Chevalier T, Pignon JP, Rivière A, Monnet I, Chomy P, Tuchais C, Tarayre M, Ruffié P. Initial chemotherapeutic doses and survival in patients with limited small-cell lung cancer. N Engl J Med. 1993 Dec 16;329(25):1848-52. link to original article dosing details in manuscript have been reviewed by our editors PubMed
CAV & RT
CAV & RT: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine, Radiation Therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Perez et al. 1984 | 1978-1982 | Randomized (E-esc) | CAV | Might have superior DFS1 |
Jett et al. 1990 | 1979-1986 | Randomized (C) | CAVE & RT | Did not meet endpoint of OS |
Johnson et al. 1993 | 1982-1985 | Phase 3 (E-esc) | CAV | Might have superior OS24 OS24: 33% vs 23.5% |
1It is not clear from the manuscript what the primary endpont of the study was.
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1 mg/m2 IV once on day 1
Radiotherapy
- Concurrent radiation therapy as follows:
- Cycle 1: 3000 cGy in 300 cGy fractions on days 1 to 5, 8 to 12
- Cycle 3: 1500 cGy in 300 cGy fractions on days 1 to 5
21-day cycle for 6 cycles
References
- Perez CA, Einhorn L, Oldham RK, Greco FA, Cohen HJ, Silberman H, Krauss S, Hornback N, Comas F, Omura G, Salter M, Keller JW, McLaren J, Kellermeyer R, Storaasli J, Birch R, Dandy M; Southeastern Cancer Study Group. Randomized trial of radiotherapy to the thorax in limited small-cell carcinoma of the lung treated with multiagent chemotherapy and elective brain irradiation: a preliminary report. J Clin Oncol. 1984 Nov;2(11):1200-8. link to original article PubMed
- Jett JR, Everson L, Therneau TM, Krook JE, Dalton RJ, Marschke RF Jr, Veeder MH, Brunk SF, Mailliard JA, Twito DI, Earle JD, Anderson RT; North Central Cancer Treatment Group. Treatment of limited-stage small-cell lung cancer with cyclophosphamide, doxorubicin, and vincristine with or without etoposide: a randomized trial of the North Central Cancer Treatment Group. J Clin Oncol. 1990 Jan;8(1):33-8. link to original article PubMed
- Johnson DH, Bass D, Einhorn LH, Crawford J, Perez CA, Bartolucci A, Omura GA, Greco FA; Southeastern Cancer Study Group. Combination chemotherapy with or without thoracic radiotherapy in limited-stage small-cell lung cancer: a randomized trial of the Southeastern Cancer Study Group. J Clin Oncol. 1993 Jul;11(7):1223-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
CEV & RT
CEV & RT: Cyclophosphamide, Epirubicin, Vincristine, Radiation Therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Perry et al. 1987 (CALGB 8083) | 1981-1984 | Phase 3 (E-esc) | 1. CEV | Superior OS |
2. CEV, then RT | Not reported | |||
Sundstrøm et al. 2002 | 1989-1994 | Phase 3 (C) | Cisplatin, Etoposide, RT | Inferior OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) as follows:
- Cycles 1 to 3, 5, 6: 1000 mg/m2 IV once on day 1
- Epirubicin (Ellence) as follows:
- Cycles 1 to 3, 5, 6: 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) as follows:
- Cycles 1 to 3, 5, 6: 2 mg IV once on day 1
Radiotherapy
- radiation therapy as follows:
- Cycle 4: 280 cGy once per day on days 1 to 5, 8 to 12, 15 to 19 (4200 cGy total)
21-day cycle for up to 6 cycles
Subsequent treatment
- CALGB 8083: Prophylactic cranial irradiation
- Sundstrøm et al. 2002, patients with CR: Prophylactic cranial irradiation
References
- CALGB 8083: Perry MC, Eaton WL, Propert KJ, Ware JH, Zimmer B, Chahinian AP, Skarin A, Carey RW, Kreisman H, Faulkner C, Comis R, Green MR. Chemotherapy with or without radiation therapy in limited small-cell carcinoma of the lung. N Engl J Med. 1987 Apr 9;316(15):912-8. link to original article PubMed
- Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Cyclophosphamide, Methotrexate, RT
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Thatcher et al. 1982 | 1978-1981 | Non-randomized part of RCT |
Chemotherapy
- Methotrexate (MTX) 100 mg/m2 IV bolus once per day on days 1 & 15
- Cyclophosphamide (Cytoxan) 1500 mg/m2 IV bolus once on day 35, then 2500 mg/m2 IV bolus once on day 56, then 3500 mg/m2 IV bolus once on day 77
Radiotherapy
- Radiation therapy 3.7500 cGy per fraction on days 16 to 19, 22 to 25
11-week course
References
- Maurer LH, Tulloh M, Weiss RB, Blom J, Leone L, Glidewell O, Pajak TF; CALGB. A randomized combined modality trial in small cell carcinoma of the lung: comparison of combination chemotherapy-radiation therapy versus cyclophosphamide-radiation therapy effects of maintenance chemotherapy and prophylactiv whole brain irradiation. Cancer. 1980 Jan 1;45(1):30-9. link to original article PubMed
- Thatcher N, Barber PV, Hunter RD, Carroll KB, Jegarajah S, Wilkinson PM, Crowther D; Manchester Lung Tumour Group. 11-week course of sequential methotrexate, thoracic irradiation, and moderate-dose cyclophosphamide for "limited"-stage small-cell bronchogenic carcinoma: a study from the Manchester Lung Tumour Group. Lancet. 1982 May 8;1(8280):1040-3. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Extensive stage, induction
BACO
BACO: Bleomycin, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Einhorn et al. 1976 | 1973-06 to 1974-07 | Non-randomized |
Chemotherapy
- Bleomycin (Blenoxane) 15 units IV push, given second, 6 hours later
- Doxorubicin (Adriamycin) 50 mg/m2 IV push once on day 1, given with cyclophosphamide
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV push once on day 1, given with doxorubicin
- Vincristine (Oncovin) by the following age-based criteria:
- Younger than 50 years old: 1 mg IV push once on day 2, given first
- 50 years old or older: 0.75 mg IV push once on day 2, given first
21-day cycle for up to 9 cycles
References
- Einhorn LH, Fee WH, Farber MO, Livingston RB, Gottlieb JA. Improved chemotherapy for small-cell undifferentiated lung cancer. JAMA. 1976 Mar 22;235(12):1225-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Carboplatin & Etoposide (CE) & Pembrolizumab
CE & Pembrolizumab: Carboplatin, Etoposide, Pembrolizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rudin et al. 2020 (KEYNOTE-604) | 2017-05-15 to 2018-07-30 | Phase 3 (E-esc) | 1a. CE 1b. EP |
Seems to have superior OS1 (co-primary endpoint) OS24: 22.5% vs 11.2% (HR 0.80, 95% CI 0.64-0.98) |
1This result did not meet the pre-specified threshold for statistical significance, and was the basis for withdrawal of the FDA indication.
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 IV once on day 1
- Etoposide (Vepesid) as follows:
- Cycles 1 to 4: 100 mg/m2 IV once per day on days 1 to 3
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
References
- KEYNOTE-604: Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gümüş M, Kato T, Kalemkerian GP, Luo Y, Ebiana V, Pietanza MC, Kim HR; KEYNOTE-604 Investigators. Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. J Clin Oncol. 2020 Jul 20;38(21):2369-2379. Epub 2020 May 29. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT03066778
CAV
CAV: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine
CAO: Cyclophosphamide, Adriamycin (Doxorubicin), Oncovin (Vincristine)
Regimen variant #1, 1000/40/1, capped by BSA
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Bunn et al. 1986 | Not reported in abstract | Randomized (C) | CDE | Seems to have inferior OS | |
Johnson et al. 1987 | 1982-1984 | Phase 3 (C) | CAV; high-dose | Did not meet endpoint of OS | Less toxic |
Note: the original manuscript with dosing for Bunn et al. 1986 is not available for review.
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 (maximum dose of 2000 mg) IV once on day 1
- Doxorubicin (Adriamycin) 40 mg/m2 (maximum dose of 80 mg) IV once on day 1
- Vincristine (Oncovin) 1 mg/m2 (maximum dose of 2 mg) IV once on day 1
21-day cycle for 6 cycles
Regimen variant #2, 1000/50/1.4, uncapped vincristine
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Ettinger et al. 2002 (ECOG E1588) | 1988-1990 | Phase 3 (C) | 1. Ifosfamide | Did not meet primary endpoint of OS | More toxic |
2. Teniposide | Did not meet primary endpoint of OS | More toxic | |||
Girling 1996 | 1992-1995 | Phase 3 (C) | Etoposide; oral | Seems to have superior OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
21-day cycle for 4 to 6 cycles
Subsequent treatment
- ECOG E1588, CR: CAV continuation x 2 (6 to 8 total), then prophylactic cranial irradiation
- ECOG E1588, PR: CAV continuation until progression of disease, then salvage EP
Regimen variant #3, 1000/50/1.4, capped vincristine
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Ettinger et al. 1990 (ECOG E1582) | 1982-1985 | Phase 3 (C) | CAV/HEM | Inferior OS | Less toxic |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
21-day cycle for 6 to 8 cycles
Regimen variant #4, 1000/50/2, flat-dose vincristine
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Holoye et al. 1977 | 1973-1974 | Non-randomized | |||
Evans et al. 1987 | 1982-1985 | Phase 3 (C) | CAV/PE | Seems to have inferior OS | Similar toxicity |
Maksymiuk et al. 1994 | 1987-1990 | Non-randomized part of RCT |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
21-day cycle for 6 cycles
References
- Holoye PY, Samuels ML, Lanzotti VJ, Smith T, Barkley HT Jr. Combination chemotherapy and radiation therapy for small cell carcinoma. JAMA. 1977 Mar 21;237(12):1221-4. link to original article PubMed
- Bunn PA Jr, Greco FA, Einhorn L. Cyclophosphamide, doxorubicin, and etoposide as first-line therapy in the treatment of small-cell lung cancer. Semin Oncol. 1986 Sep;13(3 Suppl 3):45-53. PubMed
- Evans WK, Feld R, Murray N, Willan A, Coy P, Osoba D, Shepherd FA, Clark DA, Levitt M, MacDonald A, Wilson K, Shelley W, Pater J. Superiority of alternating non-cross-resistant chemotherapy in extensive small cell lung cancer: a multicenter, randomized clinical trial by the National Cancer Institute of Canada. Ann Intern Med. 1987 Oct;107(4):451-8. Erratum in: Ann Intern Med 1988 Mar;108(3):496. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Johnson DH, Einhorn LH, Birch R, Vollmer R, Perez C, Krauss S, Omura G, Greco FA; Southeastern Cancer Study Group. A randomized comparison of high-dose versus conventional-dose cyclophosphamide, doxorubicin, and vincristine for extensive-stage small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol. 1987 Nov;5(11):1731-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- ECOG E1582: Ettinger DS, Finkelstein DM, Abeloff MD, Ruckdeschel JC, Aisner SC, Eggleston JC; ECOG. A randomized comparison of standard chemotherapy versus alternating chemotherapy and maintenance versus no maintenance therapy for extensive-stage small-cell lung cancer: a phase III study of the Eastern Cooperative Oncology Group. J Clin Oncol. 1990 Feb;8(2):230-40. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Maksymiuk AW, Jett JR, Earle JD, Su JQ, Diegert FA, Mailliard JA, Kardinal CG, Krook JE, Veeder MH, Wiesenfeld M, Tschetter LK, Levitt R; North Central Cancer Treatment Group. Sequencing and schedule effects of cisplatin plus etoposide in small-cell lung cancer: results of a North Central Cancer Treatment Group randomized clinical trial. J Clin Oncol. 1994 Jan;12(1):70-6. link to original article PubMed
- Girling DJ; Medical Research Council Lung Cancer Working Party. Comparison of oral etoposide and standard intravenous multidrug chemotherapy for small-cell lung cancer: a stopped multicentre randomised trial. Lancet. 1996 Aug 31;348(9027):563-6. link to original article PubMed
- ECOG E1588: Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; ECOG. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
CAV/PE
CAV/PE: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine alternating with Platinol (Cisplatin) & Etoposide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Goodman et al. 1990 (SWOG S8232) | 1982-1984 | Phase 3 (E-switch-ic) | CAVE | Did not meet primary endpoint of OS |
Evans et al. 1987 | 1982-1985 | Phase 3 (E-switch-ic) | CAV | Seems to have superior OS |
Roth et al. 1992 | 1985-1989 | Phase 3 (E-esc) | 1. CAV 2. EP |
Did not meet primary endpoint of OS50% |
Furuse et al. 1998 (JCOG9106) | 1991-1995 | Phase 3 (C) | CODE | Did not meet primary endpoint of OS50% |
Murray et al. 1999 | 1992-1996 | Phase 3 (C) | CODE | Did not meet primary endpoint of OS |
Chemotherapy, CAV portion (Odd cycles)
- Cyclophosphamide (Cytoxan) 800 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
Chemotherapy, PE portion (Even cycles)
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 (route not specified) once per day on days 1 to 3
21-day cycles
References
- Evans WK, Feld R, Murray N, Willan A, Coy P, Osoba D, Shepherd FA, Clark DA, Levitt M, MacDonald A, Wilson K, Shelley W, Pater J. Superiority of alternating non-cross-resistant chemotherapy in extensive small cell lung cancer: a multicenter, randomized clinical trial by the National Cancer Institute of Canada. Ann Intern Med. 1987 Oct;107(4):451-8. Erratum in: Ann Intern Med 1988 Mar;108(3):496. link to original article dosing details in abstract have been reviewed by our editors PubMed
- SWOG S8232: Goodman GE, Crowley JJ, Blasko JC, Livingston RB, Beck TM, Demattia MD, Bukowski RM. Treatment of limited small-cell lung cancer with etoposide and cisplatin alternating with vincristine, doxorubicin, and cyclophosphamide versus concurrent etoposide, vincristine, doxorubicin, and cyclophosphamide and chest radiotherapy: a Southwest Oncology Group Study. J Clin Oncol. 1990 Jan;8(1):39-47. link to original article PubMed
- Roth BJ, Johnson DH, Einhorn LH, Schacter LP, Cherng NC, Cohen HJ, Crawford J, Randolph JA, Goodlow JL, Broun GO, Omura GA, Greco FA; Southeastern Cancer Study Group. Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol. 1992 Feb;10(2):282-91. link to original article PubMed
- JCOG9106: Furuse K, Fukuoka M, Nishiwaki Y, Kurita Y, Watanabe K, Noda K, Ariyoshi Y, Tamura T, Saijo N; JCOG. Phase III study of intensive weekly chemotherapy with recombinant human granulocyte colony-stimulating factor versus standard chemotherapy in extensive-disease small-cell lung cancer. J Clin Oncol. 1998 Jun;16(6):2126-32. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Murray N, Livingston RB, Shepherd FA, James K, Zee B, Langleben A, Kraut M, Bearden J, Goodwin JW, Grafton C, Turrisi A, Walde D, Croft H, Osoba D, Ottaway J, Gandara D; National Cancer Institute of Canada Clinical Trials Group; SWOG. Randomized study of CODE versus alternating CAV/EP for extensive-stage small-cell lung cancer: an Intergroup Study of the National Cancer Institute of Canada Clinical Trials Group and the Southwest Oncology Group. J Clin Oncol. 1999 Aug;17(8):2300-8. link to original article PubMed
CAVE
CAVE: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine, Etoposide
CAV-E: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine, Etoposide
EVAC: Etoposide, Vincristine, Adriamycin (Doxorubicin), Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Goodman et al. 1990 (SWOG S8232) | 1982-1984 | Phase 3 (C) | CAV/PE | Did not meet primary endpoint of OS |
Tummarello et al. 1997 | 1990-1995 | Phase 3 (C) | CAV-T | Did not meet primary endpoint of OS50% |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1 mg/m2 IV once per day on days 1 & 8
- Etoposide (Vepesid) 75 mg/m2 IV once per day on days 1 to 3
21-day cycle for 6 cycles
References
- SWOG S8232: Goodman GE, Crowley JJ, Blasko JC, Livingston RB, Beck TM, Demattia MD, Bukowski RM. Treatment of limited small-cell lung cancer with etoposide and cisplatin alternating with vincristine, doxorubicin, and cyclophosphamide versus concurrent etoposide, vincristine, doxorubicin, and cyclophosphamide and chest radiotherapy: a Southwest Oncology Group Study. J Clin Oncol. 1990 Jan;8(1):39-47. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Tummarello D, Mari D, Graziano F, Isidori P, Cetto G, Pasini F, Santo A, Cellerino R. A randomized, controlled phase III study of cyclophosphamide, doxorubicin, and vincristine with etoposide (CAV-E) or teniposide (CAV-T), followed by recombinant interferon-alpha maintenance therapy or observation, in small cell lung carcinoma patients with complete responses. Cancer. 1997 Dec 15;80(12):2222-9. link to original article PubMed
CDE
CDE: Cyclophosphamide, Doxorubicin, Etoposide
ACE: Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide
AVE: Adriamycin (Doxorubicin), Vepesid (Etoposide), Endoxan (Cyclophosphamide)
CAE: Cyclophosphamide, Adriamycin (Doxorubicin), Etoposide
Regimen variant #1, 1000/40/480
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Thatcher et al. 2005 (MRC LU21) | 1996-03 to 2002-02 | Phase 3 (C) | ICE-V | Inferior OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 2
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 2 & 3, then 240 mg/m2 PO once on day 3
21-day cycle for 6 cycles
Regimen variant #2, 1000/45/240
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Klastersky et al. 1985 | Not reported | Phase 2 | ORR: 66% |
Note: Used as a comparator arm in older studies. The non-randomized results of Klastersky et al. 1985 established this regimen as a standard control.
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 1
- Etoposide (Vepesid) 80 mg/m2 IV once per day on days 1 to 3
21-day cycle for up to 10 cycles
Regimen variant #3, 1000/45/300
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bunn et al. 1986 | Not reported in abstract | Randomized (E-switch-ic) | CAV | Seems to have superior OS |
Ardizzoni et al. 2002 (EORTC 08923) | 1994-1999 | Phase 3 (C) | CDE; intensified | Did not meet primary endpoint of OS |
de Jong et al. 2007 (CKVO-9802) | 1999-2005 | Phase 3 (C) | CP | Did not meet primary endpoint of PFS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
21-day cycle for 5 cycles
Regimen variant #4, 1000/45/300, alternate etoposide schedule
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Postmus et al. 1996 | 1988-1992 | Phase 3 (C) | CDE/VIMP | Did not meet primary endpoint of OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1, 3, 5
21-day cycle for 5 cycles
Regimen variant #5, 1000/50/240
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sculier et al. 1993 | 1987 to not reported | Phase 3 (C) | Multi-drug regimen | Did not meet primary endpoint of OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Etoposide (Vepesid) 80 mg/m2 IV once per day on days 1 to 3
21-day cycle for 6 cycles
Regimen variant #6, 1000/50/600
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Baka et al. 2008 | 1999-2005 | Phase 3 (C) | EP | Did not meet primary endpoint of OS12 |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once on day 1, then 240 mg/m2 PO once per day on days 2 & 3
21-day cycle for 6 cycles
References
- Klastersky J, Sculier JP, Dumont JP, Becquart D, Vandermoten G, Rocmans P, Michel J, Longeval E, Dalesio O. Combination chemotherapy with adriamycin, etoposide, and cyclophosphamide for small cell carcinoma of the lung: a study by the EORTC Lung Cancer Working Party (Belgium). Cancer. 1985 Jul 1;56(1):71-5. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Bunn PA Jr, Greco FA, Einhorn L. Cyclophosphamide, doxorubicin, and etoposide as first-line therapy in the treatment of small-cell lung cancer. Semin Oncol. 1986 Sep;13(3 Suppl 3):45-53. PubMed
- Sculier JP, Paesmans M, Bureau G, Dabouis G, Libert P, Vandermoten G, Van Cutsem O, Berchier MC, Ries F, Michel J, Sergysels R, Mommen P, Klastersky J. Multiple-drug weekly chemotherapy versus standard combination regimen in small-cell lung cancer: a phase III randomized study conducted by the European Lung Cancer Working Party. J Clin Oncol. 1993 Oct;11(10):1858-65. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Postmus PE, Scagliotti G, Groen HJ, Gozzelino F, Burghouts JT, Curran D, Sahmoud T, Kirkpatrick A, Giaccone G, Splinter TA. Standard versus alternating non-cross-resistant chemotherapy in extensive small cell lung cancer: an EORTC phase III trial. Eur J Cancer. 1996 Aug;32A(9):1498-503. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- EORTC 08923: Ardizzoni A, Tjan-Heijnen VC, Postmus PE, Buchholz E, Biesma B, Karnicka-Mlodkowska H, Dziadziuszko R, Burghouts J, Van Meerbeeck JP, Gans S, Legrand C, Debruyne C, Giaccone G, Manegold C; EORTC-Lung Cancer Group. Standard versus intensified chemotherapy with granulocyte colony-stimulating factor support in small-cell lung cancer: a prospective European Organisation for Research and Treatment of Cancer-Lung Cancer Group Phase III Trial-08923. J Clin Oncol. 2002 Oct 1;20(19):3947-55. link to original article dosing details in abstract have been reviewed by our editors PubMed
- MRC LU21: Thatcher N, Qian W, Clark PI, Hopwood P, Sambrook RJ, Owens R, Stephens RJ, Girling DJ. Ifosfamide, carboplatin, and etoposide with midcycle vincristine versus standard chemotherapy in patients with small-cell lung cancer and good performance status: clinical and quality-of-life results of the British Medical Research Council multicenter randomized LU21 trial. J Clin Oncol. 2005 Nov 20;23(33):8371-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00002822
- CKVO-9802: de Jong WK, Groen HJ, Koolen MG, Biesma B, Willems LN, Kwa HB, van Bochove A, van Tinteren H, Smit EF. Phase III study of cyclophosphamide, doxorubicin, and etoposide compared with carboplatin and paclitaxel in patients with extensive disease small-cell lung cancer. Eur J Cancer. 2007 Nov;43(16):2345-50. Epub 2007 Sep 10. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00003696
- Baka S, Califano R, Ferraldeschi R, Aschroft L, Thatcher N, Taylor P, Faivre-Finn C, Blackhall F, Lorigan P. Phase III randomised trial of doxorubicin-based chemotherapy compared with platinum-based chemotherapy in small-cell lung cancer. Br J Cancer. 2008 Aug 5;99(3):442-7. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
CEV (Cyclophosphamide/Epirubicin)
CEV: Cyclophosphamide, Epirubicin, Vincristine
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sundstrøm et al. 2002 | 1989-1994 | Phase 3 (C) | Cisplatin & Etoposide | Did not meet primary endpoint of OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Epirubicin (Ellence) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
21-day cycle for up to 5 cycles
References
- Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. link to original article dosing details in manuscript have been reviewed by our editors PubMed
CEV (Cyclophosphamide/Etoposide)
CEV: Cyclophosphamide, Etoposide, Vincristine
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hong et al. 1989 | Not reported | Randomized (E-esc) | 1. CAV 2. CV |
Superior OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Etoposide (Vepesid) 50 mg/m2 IV once on day 1, then 100 mg/m2 PO once per day on days 2 to 5
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
21-day cycles
References
- Hong WK, Nicaise C, Lawson R, Maroun JA, Comis R, Speer J, Luedke D, Hurtubise M, Lanzotti V, Goodlow J, Rozencweig M; Bristol Lung Cancer Study Group. Etoposide combined with cyclophosphamide plus vincristine compared with doxorubicin plus cyclophosphamide plus vincristine and with high-dose cyclophosphamide plus vincristine in the treatment of small-cell carcinoma of the lung: a randomized trial of the Bristol Lung Cancer Study Group. J Clin Oncol. 1989 Apr;7(4):450-6. link to original article dosing details in manuscript have been reviewed by our editors PubMed
CEV (Carboplatin/Etoposide)
CEV: Carboplatin, Etoposide, Vincristine
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Reck et al. 2003 | 1998-01 to 1999-12 | Phase 3 (C) | TEC | Seems to have inferior OS |
Note: cycle duration was not specified.
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 30 to 60 minutes once on day 1
- Etoposide (Vepesid) by the following stage-specific criteria:
- Stage I-IIIB: 159 mg/m2 IV over 30 minutes once per day on days 1 to 3
- Stage IV: 125 mg/m2 IV over 30 minutes once per day on days 1 to 3
- Vincristine (Oncovin) 2 mg IV once per day on days 1 & 8
2 or more cycles
References
- Reck M, von Pawel J, Macha HN, Kaukel E, Deppermann KM, Bonnet R, Ulm K, Hessler S, Gatzemeier U. Randomized phase III trial of paclitaxel, etoposide, and carboplatin versus carboplatin, etoposide, and vincristine in patients with small-cell lung cancer. J Natl Cancer Inst. 2003 Aug 6;95(15):1118-27. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Cisplatin & Etoposide (EP) & Pembrolizumab
EP & Pembrolizumab: Etoposide, Platinol (Cisplatin), Pembrolizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rudin et al. 2020 (KEYNOTE-604) | 2017-05-15 to 2018-07-30 | Phase 3 (E-esc) | 1a. CE 1b. EP |
Seems to have superior OS1 (co-primary endpoint) OS24: 22.5% vs 11.2% (HR 0.80, 95% CI 0.64-0.98) |
1This result did not meet the pre-specified threshold for statistical significance, and was the basis for withdrawal of the FDA indication.
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 to 4: 75 mg/m2 IV once on day 1
- Etoposide (Vepesid) as follows:
- Cycles 1 to 4: 100 mg/m2 IV once per day on days 1 to 3
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
References
- KEYNOTE-604: Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gümüş M, Kato T, Kalemkerian GP, Luo Y, Ebiana V, Pietanza MC, Kim HR; KEYNOTE-604 Investigators. Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. J Clin Oncol. 2020 Jul 20;38(21):2369-2379. Epub 2020 May 29. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT03066778
Cyclophosphamide & Lomustine
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ettinger & Lagakos 1982 | 1973-1977 | Phase 3 (C) | Cyclophosphamide, Lomustine, Procarbazine | Seems to have inferior ORR |
Chemotherapy
- Cyclophosphamide (Cytoxan) 700 mg/m2 IV once per day on days 1 & 22
- Lomustine (CCNU) 70 mg/m2 PO once on day 1
42-day cycles
References
- Ettinger DS, Lagakos S; ECOG. Phase III study of CCNU, cyclophosphamide, adriamycin, vincristine, and VP-16 in small-cell carcinoma of the lung. Cancer. 1982 Apr 15;49(8):1544-54. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Cyclophosphamide, Lomustine, Methotrexate
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cohen et al. 1979 | 1975-1977 | Phase 3 (C) | Chemotherapy & Thymosin fraction V | Seems to have inferior OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1500 mg/m2 IV once on day 1, then 1000 mg/m2 IV once on day 22
- Lomustine (CCNU) 100 mg/m2 PO once on day 1
- Methotrexate (MTX) 15 mg/m2 (route not specified) on days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32 (twice per week)
42-day course
References
- Cohen MH, Chretien PB, Ihde DC, Fossieck BE Jr, Makuch R, Bunn PA Jr, Johnston AV, Shackney SE, Matthews MJ, Lipson SD, Kenady DE, Minna JD. Thymosin fraction V and intensive combination chemotherapy: prolonging the survival of patients with small-cell lung cancer. JAMA. 1979 Apr 27;241(17):1813-5. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Cyclophosphamide, Lomustine, Procarbazine
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ettinger & Lagakos 1982 | 1973-1977 | Phase 3 (E-esc) | Cyclophosphamide & Lomustine | Seems to have superior ORR |
Chemotherapy
- Cyclophosphamide (Cytoxan) 700 mg/m2 IV once per day on days 1 & 22
- Lomustine (CCNU) 70 mg/m2 PO once on day 1
- Procarbazine (Matulane) 70 mg/m2 PO once per day on days 2 to 8, 22 to 28
42-day cycles
References
- Ettinger DS, Lagakos S; ECOG. Phase III study of CCNU, cyclophosphamide, adriamycin, vincristine, and VP-16 in small-cell carcinoma of the lung. Cancer. 1982 Apr 15;49(8):1544-54. link to original article dosing details in manuscript have been reviewed by our editors PubMed
EVI
EVI: Epirubicin, Vindesine, Ifosfamide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sculier et al. 2001 | 1993-2000 | Phase 3 (C) | 1. EVI & GM-CSF; accelerated | Did not meet primary endpoint of OS |
2. Accelerated EVI & antibiotics | Did not meet primary endpoint of OS |
Note: Not commonly used but was a comparator arm for at least one RCT; here for reference purposes only.
Chemotherapy
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Vindesine (Eldisine) 3 mg/m2 IV once on day 1
- Ifosfamide (Ifex) 5000 mg/m2 IV once on day 1
Supportive therapy
21-day cycle for 6 cycles
References
- Sculier JP, Paesmans M, Lecomte J, Van Cutsem O, Lafitte JJ, Berghmans T, Koumakis G, Florin MC, Thiriaux J, Michel J, Giner V, Berchier MC, Mommen P, Ninane V, Klastersky J; European Lung Cancer Working Party. A three-arm phase III randomised trial assessing, in patients with extensive-disease small-cell lung cancer, accelerated chemotherapy with support of haematological growth factor or oral antibiotics. Br J Cancer. 2001 Nov 16;85(10):1444-51. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
ICE
ICE: Ifosfamide, Carboplatin, Etoposide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lorigan et al. 2005 | 1994-2001 | Phase 3 (C) | Dose-dense ICE, then auto HSCT | Did not meet primary endpoint of OS |
Chemotherapy
- Ifosfamide (Ifex) 5000 mg/m2 IV continuous infusion over 24 hours, started on day 1
- Carboplatin (Paraplatin) 300 mg/m2 IV once on day 1
- Etoposide (Vepesid) 180 mg/m2 IV once per day on days 1 & 2
Supportive therapy
- Mesna (Mesnex) 5000 mg/m2 IV continuous infusion over 24 hours, started on day 1
28-day cycles
References
- Lorigan P, Woll PJ, O'Brien ME, Ashcroft LF, Sampson MR, Thatcher N. Randomized phase III trial of dose-dense chemotherapy supported by whole-blood hematopoietic progenitors in better-prognosis small-cell lung cancer. J Natl Cancer Inst. 2005 May 4;97(9):666-74. Erratum in: J Natl Cancer Inst. 2005 Jun 15;97(12):941. link to original article dosing details in manuscript have been reviewed by our editors PubMed
ICE-V
ICE-V: Ifosfamide, Carboplatin, Etoposide, Vincristine
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Thatcher et al. 2005 (MRC LU21) | 1996-03 to 2002-02 | Phase 3 (E-esc) | 1a. CDE 1b. EP |
Superior OS (primary endpoint) Median OS: 15.6 vs 11.6 mo (HR 0.74, 95% CI 0.60-0.91) |
Chemotherapy
- Ifosfamide (Ifex) 5000 mg/m2 IV once on day 1
- Carboplatin (Paraplatin) 300 mg/m2 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 1 & 2, then 240 mg/m2 PO once on day 3
- Vincristine (Oncovin) 1 mg/m2 IV once on day 14
Supportive therapy
28-day cycle for 6 cycles
References
- MRC LU21: Thatcher N, Qian W, Clark PI, Hopwood P, Sambrook RJ, Owens R, Stephens RJ, Girling DJ. Ifosfamide, carboplatin, and etoposide with midcycle vincristine versus standard chemotherapy in patients with small-cell lung cancer and good performance status: clinical and quality-of-life results of the British Medical Research Council multicenter randomized LU21 trial. J Clin Oncol. 2005 Nov 20;23(33):8371-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00002822
PCDE
PCDE: Platinol (Cisplatin), Cyclophosphamide, EpiDoxorubicin (Epirubicin), Etoposide
Regimen variant #1, lower-dose etoposide
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pujol et al. 1997 | 1991-1994 | Phase 3 (C) | PCDE; high-dose | Superior OS |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once on day 2
- Cyclophosphamide (Cytoxan) 400 mg/m2 IV once per day on days 1 to 3
- Epirubicin (Ellence) 40 mg/m2 IV once on day 1
- Etoposide (Vepesid) 75 mg/m2 IV once per day on days 1 to 3
28-day cycle for 6 cycles
Regimen variant #2, higher-dose etoposide
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pujol et al. 2001 (FNCLCC 95012) | 1996-1999 | Phase 3 (E-esc) | EP | Superior OS |
Pujol et al. 2007 (FNCLCC cleo04 IFCT 00-01) | 2000-2004 | Phase 3 (C) | PCDE & Thalidomide | Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once on day 2
- Cyclophosphamide (Cytoxan) 400 mg/m2 IV once per day on days 1 to 3
- Epirubicin (Ellence) 40 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
28-day cycle for 6 cycles
References
- Pujol JL, Douillard JY, Rivière A, Quoix E, Lagrange JL, Berthaud P, Bardonnet-Comte M, Polin V, Gautier V, Milleron B, Chomy F, Chomy P, Spaeth D, Le Chevalier T. Dose-intensity of a four-drug chemotherapy regimen with or without recombinant human granulocyte-macrophage colony-stimulating factor in extensive-stage small-cell lung cancer: a multicenter randomized phase III study. J Clin Oncol. 1997 May;15(5):2082-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- FNCLCC 95012: Pujol JL, Daurès JP, Rivière A, Quoix E, Westeel V, Quantin X, Breton JL, Lemarié E, Poudenx M, Milleron B, Moro D, Debieuvre D, Le Chevalier T. Etoposide plus cisplatin with or without the combination of 4'-epidoxorubicin plus cyclophosphamide in treatment of extensive small-cell lung cancer: a French Federation of Cancer Institutes multicenter phase III randomized study. J Natl Cancer Inst. 2001 Feb 21;93(4):300-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00003606
- FNCLCC cleo04/IFCT 00-01: Pujol JL, Breton JL, Gervais R, Tanguy ML, Quoix E, David P, Janicot H, Westeel V, Gameroff S, Genève J, Maraninchi D. Phase III double-blind, placebo-controlled study of thalidomide in extensive-disease small-cell lung cancer after response to chemotherapy: an intergroup study FNCLCC cleo04 IFCT 00-01. J Clin Oncol. 2007 Sep 1;25(25):3945-51. link to original article dosing details in manuscript have been reviewed by our editors PubMed
PCE
PCE: Paclitaxel, Carboplatin, Etoposide
TEC: Taxol (Paclitaxel) Etoposide), Carboplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Reck et al. 2003 | 1998-01 to 1999-12 | Phase 3 (E-switch-ic) | CEV | Seems to have superior OS |
Note: cycle duration was not specified.
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 4
- Carboplatin (Paraplatin) AUC 5 IV over 30 to 60 minutes once on day 4
- Etoposide (Vepesid) by the following stage-specific criteria:
- Stage I-IIIB: 125 mg/m2 IV over 30 minutes once per day on days 1 to 3
- Stage IV: 102.2 mg/m2 IV over 30 minutes once per day on days 1 to 3
2 or more cycles
References
- Reck M, von Pawel J, Macha HN, Kaukel E, Deppermann KM, Bonnet R, Ulm K, Hessler S, Gatzemeier U. Randomized phase III trial of paclitaxel, etoposide, and carboplatin versus carboplatin, etoposide, and vincristine in patients with small-cell lung cancer. J Natl Cancer Inst. 2003 Aug 6;95(15):1118-27. link to original article dosing details in manuscript have been reviewed by our editors PubMed
VIP
VIP: Vepesid (Etoposide), Ifosfamide, Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Loehrer et al. 1995 | 1989-1993 | Phase 3 (E-esc) | Cisplatin & Etoposide | Seems to have superior OS |
Chemotherapy
- Etoposide (Vepesid) 75 mg/m2 IV once per day on days 1 to 4
- Ifosfamide (Ifex) 1200 mg/m2 IV once per day on days 1 to 4
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 4
21-day cycle for 4 cycles
References
- Loehrer PJ Sr, Ansari R, Gonin R, Monaco F, Fisher W, Sandler A, Einhorn LH; Hoosier Oncology Group. Cisplatin plus etoposide with and without ifosfamide in extensive small-cell lung cancer: a Hoosier Oncology Group study. J Clin Oncol. 1995 Oct;13(10):2594-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
VMV-VAC
VMV-VAC: Vincristine, Methotrexate, VP-16 (Etoposide), followed by Vincristine, Adriamycin (Doxorubicin), Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Livingston et al. 1984 (SWOG S7828) | 1978-1980 | Phase 3 (E-esc) | 1. VAC 2. VMV |
Did not meet endpoint of OS |
Chemotherapy, VMV portion (cycles 1 & 2)
- Vincristine (Oncovin) 2 mg IV once per day on days 1, 8, 15
- Methotrexate (MTX) 50 mg/m2 IV once on day 1
- Etoposide (Vepesid) 60 mg/m2 IV once per day on days 1 to 5
Chemotherapy, VAC portion (cycles 3 & 4)
- Vincristine (Oncovin) 2 mg IV once per day on days 1, 8, 15
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
21-day cycle for 4 cycles (VMV x 2; VAC x 2)
References
- SWOG S7828: Livingston RB, Mira JG, Chen TT, McGavran M, Costanzi JJ, Samson M. Combined modality treatment of extensive small cell lung cancer: a Southwest Oncology Group study. J Clin Oncol. 1984 Jun;2(6):585-90. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Relapsed or refractory disease
CDE
CDE: Cyclophosphamide, Doxorubicin, Etoposide
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Postmus et al. 1987 | Not reported | Phase 2 |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1, 3, 5
21-day cycle for 5 cycles
References
- Postmus PE, Berendsen HH, van Zandwijk N, Splinter TA, Burghouts JT, Bakker W. Retreatment with the induction regimen in small cell lung cancer relapsing after an initial response to short term chemotherapy. Eur J Cancer Clin Oncol. 1987 Sep;23(9):1409-11. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Ipilimumab & Nivolumab
Regimen variant #1
Study | Dates of enrollment | Evidence |
---|---|---|
Antonia et al. 2016 (CheckMate 032SCLC) | 2013-2015 | Phase 1/2 (RT) |
Note: it is unclear which schedule of ipilimumab & nivolumab is preferred based on the abstract.
Immunotherapy
- Ipilimumab (Yervoy) as follows:
- Cycles 1 to 4: 1 mg/kg IV once on day 1
- Nivolumab (Opdivo) 3 mg/kg IV once on day 1
21-day cycle for 4 cycles, then 14-day cycles
Regimen variant #2
Study | Dates of enrollment | Evidence |
---|---|---|
Antonia et al. 2016 (CheckMate 032SCLC) | 2013-2015 | Phase 1/2 (RT) |
Note: it is unclear which schedule of ipilimumab & nivolumab is preferred based on the abstract.
Immunotherapy
- Ipilimumab (Yervoy) as follows:
- Cycles 1 to 4: 3 mg/kg IV once on day 1
- Nivolumab (Opdivo) as follows:
- Cycles 1 to 4: 1 mg/kg IV once on day 1
- Cycle 5 onwards: 3 mg/kg IV once on day 1
21-day cycle for 4 cycles, then 14-day cycles
References
- CheckMate 032SCLC: Antonia SJ, López-Martin JA, Bendell J, Ott PA, Taylor M, Eder JP, Jäger D, Pietanza MC, Le DT, de Braud F, Morse MA, Ascierto PA, Horn L, Amin A, Pillai RN, Evans J, Chau I, Bono P, Atmaca A, Sharma P, Harbison CT, Lin CS, Christensen O, Calvo E. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016 Jul;17(7):883-95. Epub 2016 Jun 4. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01928394
- Update: Ready NE, Ott PA, Hellmann MD, Zugazagoitia J, Hann CL, de Braud F, Antonia SJ, Ascierto PA, Moreno V, Atmaca A, Salvagni S, Taylor M, Amin A, Camidge DR, Horn L, Calvo E, Li A, Lin WH, Callahan MK, Spigel DR. Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer: Results From the CheckMate 032 Randomized Cohort. J Thorac Oncol. 2020 Mar;15(3):426-435. Epub 2019 Oct 17. link to original article PubMed
Nivolumab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Antonia et al. 2016 (CheckMate 032SCLC) | 2013-2015 | Phase 1/2 (RT) |
References
- CheckMate 032SCLC: Antonia SJ, López-Martin JA, Bendell J, Ott PA, Taylor M, Eder JP, Jäger D, Pietanza MC, Le DT, de Braud F, Morse MA, Ascierto PA, Horn L, Amin A, Pillai RN, Evans J, Chau I, Bono P, Atmaca A, Sharma P, Harbison CT, Lin CS, Christensen O, Calvo E. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016 Jul;17(7):883-95. Epub 2016 Jun 4. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01928394
- Update: Ready NE, Ott PA, Hellmann MD, Zugazagoitia J, Hann CL, de Braud F, Antonia SJ, Ascierto PA, Moreno V, Atmaca A, Salvagni S, Taylor M, Amin A, Camidge DR, Horn L, Calvo E, Li A, Lin WH, Callahan MK, Spigel DR. Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer: Results From the CheckMate 032 Randomized Cohort. J Thorac Oncol. 2020 Mar;15(3):426-435. Epub 2019 Oct 17. link to original article PubMed
Pembrolizumab monotherapy
Regimen variant #1, 10 mg/kg q2wk
Study | Dates of enrollment | Evidence |
---|---|---|
Ott et al. 2017c (KEYNOTE-028SCLC) | 2014-2015 | Phase 1b (RT) |
Immunotherapy
- Pembrolizumab (Keytruda) 10 mg/kg IV once on day 1
14-day cycle for up to 52 cycles (2 years)
Regimen variant #2, 200 mg q3wk
FDA-recommended dose |
Study | Evidence |
---|---|
Awaiting publication (KEYNOTE-158SCLC) | Phase 2 |
Note: this arm of KEYNOTE-158 has not been published yet, to our knowledge. KEYNOTE-158 was a basket study with multiple arms of different enrollment periods.
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
References
- KEYNOTE-028SCLC: Ott PA, Elez E, Hiret S, Kim DW, Morosky A, Saraf S, Piperdi B, Mehnert JM. Pembrolizumab in patients With extensive-stage small-cell lung cancer: results from the phase Ib KEYNOTE-028 study. J Clin Oncol. 2017 Dec 1;35(34):3823-3829. Epub 2017 Aug 16. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT02054806
- KEYNOTE-158SCLC: NCT02628067
Relapsed or refractory disease, second-line
Nivolumab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Spigel et al. 2021 (CheckMate 331) | 2015-2017 | Phase 3 (E-switch-ooc) | 1a. Amrubicin 1b. Topotecan |
Might have superior OS (primary endpoint) Median OS: 7.5 vs 8.4 mo (HR 0.86, 95% CI 0.72-1.04) |
References
- CheckMate 331: Spigel DR, Vicente D, Ciuleanu TE, Gettinger S, Peters S, Horn L, Audigier-Valette C, Pardo Aranda N, Juan-Vidal O, Cheng Y, Zhang H, Shi M, Luft A, Wolf J, Antonia S, Nakagawa K, Fairchild J, Baudelet C, Pandya D, Doshi P, Chang H, Reck M. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331. Ann Oncol. 2021 May;32(5):631-641. Epub 2021 Feb 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02481830