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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? See the [[Small_cell_lung_cancer|main SCLC page]] for current regimens. | The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? See the [[Small_cell_lung_cancer|main SCLC page]] for current regimens. | ||
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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> | ||
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{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
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=Limited stage, induction= | =Limited stage, induction= | ||
==CAV {{#subobject:10ggc3|Regimen=1}}== | ==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:#eeeeee"> | ||
===Regimen {{#subobject:4bb088|Variant=1}}=== | ===Regimen {{#subobject:4bb088|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
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|} | |} | ||
+ | <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 100 mg) IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> (maximum dose of 100 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 | ||
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'''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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8391064 PubMed] | ||
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==CAV/PE {{#subobject:106cc3|Regimen=1}}== | ==CAV/PE {{#subobject:106cc3|Regimen=1}}== | ||
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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:#eeeeee"> | ||
===Regimen {{#subobject:4bb088|Variant=1}}=== | ===Regimen {{#subobject:4bb088|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
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|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy, CAV portion==== | ====Chemotherapy, CAV portion==== | ||
*[[Cyclophosphamide (Cytoxan)]] as follows: | *[[Cyclophosphamide (Cytoxan)]] as follows: | ||
Line 67: | Line 64: | ||
*[[Vincristine (Oncovin)]] as follows: | *[[Vincristine (Oncovin)]] as follows: | ||
**Cycles 1, 3, 5: 2 mg IV once on day 1 | **Cycles 1, 3, 5: 2 mg IV once on day 1 | ||
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====Chemotherapy, PE portion==== | ====Chemotherapy, PE portion==== | ||
*[[Cisplatin (Platinol)]] as follows: | *[[Cisplatin (Platinol)]] as follows: | ||
Line 73: | Line 69: | ||
*[[Etoposide (Vepesid)]] as follows: | *[[Etoposide (Vepesid)]] as follows: | ||
**Cycles 2, 4, 6: 100 mg/m<sup>2</sup> IV over 40 to 60 minutes once on day 1 | **Cycles 2, 4, 6: 100 mg/m<sup>2</sup> IV over 40 to 60 minutes once on day 1 | ||
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'''21-day cycle for 6 cycles''' | '''21-day cycle for 6 cycles''' | ||
− | + | </div></div> | |
===References=== | ===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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/3040923 PubMed] | # 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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/3040923 PubMed] | ||
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==MACC {{#subobject:219cc3|Regimen=1}}== | ==MACC {{#subobject:219cc3|Regimen=1}}== | ||
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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:#eeeeee"> | ||
===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;" | ||
Line 97: | Line 91: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Methotrexate (MTX)]] | *[[Methotrexate (MTX)]] | ||
Line 102: | Line 97: | ||
*[[Cyclophosphamide (Cytoxan)]] | *[[Cyclophosphamide (Cytoxan)]] | ||
*[[Lomustine (CCNU)]] | *[[Lomustine (CCNU)]] | ||
− | + | </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] [https://pubmed.ncbi.nlm.nih.gov/2991478 PubMed] | ||
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==VMV-VAC {{#subobject:139cc3|Regimen=1}}== | ==VMV-VAC {{#subobject:139cc3|Regimen=1}}== | ||
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VMV-VAC: '''<u>V</u>'''incristine, '''<u>M</u>'''ethotrexate, '''<u>V</u>'''P-16 (Etoposide), '''<u>V</u>'''P-16 (Etoposide), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide | VMV-VAC: '''<u>V</u>'''incristine, '''<u>M</u>'''ethotrexate, '''<u>V</u>'''P-16 (Etoposide), '''<u>V</u>'''P-16 (Etoposide), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:4cc088|Variant=1}}=== | ===Regimen {{#subobject:4cc088|Variant=1}}=== | ||
{| class="wikitable" style="width: 40%; text-align:center;" | {| class="wikitable" style="width: 40%; text-align:center;" | ||
Line 118: | Line 112: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Vincristine (Oncovin)]] | *[[Vincristine (Oncovin)]] | ||
Line 124: | Line 119: | ||
*[[Doxorubicin (Adriamycin)]] | *[[Doxorubicin (Adriamycin)]] | ||
*[[Cyclophosphamide (Cytoxan)]] | *[[Cyclophosphamide (Cytoxan)]] | ||
− | + | </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] [https://pubmed.ncbi.nlm.nih.gov/3031226 PubMed] | ||
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=Limited stage, definitive chemoradiotherapy= | =Limited stage, definitive chemoradiotherapy= | ||
==CC/DE & RT {{#subobject:189bcc|Regimen=1}}== | ==CC/DE & RT {{#subobject:189bcc|Regimen=1}}== | ||
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CC/DE & RT: '''<u>C</u>'''yclophosphamide & '''<u>C</u>'''isplatin alternating with '''<u>D</u>'''oxorubicin & '''<u>E</u>'''toposide, with '''<u>R</u>'''adiation '''<u>T</u>'''herapy | CC/DE & RT: '''<u>C</u>'''yclophosphamide & '''<u>C</u>'''isplatin alternating with '''<u>D</u>'''oxorubicin & '''<u>E</u>'''toposide, with '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===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;" | ||
Line 147: | Line 141: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] | *[[Cyclophosphamide (Cytoxan)]] | ||
Line 154: | Line 149: | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
*[[External beam radiotherapy]] | *[[External beam radiotherapy]] | ||
− | + | </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://doi.org/10.1056/NEJM199312163292504 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8247036 PubMed] | # 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] [https://pubmed.ncbi.nlm.nih.gov/8247036 PubMed] | ||
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==CAV & RT {{#subobject:a37yf8|Regimen=1}}== | ==CAV & RT {{#subobject:a37yf8|Regimen=1}}== | ||
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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:#eeeeee"> | ||
===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;" | ||
Line 189: | Line 183: | ||
|} | |} | ||
''<sup>1</sup>It is not clear from the manuscript what the primary endpont of the study was.'' | ''<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)]] | ||
Line 195: | Line 190: | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
*Concurrent [[External_beam_radiotherapy|radiation therapy]] | *Concurrent [[External_beam_radiotherapy|radiation therapy]] | ||
− | + | </div></div> | |
===References=== | ===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. [https://doi.org/10.1200/jco.1984.2.11.1200 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6092555/ 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] | # 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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8391064 PubMed] | ||
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==CEV & RT {{#subobject:a3e998|Regimen=1}}== | ==CEV & RT {{#subobject:a3e998|Regimen=1}}== | ||
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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:#eeeeee"> | ||
===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;" | ||
Line 228: | Line 222: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] | *[[Cyclophosphamide (Cytoxan)]] | ||
Line 234: | Line 229: | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
*Concurrent [[External_beam_radiotherapy|radiation therapy]] | *Concurrent [[External_beam_radiotherapy|radiation therapy]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
*Patients with CR: [[Small_cell_lung_cancer#Whole_brain_irradiation|Prophylactic cranial irradiation]] | *Patients with CR: [[Small_cell_lung_cancer#Whole_brain_irradiation|Prophylactic 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://doi.org/10.1056/NEJM198704093161504 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3029592 PubMed] | # '''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12488411 PubMed] | # Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. [https://doi.org/10.1200/jco.2002.12.111 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12488411 PubMed] | ||
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==Methotrexate, RT, Cyclophosphamide {{#subobject:a4e998|Regimen=1}}== | ==Methotrexate, RT, Cyclophosphamide {{#subobject:a4e998|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Protocol {{#subobject:78c1d9|Variant=1}}=== | ===Protocol {{#subobject:78c1d9|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 253: | Line 250: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy, part 1==== | ====Chemotherapy, part 1==== | ||
*[[Methotrexate (MTX)]] | *[[Methotrexate (MTX)]] | ||
Line 259: | Line 257: | ||
====Chemotherapy, part 2==== | ====Chemotherapy, part 2==== | ||
*[[Cyclophosphamide (Cytoxan)]] | *[[Cyclophosphamide (Cytoxan)]] | ||
+ | </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] | # 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] | ||
− | |||
=Extensive stage, induction= | =Extensive stage, induction= | ||
==ACE {{#subobject:9fbf31|Regimen=1}}== | ==ACE {{#subobject:9fbf31|Regimen=1}}== | ||
− | |||
ACE: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide | 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>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 | <br>CAE: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>E</u>'''toposide | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:949381|Variant=1}}=== | ===Regimen {{#subobject:949381|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 295: | Line 293: | ||
|- | |- | ||
|} | |} | ||
− | ''Used as a comparator arm in older studies. The non-randomized results of Klastersky et al. 1985 established this regimen as a standard control.'' | + | ''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==== | ====Chemotherapy==== | ||
*[[Doxorubicin (Adriamycin)]] | *[[Doxorubicin (Adriamycin)]] | ||
*[[Cyclophosphamide (Cytoxan)]] | *[[Cyclophosphamide (Cytoxan)]] | ||
*[[Etoposide (Vepesid)]] | *[[Etoposide (Vepesid)]] | ||
− | + | </div></div> | |
===References=== | ===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. [https://doi.org/10.1002/1097-0142%2819850701%2956%3A1%3C71%3A%3AAID-CNCR2820560112%3E3.0.CO%3B2-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2988738 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] [https://pubmed.ncbi.nlm.nih.gov/2988738 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] [https://pubmed.ncbi.nlm.nih.gov/8410110 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] [https://pubmed.ncbi.nlm.nih.gov/8410110 PubMed] | ||
# Baka S, Califano R, Ferraldeschi R, Aschroft L, Thatcher N, Taylor P, Faivre-Finn C, Blackhall F, Lorigan P. Phase III randomised trial of doxorubicin-based chemotherapy compared with platinum-based chemotherapy in small-cell lung cancer. Br J Cancer. 2008 Aug 5;99(3):442-7. [https://doi.org/10.1038/sj.bjc.6604480 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527803/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18665190 PubMed] | # Baka S, Califano R, Ferraldeschi R, Aschroft L, Thatcher N, Taylor P, Faivre-Finn C, Blackhall F, Lorigan P. Phase III randomised trial of doxorubicin-based chemotherapy compared with platinum-based chemotherapy in small-cell lung cancer. Br J Cancer. 2008 Aug 5;99(3):442-7. [https://doi.org/10.1038/sj.bjc.6604480 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527803/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18665190 PubMed] | ||
− | |||
==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:#eeeeee"> | ||
===Regimen {{#subobject:e3138e|Variant=1}}=== | ===Regimen {{#subobject:e3138e|Variant=1}}=== | ||
{| class="wikitable" style="width: 40%; text-align:center;" | {| class="wikitable" style="width: 40%; text-align:center;" | ||
Line 318: | Line 316: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Bleomycin (Blenoxane)]] | *[[Bleomycin (Blenoxane)]] | ||
Line 323: | Line 322: | ||
*[[Cyclophosphamide (Cytoxan)]] | *[[Cyclophosphamide (Cytoxan)]] | ||
*[[Vincristine (Oncovin)]] | *[[Vincristine (Oncovin)]] | ||
+ | </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://doi.org/10.1001/jama.1976.03260380019019 link to original article] [https://pubmed.ncbi.nlm.nih.gov/55504 PubMed] | # 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] [https://pubmed.ncbi.nlm.nih.gov/55504 PubMed] | ||
− | |||
==Carboplatin & Etoposide (CE) & Pembrolizumab {{#subobject:o9ga26|Regimen=1}}== | ==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:#eeeeee"> | ||
===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;" | ||
Line 345: | Line 344: | ||
|} | |} | ||
''<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.'' | ''<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 352: | Line 352: | ||
====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] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32468956/ PubMed] NCT03066778 | # '''KEYNOTE-604:''' Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gümüş M, Kato T, Kalemkerian GP, Luo Y, Ebiana V, Pietanza MC, Kim HR; KEYNOTE-604 Investigators. Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. J Clin Oncol. 2020 Jul 20;38(21):2369-2379. Epub 2020 May 29. [https://doi.org/10.1200/jco.20.00793 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32468956/ PubMed] NCT03066778 | ||
− | |||
==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:#eeeeee"> | ||
===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;" | ||
Line 386: | Line 385: | ||
|} | |} | ||
''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:#eeeeee"> | ||
===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;" | ||
Line 428: | Line 428: | ||
|- | |- | ||
|} | |} | ||
+ | <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|PCI]] | *ECOG E1588, CR: [[#CAV_2|CAV]] x 2 (6 to 8 total), then [[#Whole_brain_irradiation_2|PCI]] | ||
*ECOG E1588, PR: [[#CAV_2|CAV]] until progression of disease, then salvage [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]] | *ECOG E1588, PR: [[#CAV_2|CAV]] until progression of disease, then salvage [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]] | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 1000/50/2, flat-dose vincristine {{#subobject:3dc31b|Variant=1}}=== | ===Regimen variant #3, 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;" | ||
Line 469: | Line 472: | ||
|- | |- | ||
|} | |} | ||
+ | <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://jamanetwork.com/journals/jama/article-abstract/352016 link to original article] [https://pubmed.ncbi.nlm.nih.gov/190427 PubMed] | # 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://jamanetwork.com/journals/jama/article-abstract/352016 link to original article] [https://pubmed.ncbi.nlm.nih.gov/190427 PubMed] | ||
Line 485: | Line 488: | ||
# 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] | # 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. [https://doi.org/10.1016/s0169-5002(02)00074-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12234701 PubMed] | # '''ECOG E1588:''' Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; [[Study_Groups#ECOG|ECOG]]. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. [https://doi.org/10.1016/s0169-5002(02)00074-0 link to original article] '''contains dosing details in manuscript''' [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:#eeeeee"> | ||
===Protocol {{#subobject:2a8dee|Variant=1}}=== | ===Protocol {{#subobject:2a8dee|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 528: | Line 530: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy, CAV portion==== | ====Chemotherapy, CAV portion==== | ||
*[[Cyclophosphamide (Cytoxan)]] | *[[Cyclophosphamide (Cytoxan)]] | ||
*[[Doxorubicin (Adriamycin)]] | *[[Doxorubicin (Adriamycin)]] | ||
*[[Vincristine (Oncovin)]] | *[[Vincristine (Oncovin)]] | ||
− | |||
====Chemotherapy, PE portion==== | ====Chemotherapy, PE portion==== | ||
*[[Cisplatin (Platinol)]] | *[[Cisplatin (Platinol)]] | ||
*[[Etoposide (Vepesid)]] | *[[Etoposide (Vepesid)]] | ||
− | + | </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. [https://doi.org/10.7326/0003-4819-107-4-451 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2820289 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. [https://doi.org/10.7326/0003-4819-107-4-451 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2820289 PubMed] | ||
Line 543: | Line 545: | ||
# '''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] [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 | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===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;" | ||
Line 570: | Line 571: | ||
|} | |} | ||
''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.'' | ''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)]] | ||
Line 575: | Line 577: | ||
*[[Vincristine (Oncovin)]] | *[[Vincristine (Oncovin)]] | ||
*[[Etoposide (Vepesid)]] | *[[Etoposide (Vepesid)]] | ||
− | + | </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] [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://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] | # 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}}== | ||
− | |||
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 | ||
<br>CAE: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>E</u>'''toposide | <br>CAE: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>E</u>'''toposide | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:be62e9|Variant=1}}=== | ===Regimen {{#subobject:be62e9|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 617: | Line 618: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] | *[[Cyclophosphamide (Cytoxan)]] | ||
*[[Doxorubicin (Adriamycin)]] | *[[Doxorubicin (Adriamycin)]] | ||
*[[Etoposide (Vepesid)]] | *[[Etoposide (Vepesid)]] | ||
− | + | </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] | # 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] | ||
Line 627: | Line 629: | ||
# '''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] | # '''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] | ||
# '''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] [https://pubmed.ncbi.nlm.nih.gov/17826977 PubMed] NCT00003696 | # '''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] [https://pubmed.ncbi.nlm.nih.gov/17826977 PubMed] NCT00003696 | ||
− | |||
==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:#eeeeee"> | ||
===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;" | ||
Line 646: | Line 647: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] | *[[Cyclophosphamide (Cytoxan)]] | ||
*[[Epirubicin (Ellence)]] | *[[Epirubicin (Ellence)]] | ||
*[[Vincristine (Oncovin)]] | *[[Vincristine (Oncovin)]] | ||
− | + | </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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12488411 PubMed] | # Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. [https://doi.org/10.1200/jco.2002.12.111 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12488411 PubMed] | ||
− | |||
==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:#eeeeee"> | ||
===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;" | ||
Line 672: | Line 673: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] | *[[Cyclophosphamide (Cytoxan)]] | ||
*[[Etoposide (Vepesid)]] | *[[Etoposide (Vepesid)]] | ||
*[[Vincristine (Oncovin)]] | *[[Vincristine (Oncovin)]] | ||
− | + | </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] [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:#eeeeee"> | ||
===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;" | ||
Line 698: | Line 699: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carboplatin (Paraplatin)]] | *[[Carboplatin (Paraplatin)]] | ||
*[[Etoposide (Vepesid)]] | *[[Etoposide (Vepesid)]] | ||
*[[Vincristine (Oncovin)]] | *[[Vincristine (Oncovin)]] | ||
− | + | </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://academic.oup.com/jnci/article/95/15/1118/2520358 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12902441 PubMed] | # 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://academic.oup.com/jnci/article/95/15/1118/2520358 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12902441 PubMed] | ||
− | |||
==Cisplatin & Etoposide (EP) & Pembrolizumab {{#subobject:eeja26|Regimen=1}}== | ==Cisplatin & Etoposide (EP) & Pembrolizumab {{#subobject:eeja26|Regimen=1}}== | ||
− | |||
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:#eeeeee"> | ||
===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;" | ||
Line 725: | Line 726: | ||
|} | |} | ||
''<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.'' | ''<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 732: | Line 734: | ||
====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] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32468956/ PubMed] NCT03066778 | # '''KEYNOTE-604:''' Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gümüş M, Kato T, Kalemkerian GP, Luo Y, Ebiana V, Pietanza MC, Kim HR; KEYNOTE-604 Investigators. Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. J Clin Oncol. 2020 Jul 20;38(21):2369-2379. Epub 2020 May 29. [https://doi.org/10.1200/jco.20.00793 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32468956/ PubMed] NCT03066778 | ||
− | |||
==Cyclophosphamide & Lomustine {{#subobject:ab365b|Regimen=1}}== | ==Cyclophosphamide & Lomustine {{#subobject:ab365b|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===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;" | ||
Line 754: | Line 755: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] | *[[Cyclophosphamide (Cytoxan)]] | ||
*[[Lomustine (CCNU)]] | *[[Lomustine (CCNU)]] | ||
− | + | </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] [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:#eeeeee"> | |
===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;" | ||
Line 778: | Line 779: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] | *[[Cyclophosphamide (Cytoxan)]] | ||
*[[Lomustine (CCNU)]] | *[[Lomustine (CCNU)]] | ||
*[[Methotrexate (MTX)]] | *[[Methotrexate (MTX)]] | ||
− | + | </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://jamanetwork.com/journals/jama/fullarticle/364557 link to original article] [https://pubmed.ncbi.nlm.nih.gov/219267 PubMed] | # 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://jamanetwork.com/journals/jama/fullarticle/364557 link to original article] [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:#eeeeee"> | |
===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;" | ||
Line 803: | Line 804: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] | *[[Cyclophosphamide (Cytoxan)]] | ||
*[[Lomustine (CCNU)]] | *[[Lomustine (CCNU)]] | ||
*[[Procarbazine (Matulane)]] | *[[Procarbazine (Matulane)]] | ||
+ | </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] [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:#eeeeee"> | ||
===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;" | ||
Line 831: | Line 833: | ||
|- | |- | ||
|} | |} | ||
− | ''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)]] | ||
*[[Vindesine (Eldisine)]] | *[[Vindesine (Eldisine)]] | ||
*[[Ifosfamide (Ifex)]] | *[[Ifosfamide (Ifex)]] | ||
− | + | </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://doi.org/10.1054/bjoc.2001.2114 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363948/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/11720426 PubMed] | # 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] [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:#eeeeee"> | ||
===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;" | ||
Line 858: | Line 860: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Ifosfamide (Ifex)]] | *[[Ifosfamide (Ifex)]] | ||
*[[Carboplatin (Paraplatin)]] | *[[Carboplatin (Paraplatin)]] | ||
*[[Etoposide (Vepesid)]] | *[[Etoposide (Vepesid)]] | ||
− | + | </div></div> | |
===References=== | ===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://academic.oup.com/jnci/article/97/9/666/2544232 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15870437 PubMed] | # 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://academic.oup.com/jnci/article/97/9/666/2544232 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15870437 PubMed] | ||
− | |||
==ICE-V {{#subobject:f5jbc2|Regimen=1}}== | ==ICE-V {{#subobject:f5jbc2|Regimen=1}}== | ||
− | |||
ICE-V: '''<u>I</u>'''fosfamide, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide, '''<u>V</u>'''incristine | ICE-V: '''<u>I</u>'''fosfamide, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide, '''<u>V</u>'''incristine | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:tr4a1b|Variant=1}}=== | ===Regimen {{#subobject:tr4a1b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 884: | Line 886: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Ifosfamide (Ifex)]] | *[[Ifosfamide (Ifex)]] | ||
Line 889: | Line 892: | ||
*[[Etoposide (Vepesid)]] | *[[Etoposide (Vepesid)]] | ||
*[[Vincristine (Oncovin)]] | *[[Vincristine (Oncovin)]] | ||
+ | </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] [https://pubmed.ncbi.nlm.nih.gov/16293867/ PubMed] NCT00002822 | #'''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] [https://pubmed.ncbi.nlm.nih.gov/16293867/ PubMed] 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 | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:bc58e8|Variant=1}}=== | ===Regimen {{#subobject:bc58e8|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 922: | Line 925: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cisplatin (Platinol)]] | *[[Cisplatin (Platinol)]] | ||
Line 927: | Line 931: | ||
*[[Epirubicin (Ellence)]] | *[[Epirubicin (Ellence)]] | ||
*[[Etoposide (Vepesid)]] | *[[Etoposide (Vepesid)]] | ||
− | + | </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] [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://academic.oup.com/jnci/article/93/4/300/2906465 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11181777 PubMed] NCT00003606 | # '''FNCLCC 95012:''' Pujol JL, Daurès JP, Rivière A, Quoix E, Westeel V, Quantin X, Breton JL, Lemarié E, Poudenx M, Milleron B, Moro D, Debieuvre D, Le Chevalier T. Etoposide plus cisplatin with or without the combination of 4'-epidoxorubicin plus cyclophosphamide in treatment of extensive small-cell lung cancer: a French Federation of Cancer Institutes multicenter phase III randomized study. J Natl Cancer Inst. 2001 Feb 21;93(4):300-8. [https://academic.oup.com/jnci/article/93/4/300/2906465 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11181777 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. [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] [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:#eeeeee"> | ||
===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;" | ||
Line 952: | Line 955: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Paclitaxel (Taxol)]] | *[[Paclitaxel (Taxol)]] | ||
*[[Carboplatin (Paraplatin)]] | *[[Carboplatin (Paraplatin)]] | ||
*[[Etoposide (Vepesid)]] | *[[Etoposide (Vepesid)]] | ||
− | + | </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://academic.oup.com/jnci/article/95/15/1118/2520358 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12902441 PubMed] | # 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://academic.oup.com/jnci/article/95/15/1118/2520358 link to original article] [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:#eeeeee"> | ||
===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;" | ||
Line 978: | Line 981: | ||
|- | |- | ||
|} | |} | ||
+ | <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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7595712 PubMed] | # Loehrer PJ Sr, Ansari R, Gonin R, Monaco F, Fisher W, Sandler A, Einhorn LH; Hoosier Oncology Group. Cisplatin plus etoposide with and without ifosfamide in extensive small-cell lung cancer: a Hoosier Oncology Group study. J Clin Oncol. 1995 Oct;13(10):2594-9. [https://doi.org/10.1200/JCO.1995.13.10.2594 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7595712 PubMed] | ||
− | |||
==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), '''<u>V</u>'''P-16 (Etoposide), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide | VMV-VAC: '''<u>V</u>'''incristine, '''<u>M</u>'''ethotrexate, '''<u>V</u>'''P-16 (Etoposide), '''<u>V</u>'''P-16 (Etoposide), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===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;" | ||
Line 1,006: | Line 1,008: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Vincristine (Oncovin)]] | *[[Vincristine (Oncovin)]] | ||
Line 1,012: | Line 1,015: | ||
*[[Doxorubicin (Adriamycin)]] | *[[Doxorubicin (Adriamycin)]] | ||
*[[Cyclophosphamide (Cytoxan)]] | *[[Cyclophosphamide (Cytoxan)]] | ||
− | + | </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] [https://pubmed.ncbi.nlm.nih.gov/6327927 PubMed] | ||
− | |||
=Relapsed or refractory disease= | =Relapsed or refractory disease= | ||
==CAV {{#subobject:d3d3e|Regimen=1}}== | ==CAV {{#subobject:d3d3e|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:#eeeeee"> | ||
===Regimen variant #1, no capping {{#subobject:1ugcbf|Variant=1}}=== | ===Regimen variant #1, no capping {{#subobject:1ugcbf|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,034: | Line 1,037: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1 | *[[Vincristine (Oncovin)]] 2 mg IV once on day 1 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, capped {{#subobject:83cdbf|Variant=1}}=== | ===Regimen variant #2, capped {{#subobject:83cdbf|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,056: | Line 1,060: | ||
|- | |- | ||
|} | |} | ||
− | ''von Pawel et al. 1999 does not clearly state the duration of each cycle, but 21 days is used in other CAV regimens, and there was no information in the paper that contradicted this.'' | + | ''Note: von Pawel et al. 1999 does not clearly state the duration of each cycle, but 21 days is used in other CAV regimens, and there was no information in the paper that contradicted this.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> (maximum dose of 2000 mg) (route not specified) once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> (maximum dose of 2000 mg) (route not specified) once on day 1 | ||
Line 1,063: | Line 1,068: | ||
====Supportive therapy==== | ====Supportive therapy==== | ||
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] use per physician discretion | *[[:Category:Granulocyte colony-stimulating factors|G-CSF]] use per physician discretion | ||
− | |||
'''21-day cycle for up to 6 cycles beyond maximal response''' | '''21-day cycle for up to 6 cycles beyond maximal response''' | ||
− | |||
''Patients with stable disease after 4 cycles could have treatment discontinued at physician discretion.'' | ''Patients with stable disease after 4 cycles could have treatment discontinued at physician discretion.'' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3 {{#subobject:531cce|Variant=1}}=== | ===Regimen variant #3 {{#subobject:531cce|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 1,080: | Line 1,084: | ||
|} | |} | ||
''Note: Ihde et al. 1994 did not specifically say that the three medications were all given on day 1, but this is assumed to be the case based on other CAV regimens.'' | ''Note: Ihde et al. 1994 did not specifically say that the three medications were all given on day 1, but this is assumed to be the case based on other CAV regimens.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
*[[#Cisplatin_.26_Etoposide_.28EP.29_2|EP]]; standard-dose versus [[#Cisplatin_.26_Etoposide_.28EP.29|EP]]; high-dose, with progression | *[[#Cisplatin_.26_Etoposide_.28EP.29_2|EP]]; standard-dose versus [[#Cisplatin_.26_Etoposide_.28EP.29|EP]]; high-dose, with progression | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 | ||
− | |||
'''21-day cycle for 4 cycles''' | '''21-day cycle for 4 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
# Ihde DC, Mulshine JL, Kramer BS, Steinberg SM, Linnoila RI, Gazdar AF, Edison M, Phelps RM, Lesar M, Phares JC, Grayson J, Minna JD, Johnson BE. Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. J Clin Oncol. 1994 Oct;12(10):2022-34. [https://doi.org/10.1200/jco.1994.12.10.2022 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7931470 PubMed] | # Ihde DC, Mulshine JL, Kramer BS, Steinberg SM, Linnoila RI, Gazdar AF, Edison M, Phelps RM, Lesar M, Phares JC, Grayson J, Minna JD, Johnson BE. Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. J Clin Oncol. 1994 Oct;12(10):2022-34. [https://doi.org/10.1200/jco.1994.12.10.2022 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7931470 PubMed] | ||
# von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, Stewart DJ, Clark PI, Palmer MC, Depierre A, Carmichael J, Krebs JB, Ross G, Lane SR, Gralla R. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999 Feb;17(2):658-67. [https://doi.org/10.1200/jco.1999.17.2.658 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10080612 PubMed] | # von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, Stewart DJ, Clark PI, Palmer MC, Depierre A, Carmichael J, Krebs JB, Ross G, Lane SR, Gralla R. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999 Feb;17(2):658-67. [https://doi.org/10.1200/jco.1999.17.2.658 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10080612 PubMed] | ||
#'''ATLANTIS:''' Aix SP, Ciuleanu TE, Navarro A, Cousin S, Bonanno L, Smit EF, Chiappori A, Olmedo ME, Horvath I, Grohé C, Farago AF, López-Vilariño JA, Cullell-Young M, Nieto A, Vasco N, Gómez J, Kahatt C, Zeaiter A, Carcereny E, Roubec J, Syrigos K, Lo G, Barneto I, Pope A, Sánchez A, Kattan J, Zarogoulidis K, Waller CF, Bischoff H, Juan-Vidal O, Reinmuth N, Dómine M, Paz-Ares L. Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial. Lancet Respir Med. 2023 Jan;11(1):74-86. Epub 2022 Oct 14. [https://doi.org/10.1016/s2213-2600(22)00309-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/36252599/ PubMed] NCT02566993 | #'''ATLANTIS:''' Aix SP, Ciuleanu TE, Navarro A, Cousin S, Bonanno L, Smit EF, Chiappori A, Olmedo ME, Horvath I, Grohé C, Farago AF, López-Vilariño JA, Cullell-Young M, Nieto A, Vasco N, Gómez J, Kahatt C, Zeaiter A, Carcereny E, Roubec J, Syrigos K, Lo G, Barneto I, Pope A, Sánchez A, Kattan J, Zarogoulidis K, Waller CF, Bischoff H, Juan-Vidal O, Reinmuth N, Dómine M, Paz-Ares L. Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial. Lancet Respir Med. 2023 Jan;11(1):74-86. Epub 2022 Oct 14. [https://doi.org/10.1016/s2213-2600(22)00309-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/36252599/ PubMed] NCT02566993 | ||
− | |||
==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:#eeeeee"> | ||
===Regimen {{#subobject:65860f|Variant=1}}=== | ===Regimen {{#subobject:65860f|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 1,108: | Line 1,113: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 3, 5 | ||
− | |||
'''21-day cycle for 5 cycles''' | '''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] '''contains dosing details in manuscript''' [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] '''contains dosing details in manuscript''' [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:#eeeeee"> | |
===Regimen variant #1 {{#subobject:aa43c1|Variant=1}}=== | ===Regimen variant #1 {{#subobject:aa43c1|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 1,132: | Line 1,136: | ||
|} | |} | ||
''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)]] as follows: | *[[Ipilimumab (Yervoy)]] as follows: | ||
**Cycles 1 to 4: 1 mg/kg IV once on day 1 | **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, then 14-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2 {{#subobject:b6a1ee|Variant=1}}=== | ===Regimen variant #2 {{#subobject:b6a1ee|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 1,151: | Line 1,156: | ||
|} | |} | ||
''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)]] as follows: | *[[Ipilimumab (Yervoy)]] as follows: | ||
Line 1,157: | Line 1,163: | ||
**Cycles 1 to 4: 1 mg/kg IV once on day 1 | **Cycles 1 to 4: 1 mg/kg IV once on day 1 | ||
**Cycle 5 onwards: 3 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''' | '''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://doi.org/10.1016/S1470-2045(16)30098-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27269741 PubMed] NCT01928394 | # '''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://doi.org/10.1016/S1470-2045(16)30098-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27269741 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. [https://doi.org/10.1016/j.jtho.2019.10.004 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31629915/ PubMed] | ##'''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:#eeeeee"> | |
===Regimen variant #1, weight-based {{#subobject:5a9324|Variant=1}}=== | ===Regimen variant #1, weight-based {{#subobject:5a9324|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 1,177: | Line 1,181: | ||
|- | |- | ||
|} | |} | ||
+ | <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><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, flat dose {{#subobject:5a8guac|Variant=1}}=== | ===Regimen variant #2, flat dose {{#subobject:5a8guac|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 1,197: | Line 1,202: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
*[[Nivolumab (Opdivo)]] 240 mg IV over 30 minutes once on day 1 | *[[Nivolumab (Opdivo)]] 240 mg IV over 30 minutes 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://doi.org/10.1016/S1470-2045(16)30098-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27269741 PubMed] NCT01928394 | # '''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://doi.org/10.1016/S1470-2045(16)30098-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27269741 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. [https://doi.org/10.1016/j.jtho.2019.10.004 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31629915/ PubMed] | ##'''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] | ||
# '''CheckMate 331:''' Spigel DR, Vicente D, Ciuleanu TE, Gettinger S, Peters S, Horn L, Audigier-Valette C, Pardo Aranda N, Juan-Vidal O, Cheng Y, Zhang H, Shi M, Luft A, Wolf J, Antonia S, Nakagawa K, Fairchild J, Baudelet C, Pandya D, Doshi P, Chang H, Reck M. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331. Ann Oncol. 2021 May;32(5):631-641. Epub 2021 Feb 1. [https://doi.org/10.1016/j.annonc.2021.01.071 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33539946/ PubMed] NCT02481830 | # '''CheckMate 331:''' Spigel DR, Vicente D, Ciuleanu TE, Gettinger S, Peters S, Horn L, Audigier-Valette C, Pardo Aranda N, Juan-Vidal O, Cheng Y, Zhang H, Shi M, Luft A, Wolf J, Antonia S, Nakagawa K, Fairchild J, Baudelet C, Pandya D, Doshi P, Chang H, Reck M. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331. Ann Oncol. 2021 May;32(5):631-641. Epub 2021 Feb 1. [https://doi.org/10.1016/j.annonc.2021.01.071 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33539946/ PubMed] NCT02481830 | ||
− | |||
==Pembrolizumab monotherapy {{#subobject:bc1cf4|Regimen=1}}== | ==Pembrolizumab monotherapy {{#subobject:bc1cf4|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1, 10 mg/kg q2wk {{#subobject:96a1cg|Variant=1}}=== | ===Regimen variant #1, 10 mg/kg q2wk {{#subobject:96a1cg|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 1,220: | Line 1,224: | ||
|- | |- | ||
|} | |} | ||
+ | <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:#eeeeee"> | ||
===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 1,239: | Line 1,244: | ||
|} | |} | ||
''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.'' | ||
+ | <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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28813164 PubMed] NCT02054806 | # '''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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28813164 PubMed] NCT02054806 | ||
# '''KEYNOTE-158:''' NCT02628067 | # '''KEYNOTE-158:''' NCT02628067 | ||
− | |||
[[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]] |
Revision as of 14:13, 28 December 2022
The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the NCCN Guidelines. Is there a regimen missing from this list? See the main SCLC page for current regimens.
31 regimens on this page
38 variants on this page
|
Limited stage, induction
CAV
CAV: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine
Regimen
Study | Years 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</sup (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 contains dosing details in manuscript PubMed
CAV/PE
CAV/PE: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine alternating with Platinol (Cisplatin) & Etoposide
Regimen
Study | Years 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
- Cyclophosphamide (Cytoxan) as follows:
- Cycles 1, 3, 5: 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) as follows:
- Cycles 1, 3, 5: 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) as follows:
- Cycles 1, 3, 5: 2 mg IV once on day 1
Chemotherapy, PE portion
- Cisplatin (Platinol) as follows:
- Cycles 2, 4, 6: 25 mg/m2 IV once on day 1
- Etoposide (Vepesid) as follows:
- Cycles 2, 4, 6: 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 contains dosing details in manuscript PubMed
MACC
MACC: Methotrexate, Adriamycin (Doxorubicin), Cyclophosphamide, CCNU (Lomustine)
Regimen
Study | Years 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 |
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 PubMed
VMV-VAC
VMV-VAC: Vincristine, Methotrexate, VP-16 (Etoposide), VP-16 (Etoposide), Adriamycin (Doxorubicin), Cyclophosphamide
Regimen
Study | Evidence |
---|---|
Kies et al. 1987 | Non-randomized portion of RCT |
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 PubMed
Limited stage, definitive chemoradiotherapy
CC/DE & RT
CC/DE & RT: Cyclophosphamide & Cisplatin alternating with Doxorubicin & Etoposide, with Radiation Therapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Arriagada et al. 1993 | 1988-1991 | Phase 3 (E-esc) | CC/DE & RT; lower-dose | Seems to have superior OS |
Chemotherapy
Radiotherapy
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 PubMed
CAV & RT
CAV & RT: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine, Radiation Therapy
Regimen
Study | Years 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.
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 contains dosing details in manuscript PubMed
CEV & RT
CEV & RT: Cyclophosphamide, Epirubicin, Vincristine, Radiation Therapy
Regimen
Study | Years 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 |
Subsequent treatment
- 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 contains dosing details in manuscript PubMed
Methotrexate, RT, Cyclophosphamide
Protocol
Study | Years of enrollment | Evidence |
---|---|---|
Thatcher et al. 1982 | 1978-1981 | Non-randomized portion of RCT |
Chemotherapy, part 1
Radiotherapy
Chemotherapy, part 2
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. link to original article PubMed
Extensive stage, induction
ACE
ACE: Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide
AVE: Adriamycin (Doxorubicin), Vepesid (Etoposide), Endoxan (Cyclophosphamide)
CAE: Cyclophosphamide, Adriamycin (Doxorubicin), Etoposide
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Klastersky et al. 1985 | NR | Phase 2 | ORR: 66% | |
Sculier et al. 1993 | 1987-NR | Phase 3 (C) | Multi-drug regimen | Did not meet primary endpoint of OS |
Baka et al. 2008 | 1999-2005 | Phase 3 (C) | EP | Did not meet primary endpoint of OS12 |
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.
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 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 PubMed
- Baka S, Califano R, Ferraldeschi R, Aschroft L, Thatcher N, Taylor P, Faivre-Finn C, Blackhall F, Lorigan P. Phase III randomised trial of doxorubicin-based chemotherapy compared with platinum-based chemotherapy in small-cell lung cancer. Br J Cancer. 2008 Aug 5;99(3):442-7. link to original article link to PMC article contains dosing details in abstract PubMed
BACO
BACO: Bleomycin, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine)
Regimen
Study | Evidence |
---|---|
Einhorn et al. 1976 | Non-randomized |
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 PubMed
Carboplatin & Etoposide (CE) & Pembrolizumab
CE & Pembrolizumab: Carboplatin, Etoposide, Pembrolizumab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rudin et al. 2020 (KEYNOTE-604) | 2017-2018 | Phase 3 (E-esc) | 1a. CE 1b. EP |
Seems to have superior OS1 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 contains dosing details in manuscript PubMed NCT03066778
CAV
CAV: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine
CAO: Cyclophosphamide, Adriamycin (Doxorubicin), Oncovin (Vincristine)
Regimen variant #1, 1000/40/1, capped by BSA
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Bunn et al. 1986 | NR 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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Ettinger et al. 1990 | 1982-1985 | Phase 3 (C) | CAV/HEM | Inferior OS | |
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
Regimen variant #3, 1000/50/2, flat-dose vincristine
Study | Years 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 portion 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 contains dosing details in abstract 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 contains dosing details in manuscript PubMed
- 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 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 contains dosing details in manuscript PubMed
CAV/PE
CAV/PE: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine alternating with Platinol (Cisplatin) & Etoposide
Protocol
Study | Years 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
Chemotherapy, PE portion
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 contains dosing details in abstract 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 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
Regimen
Study | Years 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.
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 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
CAE: Cyclophosphamide, Adriamycin (Doxorubicin), Etoposide
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bunn et al. 1986 | NR in abstract | Randomized (E-switch-ic) | CAV | Seems to have superior OS |
Postmus et al. 1996 | 1988-1992 | Phase 3 (C) | CDE/VIMP | Did not meet primary endpoint of 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 |
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. 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 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 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. link to original article PubMed NCT00003696
CEV (Cyclophosphamide/Epirubicin)
CEV: Cyclophosphamide, Epirubicin, Vincristine
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sundstrøm et al. 2002 | 1989-1994 | Phase 3 (C) | Cisplatin & Etoposide | Did not meet primary endpoint of OS |
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 contains dosing details in manuscript PubMed
CEV (Cyclophosphamide/Etoposide)
CEV: Cyclophosphamide, Etoposide, Vincristine
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hong et al. 1989 | NR | Randomized (E-esc) | 1. CAV 2. CV |
Superior OS |
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 PubMed
CEV (Carboplatin/Etoposide)
CEV: Carboplatin, Etoposide, Vincristine
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Reck et al. 2003 | 1998-1999 | Phase 3 (C) | TEC | Seems to have inferior OS |
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 PubMed
Cisplatin & Etoposide (EP) & Pembrolizumab
EP & Pembrolizumab: Etoposide, Platinol (Cisplatin), Pembrolizumab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rudin et al. 2020 (KEYNOTE-604) | 2017-2018 | Phase 3 (E-esc) | 1a. CE 1b. EP |
Seems to have superior OS1 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 contains dosing details in manuscript PubMed NCT03066778
Cyclophosphamide & Lomustine
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ettinger & Lagakos 1982 | 1973-1977 | Phase 3 (C) | Cyclophosphamide, Lomustine, Procarbazine | Seems to have inferior ORR |
Chemotherapy
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 PubMed
Cyclophosphamide, Lomustine, Methotrexate
Regimen
Study | Years 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
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 PubMed
Cyclophosphamide, Lomustine, Procarbazine
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ettinger & Lagakos 1982 | 1973-1977 | Phase 3 (E-esc) | Cyclophosphamide & Lomustine | Seems to have superior ORR |
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 PubMed
EVI
EVI: Epirubicin, Vindesine, Ifosfamide
Regimen
Study | Years 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
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 PubMed
ICE
ICE: Ifosfamide, Carboplatin, Etoposide
Regimen
Study | Years 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
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 PubMed
ICE-V
ICE-V: Ifosfamide, Carboplatin, Etoposide, Vincristine
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Thatcher et al. 2005 (MRC LU21) | NR in abstract | Phase 3 (E-esc) | 1. CDE 2. EP |
Superior OS Median OS: 15.6 vs 11.6 mo (HR 0.74, 95% CI 0.60-0.91) |
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 PubMed NCT00002822
PCDE
PCDE: Platinol (Cisplatin), Cyclophosphamide, EpiDoxorubicin (Epirubicin), Etoposide
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pujol et al. 1997 | 1991-1994 | Phase 3 (C) | PCDE; high-dose | Superior OS |
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 |
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 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 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 PubMed
PCE
PCE: Paclitaxel, Carboplatin, Etoposide
TEC: Taxol (Paclitaxel) Etoposide), Carboplatin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Reck et al. 2003 | 1998-1999 | Phase 3 (E-switch-ic) | CEV | Seems to have superior OS |
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 PubMed
VIP
VIP: Vepesid (Etoposide), Ifosfamide, Platinol (Cisplatin)
Regimen
Study | Years 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 contains dosing details in manuscript PubMed
VMV-VAC
VMV-VAC: Vincristine, Methotrexate, VP-16 (Etoposide), VP-16 (Etoposide), Adriamycin (Doxorubicin), Cyclophosphamide
Regimen
Study | Years 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 |
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 PubMed
Relapsed or refractory disease
CAV
CAV: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine
Regimen variant #1, no capping
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Aix et al. 2022 (ATLANTIS) | 2016-2018 | Phase 3 (C) | Doxorubicin & Lurbinectedin | Did not meet primary endpoint of OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
21-day cycles
Regimen variant #2, capped
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Pawel et al. 1999 | NR | Phase 3 (C) | Topotecan | Did not meet primary endpoints of ORR/DOR |
Note: von Pawel et al. 1999 does not clearly state the duration of each cycle, but 21 days is used in other CAV regimens, and there was no information in the paper that contradicted this.
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 (maximum dose of 2000 mg) (route not specified) once on day 1
- Doxorubicin (Adriamycin) 45 mg/m2 (maximum dose of 100 mg) IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
Supportive therapy
- G-CSF use per physician discretion
21-day cycle for up to 6 cycles beyond maximal response Patients with stable disease after 4 cycles could have treatment discontinued at physician discretion.
Regimen variant #3
Study | Years of enrollment | Evidence |
---|---|---|
Ihde et al. 1994 | 1983-1991 | Non-randomized portion of RCT |
Note: Ihde et al. 1994 did not specifically say that the three medications were all given on day 1, but this is assumed to be the case based on other CAV regimens.
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
21-day cycle for 4 cycles
References
- Ihde DC, Mulshine JL, Kramer BS, Steinberg SM, Linnoila RI, Gazdar AF, Edison M, Phelps RM, Lesar M, Phares JC, Grayson J, Minna JD, Johnson BE. Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. J Clin Oncol. 1994 Oct;12(10):2022-34. link to original article contains dosing details in manuscript PubMed
- von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, Stewart DJ, Clark PI, Palmer MC, Depierre A, Carmichael J, Krebs JB, Ross G, Lane SR, Gralla R. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999 Feb;17(2):658-67. link to original article contains dosing details in manuscript PubMed
- ATLANTIS: Aix SP, Ciuleanu TE, Navarro A, Cousin S, Bonanno L, Smit EF, Chiappori A, Olmedo ME, Horvath I, Grohé C, Farago AF, López-Vilariño JA, Cullell-Young M, Nieto A, Vasco N, Gómez J, Kahatt C, Zeaiter A, Carcereny E, Roubec J, Syrigos K, Lo G, Barneto I, Pope A, Sánchez A, Kattan J, Zarogoulidis K, Waller CF, Bischoff H, Juan-Vidal O, Reinmuth N, Dómine M, Paz-Ares L. Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial. Lancet Respir Med. 2023 Jan;11(1):74-86. Epub 2022 Oct 14. link to original article contains dosing details in abstract PubMed NCT02566993
CDE
CDE: Cyclophosphamide, Doxorubicin, Etoposide
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Postmus et al. 1987 | NR | 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 contains dosing details in manuscript PubMed
Ipilimumab & Nivolumab
Regimen variant #1
Study | Years of enrollment | Evidence |
---|---|---|
Antonia et al. 2016 (CheckMate 032) | 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 | Years of enrollment | Evidence |
---|---|---|
Antonia et al. 2016 (CheckMate 032) | 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 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. link to original article contains dosing details in abstract 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 variant #1, weight-based
Study | Years of enrollment | Evidence |
---|---|---|
Antonia et al. 2016 (CheckMate 032) | 2013-2015 | Phase 1/2 (RT) |
Regimen variant #2, flat dose
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Spigel et al. 2021 (CheckMate 331) | 2015-2017 | Phase 3 (E-switch-ooc) | 1. Amrubicin 2. Topotecan |
Might have superior OS Median OS: 7.5 vs 8.4 mo (HR 0.86, 95% CI 0.72-1.04) |
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. link to original article contains dosing details in abstract 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
- 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 contains dosing details in manuscript PubMed NCT02481830
Pembrolizumab monotherapy
Regimen variant #1, 10 mg/kg q2wk
Study | Years of enrollment | Evidence |
---|---|---|
Ott et al. 2017c (KEYNOTE-028) | 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-158) | Phase 2 |
Note: this arm of KEYNOTE-158 has not been published yet, to our knowledge.
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
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. link to original article contains dosing details in abstract PubMed NCT02054806
- KEYNOTE-158: NCT02628067