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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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 NCCN Guidelines. Is there a regimen missing from this list? See the main SCLC page for current regimens.

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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/m^{2</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

Chemotherapy

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

Chemotherapy

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

External beam 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.

Chemotherapy

Radiotherapy

Concurrent radiation therapy

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
Perry et al. 1987 (CALGB 8083)	1981-1984	Phase 3 (E-esc)	2. CEV, then RT	Not reported
Sundstrøm et al. 2002	1989-1994	Phase 3 (C)	Cisplatin, Etoposide, RT	Inferior OS

Chemotherapy

Radiotherapy

Concurrent radiation therapy

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

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

Used as a comparator arm in older studies. The non-randomized results of Klastersky et al. 1985 established this regimen as a standard control.

Chemotherapy

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

Chemotherapy

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
Ettinger et al. 2002 (ECOG E1588)	1988-1990	Phase 3 (C)	2. Teniposide	Did not meet primary endpoint of OS	More toxic
Girling 1996	1992-1995	Phase 3 (C)	Etoposide; oral	Seems to have superior OS

Chemotherapy

Cyclophosphamide (Cytoxan) 1000 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² IV once on day 1

21-day cycle for 4 to 6 cycles

Subsequent treatment

ECOG E1588, CR: CAV x 2 (6 to 8 total), then PCI
ECOG E1588, PR: CAV until progression of disease, then salvage EP

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.

Chemotherapy

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

Chemotherapy

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

Chemotherapy

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

Chemotherapy

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

Chemotherapy

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

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

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
Sculier et al. 2001	1993-2000	Phase 3 (C)	2. Accelerated EVI & antibiotics	Did not meet primary endpoint of OS

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)

Chemotherapy

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

Chemotherapy

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

Chemotherapy

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

Chemotherapy

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

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.

Preceding treatment

EP; standard-dose versus EP; high-dose, with progression

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
1. 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)

Immunotherapy

Nivolumab (Opdivo) 3 mg/kg IV once on day 1

14-day cycles

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)

Immunotherapy

Nivolumab (Opdivo) 240 mg IV over 30 minutes once on day 1

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
1. 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

@@ Line 3: / Line 3: @@
 [[#top|Back to Top]]
 </div>
-{{#lst:Section editor transclusions|peds}}
+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.
-<big>''This page contains studies that were specific to pediatric populations. For the more general Hodgkin lymphoma page, follow [[Hodgkin lymphoma|this link]].</big><br><br>
-''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Hodgkin_lymphoma_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Hodgkin lymphoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it.''<br>
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
-|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
+|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
-<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
+<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
+|}
+{{TOC limit|limit=3}}
+=Limited stage, induction=
+==CAV {{#subobject:10ggc3|Regimen=1}}==
+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}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1993.11.7.1223 Johnson et al. 1993]
+|1982-1985
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#CAV_.26_RT|CAV & RT]]
+| style="background-color:#fee08b" |Might have inferior OS24
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[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
+*[[Vincristine (Oncovin)]] 1 mg/m<sup>2</sup (maximum dose of 2 mg) IV once on day 1
+'''21-day cycle for 6 cycles'''
+</div></div>
+===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]
+==CAV/PE {{#subobject:106cc3|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
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:4bb088|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1987.5.9.1401 Feld et al. 1987]
+|1981-1984
+| style="background-color:#1a9851" |Randomized (E-switch-ic)
+|[[#CAV-PE_99|CAV-PE]]
+| style="background-color:#ffffbf" |Did not meet efficacy endpoints
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy, CAV portion====
+*[[Cyclophosphamide (Cytoxan)]] as follows:
+**Cycles 1, 3, 5: 1000 mg/m<sup>2</sup> IV once on day 1
+*[[Doxorubicin (Adriamycin)]] as follows:
+**Cycles 1, 3, 5: 50 mg/m<sup>2</sup> 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/m<sup>2</sup> IV once on day 1
+*[[Etoposide (Vepesid)]] as follows:
+**Cycles 2, 4, 6: 100 mg/m<sup>2</sup> IV over 40 to 60 minutes once on day 1
+'''21-day cycle for 6 cycles'''
+</div></div>
+===References===
+# Feld R, Evans WK, Coy P, Hodson I, MacDonald AS, Osoba D, Payne D, Shelley W, Pater JL. Canadian multicenter randomized trial comparing sequential and alternating administration of two non-cross-resistant chemotherapy combinations in patients with limited small-cell carcinoma of the lung. J Clin Oncol. 1987 Sep;5(9):1401-9. [https://doi.org/10.1200/JCO.1987.5.9.1401 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/3040923 PubMed]
+==MACC {{#subobject:219cc3|Regimen=1}}==
+MACC: '''<u>M</u>'''ethotrexate, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>C</u>'''CNU (Lomustine)
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:4ee088|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1985.3.7.969 Maurer et al. 1985 (CALGB 7781)]
+|1977-1981
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|[[#CCV.2FAV_88|CCV/AV]]
+| style="background-color:#ffffbf" |Did not meet endpoint of OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Methotrexate (MTX)]]
+*[[Doxorubicin (Adriamycin)]]
+*[[Cyclophosphamide (Cytoxan)]]
+*[[Lomustine (CCNU)]]
+</div></div>
+===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]
+==VMV-VAC {{#subobject:139cc3|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
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:4cc088|Variant=1}}===
+{| class="wikitable" style="width: 40%; text-align:center;"
+!style="width: 25%"|Study
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1200/JCO.1987.5.4.592 Kies et al. 1987]
+| style="background-color:#91cf61" |Non-randomized portion of RCT
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Vincristine (Oncovin)]]
+*[[Methotrexate (MTX)]]
+*[[Etoposide (Vepesid)]]
+*[[Doxorubicin (Adriamycin)]]
+*[[Cyclophosphamide (Cytoxan)]]
+</div></div>
+===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]
+=Limited stage, definitive chemoradiotherapy=
+==CC/DE & RT {{#subobject:189bcc|Regimen=1}}==
+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}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1056/NEJM199312163292504 Arriagada et al. 1993]
+|1988-1991
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[#CC.2FDE_.26_RT|CC/DE & RT]]; lower-dose
+| style="background-color:#91cf60" |Seems to have superior OS
+|-
 |}
-{{TOC limit|limit=4}}
+<div class="toccolours" style="background-color:#b3e2cd">
-=Guidelines=
+====Chemotherapy====
-==[https://www.nccn.org/ NCCN]==
+*[[Cyclophosphamide (Cytoxan)]]
-*[https://www.nccn.org/professionals/physician_gls/pdf/ped_hodgkin.pdf NCCN Guidelines - Hodgkin Lymphoma (Pediatric and AYA)]
+*[[Cisplatin (Platinol)]]
-=Upfront Therapy, High Risk=
+*[[Doxorubicin (Adriamycin)]]
-==ABVE-PC {{#subobject:67406e|Regimen=1}}==
+*[[Etoposide (Vepesid)]]
-ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide
+====Radiotherapy====
+*[[External beam radiotherapy]]
+</div></div>
+===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]
+==CAV & RT {{#subobject:a37yf8|Regimen=1}}==
+CAV & RT: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine, '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:9134b2|Variant=1}}===
+===Regimen {{#subobject:8801k9|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 27: / Line 163: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1056/nejmoa2206660 Castellino et al. 2022 (COG AHOD1331)]
+|[https://doi.org/10.1200/jco.1984.2.11.1200 Perez et al. 1984]
-|2015-2019
+|1978-1982
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Randomized (E-esc)
-|[[#Bv-AVEPC|Bv-AVEPC]]
+|[[#CAV|CAV]]
-| style="background-color:#d73027" |Inferior EFS
+| style="background-color:#d9ef8b" |Might have superior DFS<sup>1</sup>
+|-
+|[https://doi.org/10.1200/JCO.1990.8.1.33 Jett et al. 1990]
+|1979-1986
+| style="background-color:#1a9851" |Randomized (C)
+|[[#CAVE_.26_RT_99|CAVE & RT]]
+| style="background-color:#ffffbf" |Did not meet endpoint of OS
+|-
+|[https://doi.org/10.1200/JCO.1993.11.7.1223 Johnson et al. 1993]
+|1982-1985
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[#CAV|CAV]]
+| style="background-color:#d9ef8b" |Might have superior OS24<br>OS24: 33% vs 23.5%
 |-
 |}
+''<sup>1</sup>It is not clear from the manuscript what the primary endpont of the study was.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push or intermittent infusion once per day on days 1 & 2
+*[[Cyclophosphamide (Cytoxan)]]
-**Concentration not to exceed 2 mg/mL
+*[[Doxorubicin (Adriamycin)]]
-**IV push over 1 to 5 minutes or by intermittent infusion over 1 to 15 minutes; may prolong to 60 minutes if institutional policies mandate
+*[[Vincristine (Oncovin)]]
-*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SC once on day 1, then 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SC once on day 8
+====Radiotherapy====
-*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1 & 8
+*Concurrent [[External_beam_radiotherapy|radiation therapy]]
-*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 3
-**Rate should not exceed 300 mg/m<sup>2</sup>
-*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 & 2
-====Glucocorticoid therapy====
-*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup> PO twice per day on days 1 to 7
-====Supportive therapy====
-*[[Filgrastim (Neupogen)]] 5 mcg/kg SC (preferred) or IV once per day beginning on day 4, 5, 6, 7, 8, or 9, per institutional policy and continuing until ANC greater than 1000/uL
-**Alternative: [[Pegfilgrastim (Neulasta)]] 100 mcg/kg (Maximum dose of 6 mg) SC once on day 4, 5, or 6
-'''21-day cycle for 2 cycles, then response evaluation, then 21-day cycle for 3 cycles'''
 </div></div>
 ===References===
-# '''COG AHOD1331:''' Castellino SM, Pei Q, Parsons SK, Hodgson D, McCarten K, Horton T, Cho S, Wu Y, Punnett A, Dave H, Henderson TO, Hoppe BS, Charpentier AM, Keller FG, Kelly KM. Brentuximab Vedotin with Chemotherapy in Pediatric High-Risk Hodgkin's Lymphoma. N Engl J Med. 2022 Nov 3;387(18):1649-1660. [https://doi.org/10.1056/nejmoa2206660 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36322844/ PubMed] NCT02166463
+# 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]
-==Bv-AVEPC {{#subobject:67y7uj|Regimen=1}}==
+# 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]
-Bv-AVEPC: '''<u>B</u>'''rentuximab '''<u>v</u>'''edotin, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide
+# 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]
+==CEV & RT {{#subobject:a3e998|Regimen=1}}==
+CEV & RT: '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin, '''<u>V</u>'''incristine, '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:1nc4b2|Variant=1}}===
+===Regimen {{#subobject:88c1d9|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 64: / Line 206: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1056/nejmoa2206660 Castellino et al. 2022 (COG AHOD1331)]
+|rowspan=2|[https://doi.org/10.1056/NEJM198704093161504 Perry et al. 1987 (CALGB 8083)]
-|2015-2019
+|rowspan=2|1981-1984
-| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
+|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#ABVE-PC|ABVE-PC]]
+|1. [[#CEV_.28Cyclophosphamide.2FEpirubicin.29|CEV]]
-| style="background-color:#1a9850" |Superior EFS<br>EFS36: 92.1% vs 82.5%<br>(HR 0.41, 95% CI 0.25-0.67)
+| style="background-color:#1a9850" |Superior OS
+|-
+|2. [[#CEV_.28Cyclophosphamide.2FEpirubicin.29|CEV]], then [[#Radiation_therapy_88|RT]]
+| style="background-color:#d3d3d3" |Not reported
+|-
+|[https://doi.org/10.1200/jco.2002.12.111 Sundstrøm et al. 2002]
+|1989-1994
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[Small_cell_lung_cancer#Cisplatin.2C_Etoposide.2C_RT|Cisplatin, Etoposide, RT]]
+| style="background-color:#d73027" |Inferior OS
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Antibody-drug conjugate therapy====
-*[[Brentuximab vedotin (Adcetris)]] 1.8 mg/kg (maximum dose of 180 mg) IV over 30 minutes once on day 1, '''given prior to chemotherapy'''
-**Do NOT use In Line Filters
 ====Chemotherapy====
-*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push or intermittent infusion once per day on days 1 & 2
+*[[Cyclophosphamide (Cytoxan)]]
-**Concentration not to exceed 2 mg/mL
+*[[Epirubicin (Ellence)]]
-**IV push over 1 to 5 minutes or by intermittent infusion over 1 to 15 minutes; may prolong to 60 minutes if institutional policies mandate
+*[[Vincristine (Oncovin)]]
-*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once on day 8
+====Radiotherapy====
-*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 3
+*Concurrent [[External_beam_radiotherapy|radiation therapy]]
-**Rate should not exceed 300 mg/m<sup>2</sup>
+</div>
-*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 & 2
+<div class="toccolours" style="background-color:#cbd5e7">
-====Glucocorticoid therapy====
+====Subsequent treatment====
-*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup> PO twice per day on days 1 to 7
+*Patients with CR: [[Small_cell_lung_cancer#Whole_brain_irradiation|Prophylactic cranial irradiation]]
-====Supportive therapy====
-*[[Filgrastim (Neupogen)]] 5 mcg/kg SC (preferred) or IV once per day beginning on day 4, 5, 6, 7, 8, or 9, per institutional policy and continuing until ANC greater than 1000/uL
-**Alternative: [[Pegfilgrastim (Neulasta)]] 100 mcg/kg (Maximum dose of 6 mg) SC once on day 4, 5, or 6
-'''21-day cycle for 2 cycles, then response evaluation, then 21-day cycle for 3 cycles'''
 </div></div>
 ===References===
-# '''COG AHOD1331:''' Castellino SM, Pei Q, Parsons SK, Hodgson D, McCarten K, Horton T, Cho S, Wu Y, Punnett A, Dave H, Henderson TO, Hoppe BS, Charpentier AM, Keller FG, Kelly KM. Brentuximab Vedotin with Chemotherapy in Pediatric High-Risk Hodgkin's Lymphoma. N Engl J Med. 2022 Nov 3;387(18):1649-1660. [https://doi.org/10.1056/nejmoa2206660 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36322844/ PubMed] NCT02166463
+# '''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]
-=Upfront Therapy, Intermediate Risk=
+# 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]
-==ABVE-PC {{#subobject:918uu2|Regimen=1}}==
+==Methotrexate, RT, Cyclophosphamide {{#subobject:a4e998|Regimen=1}}==
-ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:941bb2|Variant=1}}===
+===Protocol {{#subobject:78c1d9|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
@@ Line 102: / Line 245: @@
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]
+|[https://doi.org/10.1016/s0140-6736(82)92099-2 Thatcher et al. 1982]
-|2002-2009
+|1978-1981
-| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy, part 1====
+*[[Methotrexate (MTX)]]
+====Radiotherapy====
+*[[External_beam_radiotherapy|Radiation therapy]]
+====Chemotherapy, part 2====
+*[[Cyclophosphamide (Cytoxan)]]
+</div></div>
+===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]
+=Extensive stage, induction=
+==ACE {{#subobject:9fbf31|Regimen=1}}==
+ACE: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide
+<br>AVE: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''epesid (Etoposide), '''<u>E</u>'''ndoxan (Cyclophosphamide)
+<br>CAE: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>E</u>'''toposide
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:949381|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1002/1097-0142%2819850701%2956%3A1%3C71%3A%3AAID-CNCR2820560112%3E3.0.CO%3B2-9 Klastersky et al. 1985]
+|NR
+| style="background-color:#91cf61" |Phase 2
+| style="background-color:#d3d3d3" |
+| ORR: 66%
+|-
+|[https://doi.org/10.1200/JCO.1993.11.10.1858 Sculier et al. 1993]
+|1987-NR
+| style="background-color:#1a9851" |Phase 3 (C)
+|Multi-drug regimen
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527803/ Baka et al. 2008]
+|1999-2005
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[Small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29_2|EP]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS12
+|-
+|}
+''Used as a comparator arm in older studies. The non-randomized results of Klastersky et al. 1985 established this regimen as a standard control.''
+====Chemotherapy====
+*[[Doxorubicin (Adriamycin)]]
+*[[Cyclophosphamide (Cytoxan)]]
+*[[Etoposide (Vepesid)]]
+</div></div>
+===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]
+# 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]
+==BACO {{#subobject:8b52ad|Regimen=1}}==
+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}}===
+{| class="wikitable" style="width: 40%; text-align:center;"
+!style="width: 25%"|Study
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1001/jama.1976.03260380019019 Einhorn et al. 1976]
+| style="background-color:#91cf61" |Non-randomized
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Bleomycin (Blenoxane)]]
+*[[Doxorubicin (Adriamycin)]]
+*[[Cyclophosphamide (Cytoxan)]]
+*[[Vincristine (Oncovin)]]
+</div></div>
+===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]
+==Carboplatin & Etoposide (CE) & Pembrolizumab {{#subobject:o9ga26|Regimen=1}}==
+CE & Pembrolizumab: '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide, Pembrolizumab
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:3cn73m|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ Rudin et al. 2020 (KEYNOTE-604)]
+|2017-2018
+|style="background-color:#1a9851" |Phase 3 (E-esc)
+|1a. [[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]
+| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>OS24: 22.5% vs 11.2%<br>(HR 0.80, 95% CI 0.64-0.98)
 |-
 |}
+''<sup>1</sup>This result did not meet the pre-specified threshold for statistical significance, and was the basis for withdrawal of the FDA indication.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2
+*[[Carboplatin (Paraplatin)]] as follows:
-*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SC once on day 1, then 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SC once on day 8
+**Cycles 1 to 4: AUC 5 IV once on day 1
-*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8
+*[[Etoposide (Vepesid)]] as follows:
-*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 2, 3
+**Cycles 1 to 4: 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
-*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+====Immunotherapy====
-====Glucocorticoid therapy====
+*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
-*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided twice per day or three times per day on days 1 to 7
+'''21-day cycle for up to 35 cycles (2 years)'''
-'''21-day cycle for 2 cycles'''
+</div></div>
+===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
+==CAV {{#subobject:cbb2ff|Regimen=1}}==
+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)
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 1000/40/1, capped by BSA {{#subobject:51b1f9|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 17%"|Study
+!style="width: 15%"|Years of enrollment
+!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 17%"|Comparator
+!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+|-
+|[https://pubmed.ncbi.nlm.nih.gov/3020700 Bunn et al. 1986]
+|NR in abstract
+| style="background-color:#1a9851" |Randomized (C)
+|[[#CDE|CDE]]
+| style="background-color:#fc8d59" |Seems to have inferior OS
+|
+|-
+|[https://doi.org/10.1200/JCO.1987.5.11.1731 Johnson et al. 1987]
+|1982-1984
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#CAV_2|CAV]]; high-dose
+| style="background-color:#ffffbf" |Did not meet endpoint of OS
+| style="background-color:#1a9850" |Less toxic
+|-
+|}
+''Note: the original manuscript with dosing for Bunn et al. 1986 is not available for review.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[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
+*[[Vincristine (Oncovin)]] 1 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+'''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}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 17%"|Study
+!style="width: 15%"|Years of enrollment
+!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 17%"|Comparator
+!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+|-
+|[https://doi.org/10.1200/JCO.1990.8.2.230 Ettinger et al. 1990]
+|1982-1985
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#CAV.2FHEM_88|CAV/HEM]]
+| style="background-color:#d73027" |Inferior OS
+|
+|-
+| rowspan="2" |[https://doi.org/10.1016/s0169-5002(02)00074-0 Ettinger et al. 2002 (ECOG E1588)]
+|rowspan=2|1988-1990
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
+|1. [[Small_cell_lung_cancer#Ifosfamide_monotherapy|Ifosfamide]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#d73027" |More toxic
+|-
+|2. [[Small_cell_lung_cancer#Teniposide_monotherapy|Teniposide]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#d73027" |More toxic
+|-
+|[https://doi.org/10.1016/S0140-6736(96)02005-3 Girling 1996]
+|1992-1995
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Etoposide_monotherapy|Etoposide]]; oral
+| style="background-color:#91cf60" |Seems to have superior OS
+|
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1
+*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycle for 4 to 6 cycles'''
 </div>
 <div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
-*COG AHOD0031, rapid early responders with CR: [[#ABVE-PC|ABVE-PC]] x 2, then [[#Radiation_therapy|IFRT]] versus [[#Observation_88|no further treatment]]
+*ECOG E1588, CR: [[#CAV_2|CAV]] x 2 (6 to 8 total), then [[#Whole_brain_irradiation_2|PCI]]
-*COG AHOD0031, rapid early responders with less than CR: [[#ABVE-PC|ABVE-PC]] x 2, then [[#Radiation_therapy|IFRT]]
+*ECOG E1588, PR: [[#CAV_2|CAV]] until progression of disease, then salvage [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]
-*COG AHOD0031, slow early responders: [[#ABVE-PC|ABVE-PC]] x 2, then [[#Radiation_therapy|IFRT]] versus [[#DECA|DECA]] x 2, then [[#ABVE-PC|ABVE-PC]] x 2, then [[#Radiation_therapy|IFRT]]
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #3, 1000/50/2, flat-dose vincristine {{#subobject:3dc31b|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 17%"|Study
+!style="width: 15%"|Years of enrollment
+!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 17%"|Comparator
+!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+|-
+|[https://jamanetwork.com/journals/jama/article-abstract/352016 Holoye et al. 1977]
+|1973-1974
+| style="background-color:#91cf61" |Non-randomized
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.7326/0003-4819-107-4-451 Evans et al. 1987]
+|1982-1985
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#CAV.2FPE|CAV/PE]]
+| style="background-color:#fc8d59" |Seems to have inferior OS
+| style="background-color:#ffffbf" |Similar toxicity
+|-
+|[https://doi.org/10.1200/JCO.1994.12.1.70 Maksymiuk et al. 1994]
+|1987-1990
+| style="background-color:#91cf61" |Non-randomized portion of RCT
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1
+*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
+'''21-day cycle for 6 cycles'''
+</div></div>
+===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]
+# Bunn PA Jr, Greco FA, Einhorn L. Cyclophosphamide, doxorubicin, and etoposide as first-line therapy in the treatment of small-cell lung cancer. Semin Oncol. 1986 Sep;13(3 Suppl 3):45-53. [https://pubmed.ncbi.nlm.nih.gov/3020700 PubMed]
+# Evans WK, Feld R, Murray N, Willan A, Coy P, Osoba D, Shepherd FA, Clark DA, Levitt M, MacDonald A, Wilson K, Shelley W, Pater J. Superiority of alternating non-cross-resistant chemotherapy in extensive small cell lung cancer: a multicenter, randomized clinical trial by the National Cancer Institute of Canada. Ann Intern Med. 1987 Oct;107(4):451-8. Erratum in: Ann Intern Med 1988 Mar;108(3):496. [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]
+# Johnson DH, Einhorn LH, Birch R, Vollmer R, Perez C, Krauss S, Omura G, Greco FA; Southeastern Cancer Study Group. A randomized comparison of high-dose versus conventional-dose cyclophosphamide, doxorubicin, and vincristine for extensive-stage small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol. 1987 Nov;5(11):1731-8. [https://doi.org/10.1200/JCO.1987.5.11.1731 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2824707 PubMed]
+# Ettinger DS, Finkelstein DM, Abeloff MD, Ruckdeschel JC, Aisner SC, Eggleston JC; [[Study_Groups#ECOG|ECOG]]. A randomized comparison of standard chemotherapy versus alternating chemotherapy and maintenance versus no maintenance therapy for extensive-stage small-cell lung cancer: a phase III study of the Eastern Cooperative Oncology Group. J Clin Oncol. 1990 Feb;8(2):230-40. [https://doi.org/10.1200/JCO.1990.8.2.230 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2153765 PubMed]
+# Maksymiuk AW, Jett JR, Earle JD, Su JQ, Diegert FA, Mailliard JA, Kardinal CG, Krook JE, Veeder MH, Wiesenfeld M, Tschetter LK, Levitt R; North Central Cancer Treatment Group. Sequencing and schedule effects of cisplatin plus etoposide in small-cell lung cancer: results of a North Central Cancer Treatment Group randomized clinical trial. J Clin Oncol. 1994 Jan;12(1):70-6. [https://doi.org/10.1200/JCO.1994.12.1.70 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8270988 PubMed]
+# Girling DJ; Medical Research Council Lung Cancer Working Party. Comparison of oral etoposide and standard intravenous multidrug chemotherapy for small-cell lung cancer: a stopped multicentre randomised trial. Lancet. 1996 Aug 31;348(9027):563-6. [https://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]
+==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
+<div class="toccolours" style="background-color:#eeeeee">
+===Protocol {{#subobject:2a8dee|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1990.8.1.39 Goodman et al. 1990 (SWOG S8232)]
+|1982-1984
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|[[#CAVE|CAVE]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.7326/0003-4819-107-4-451 Evans et al. 1987]
+|1982-1985
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|[[#CAV_2|CAV]]
+| style="background-color:#91cf60" |Seems to have superior OS
+|-
+|[https://doi.org/10.1200/JCO.1992.10.2.282 Roth et al. 1992]
+|1985-1989
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|1. [[#CAV_2|CAV]]<br>2. [[Small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29_2|EP]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS50%
+|-
+|[https://doi.org/10.1200/JCO.1998.16.6.2126 Furuse et al. 1998 (JCOG9106)]
+|1991-1995
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[Stub#CODE|CODE]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS50%
+|-
+|[https://doi.org/10.1200/JCO.1999.17.8.2300 Murray et al. 1999]
+|1992-1996
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[Stub#CODE|CODE]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy, CAV portion====
+*[[Cyclophosphamide (Cytoxan)]]
+*[[Doxorubicin (Adriamycin)]]
+*[[Vincristine (Oncovin)]]
+====Chemotherapy, PE portion====
+*[[Cisplatin (Platinol)]]
+*[[Etoposide (Vepesid)]]
+</div></div>
+===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]
+# '''SWOG S8232:''' Goodman GE, Crowley JJ, Blasko JC, Livingston RB, Beck TM, Demattia MD, Bukowski RM. Treatment of limited small-cell lung cancer with etoposide and cisplatin alternating with vincristine, doxorubicin, and cyclophosphamide versus concurrent etoposide, vincristine, doxorubicin, and cyclophosphamide and chest radiotherapy: a Southwest Oncology Group Study. J Clin Oncol. 1990 Jan;8(1):39-47. [https://doi.org/10.1200/JCO.1990.8.1.39 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2153194 PubMed]
+# Roth BJ, Johnson DH, Einhorn LH, Schacter LP, Cherng NC, Cohen HJ, Crawford J, Randolph JA, Goodlow JL, Broun GO, Omura GA, Greco FA; Southeastern Cancer Study Group. Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol. 1992 Feb;10(2):282-91. [https://doi.org/10.1200/JCO.1992.10.2.282 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1310103 PubMed]
+# '''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]
+==CAVE {{#subobject:55aede|Regimen=1}}==
+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
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:2a8dee|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1990.8.1.39 Goodman et al. 1990 (SWOG S8232)]
+|1982-1984
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#CAV.2FPE|CAV/PE]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.1002/%28SICI)1097-0142%2819971215%2980%3A12%3C2222%3A%3AAID-CNCR2%3E3.0.CO%3B2-W Tummarello et al. 1997]
+|1990-1995
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#CAV-T_99|CAV-T]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS50%
+|-
+|}
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cyclophosphamide (Cytoxan)]]
+*[[Doxorubicin (Adriamycin)]]
+*[[Vincristine (Oncovin)]]
+*[[Etoposide (Vepesid)]]
+</div></div>
+===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]
+# 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: '''<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
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:be62e9|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://pubmed.ncbi.nlm.nih.gov/3020700 Bunn et al. 1986]
+|NR in abstract
+| style="background-color:#1a9851" |Randomized (E-switch-ic)
+|[[#CAV_2|CAV]]
+| style="background-color:#91cf60" |Seems to have superior OS
+|-
+|[https://doi.org/10.1016/0959-8049(96)00145-1 Postmus et al. 1996]
+|1988-1992
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#CDE.2FVIMP_99|CDE/VIMP]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.1200/JCO.2002.02.069 Ardizzoni et al. 2002 (EORTC 08923)]
+|1994-1999
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#CDE|CDE]]; intensified
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.1016/j.ejca.2007.07.029 de Jong et al. 2007 (CKVO-9802)]
+|1999-2005
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_99|CP]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cyclophosphamide (Cytoxan)]]
+*[[Doxorubicin (Adriamycin)]]
+*[[Etoposide (Vepesid)]]
+</div></div>
+===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]
+# Postmus PE, Scagliotti G, Groen HJ, Gozzelino F, Burghouts JT, Curran D, Sahmoud T, Kirkpatrick A, Giaccone G, Splinter TA. Standard versus alternating non-cross-resistant chemotherapy in extensive small cell lung cancer: an EORTC phase III trial. Eur J Cancer. 1996 Aug;32A(9):1498-503. [https://doi.org/10.1016/0959-8049(96)00145-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8911108 PubMed]
+# '''EORTC 08923:''' Ardizzoni A, Tjan-Heijnen VC, Postmus PE, Buchholz E, Biesma B, Karnicka-Mlodkowska H, Dziadziuszko R, Burghouts J, Van Meerbeeck JP, Gans S, Legrand C, Debruyne C, Giaccone G, Manegold C; [[Study_Groups#EORTC|EORTC]]-Lung Cancer Group. Standard versus intensified chemotherapy with granulocyte colony-stimulating factor support in small-cell lung cancer: a prospective European Organisation for Research and Treatment of Cancer-Lung Cancer Group Phase III Trial-08923. J Clin Oncol. 2002 Oct 1;20(19):3947-55. [https://doi.org/10.1200/JCO.2002.02.069 link to original article] [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
+==CEV (Cyclophosphamide/Epirubicin) {{#subobject:ec643a|Regimen=1}}==
+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}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/jco.2002.12.111 Sundstrøm et al. 2002]
+|1989-1994
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[Small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29_2|Cisplatin & Etoposide]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cyclophosphamide (Cytoxan)]]
+*[[Epirubicin (Ellence)]]
+*[[Vincristine (Oncovin)]]
+</div></div>
+===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]
+==CEV (Cyclophosphamide/Etoposide) {{#subobject:eu7r3a|Regimen=1}}==
+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}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1989.7.4.450 Hong et al. 1989]
+|NR
+| style="background-color:#1a9851" |Randomized (E-esc)
+|1. [[#CAV_2|CAV]]<br>2. [[#Cyclophosphamide_.26_Vincristine_.28CV.29_88|CV]]
+| style="background-color:#1a9850" |Superior OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cyclophosphamide (Cytoxan)]]
+*[[Etoposide (Vepesid)]]
+*[[Vincristine (Oncovin)]]
+</div></div>
+===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]
+==CEV (Carboplatin/Etoposide) {{#subobject:ec321a|Regimen=1}}==
+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}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://academic.oup.com/jnci/article/95/15/1118/2520358 Reck et al. 2003]
+|1998-1999
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#PCE|TEC]]
+| style="background-color:#fc8d59" |Seems to have inferior OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]]
+*[[Etoposide (Vepesid)]]
+*[[Vincristine (Oncovin)]]
+</div></div>
+===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]
+==Cisplatin & Etoposide (EP) & Pembrolizumab {{#subobject:eeja26|Regimen=1}}==
+EP & Pembrolizumab: '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin), Pembrolizumab
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:3ci91m|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ Rudin et al. 2020 (KEYNOTE-604)]
+|2017-2018
+|style="background-color:#1a9851" |Phase 3 (E-esc)
+|1a. [[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]<br>1b. [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]
+| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>OS24: 22.5% vs 11.2%<br>(HR 0.80, 95% CI 0.64-0.98)
+|-
+|}
+''<sup>1</sup>This result did not meet the pre-specified threshold for statistical significance, and was the basis for withdrawal of the FDA indication.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] as follows:
+**Cycles 1 to 4: 75 mg/m<sup>2</sup> IV once on day 1
+*[[Etoposide (Vepesid)]] as follows:
+**Cycles 1 to 4: 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+====Immunotherapy====
+*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
+'''21-day cycle for up to 35 cycles (2 years)'''
+</div></div>
+===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
+==Cyclophosphamide & Lomustine {{#subobject:ab365b|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:th1b8b|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1002/1097-0142(19820415)49:8%3C1544::aid-cncr2820490806%3E3.0.co;2-j Ettinger & Lagakos 1982]
+|1973-1977
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Cyclophosphamide.2C_Lomustine.2C_Procarbazine|Cyclophosphamide, Lomustine, Procarbazine]]
+| style="background-color:#fc8d59" |Seems to have inferior ORR
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cyclophosphamide (Cytoxan)]]
+*[[Lomustine (CCNU)]]
+</div></div>
+===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]
+==Cyclophosphamide, Lomustine, Methotrexate {{#subobject:ab343a|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:e4338b|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://jamanetwork.com/journals/jama/fullarticle/364557 Cohen et al. 1979]
+|1975-1977
+| style="background-color:#1a9851" |Phase 3 (C)
+|Chemotherapy & Thymosin fraction V
+| style="background-color:#fc8d59" |Seems to have inferior OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cyclophosphamide (Cytoxan)]]
+*[[Lomustine (CCNU)]]
+*[[Methotrexate (MTX)]]
+</div></div>
+===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]
+==Cyclophosphamide, Lomustine, Procarbazine {{#subobject:abug71|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:thg1tb|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1002/1097-0142(19820415)49:8%3C1544::aid-cncr2820490806%3E3.0.co;2-j Ettinger & Lagakos 1982]
+|1973-1977
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[#Cyclophosphamide_.26_Lomustine|Cyclophosphamide & Lomustine]]
+| style="background-color:#91cf60" |Seems to have superior ORR
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cyclophosphamide (Cytoxan)]]
+*[[Lomustine (CCNU)]]
+*[[Procarbazine (Matulane)]]
+</div></div>
+===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]
+==EVI {{#subobject:21fa55|Regimen=1}}==
+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}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363948/ Sculier et al. 2001]
+|rowspan=2|1993-2000
+|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#EVI_.26_GM-CSF_99|EVI & GM-CSF]]; accelerated
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|2. Accelerated EVI & antibiotics
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|}
+''Not commonly used but was a comparator arm for at least one RCT; here for reference purposes only.''
+====Chemotherapy====
+*[[Epirubicin (Ellence)]]
+*[[Vindesine (Eldisine)]]
+*[[Ifosfamide (Ifex)]]
+</div></div>
+===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]
+==ICE {{#subobject:f535c2|Regimen=1}}==
+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}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://academic.oup.com/jnci/article/97/9/666/2544232 Lorigan et al. 2005]
+|1994-2001
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Dose-dense_ICE.2C_then_auto_HSCT_99|Dose-dense ICE, then auto HSCT]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Ifosfamide (Ifex)]]
+*[[Carboplatin (Paraplatin)]]
+*[[Etoposide (Vepesid)]]
+</div></div>
+===References===
+# Lorigan P, Woll PJ, O'Brien ME, Ashcroft LF, Sampson MR, Thatcher N. Randomized phase III trial of dose-dense chemotherapy supported by whole-blood hematopoietic progenitors in better-prognosis small-cell lung cancer. J Natl Cancer Inst. 2005 May 4;97(9):666-74. Erratum in: J Natl Cancer Inst. 2005 Jun 15;97(12):941. [https://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: '''<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}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/jco.2004.00.9969 Thatcher et al. 2005 (MRC LU21)]
+|NR in abstract
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|1. [[#CDE|CDE]]<br>2. [[Small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]
+| style="background-color:#1a9850" |Superior OS<br>Median OS: 15.6 vs 11.6 mo<br>(HR 0.74, 95% CI 0.60-0.91)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Ifosfamide (Ifex)]]
+*[[Carboplatin (Paraplatin)]]
+*[[Etoposide (Vepesid)]]
+*[[Vincristine (Oncovin)]]
+</div></div>
+===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
+==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
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:bc58e8|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1997.15.5.2082 Pujol et al. 1997]
+|1991-1994
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#PCDE|PCDE]]; high-dose
+| style="background-color:#1a9850" |Superior OS
+|-
+|[https://academic.oup.com/jnci/article/93/4/300/2906465 Pujol et al. 2001 (FNCLCC 95012)]
+|1996-1999
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[Small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29_2|EP]]
+| style="background-color:#1a9850" |Superior OS
+|-
+|[https://doi.org/10.1200/JCO.2007.11.8109 Pujol et al. 2007 (FNCLCC cleo04 IFCT 00-01)]
+|2000-2004
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#PCDE_.26_Thalidomide_99|PCDE & Thalidomide]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]]
+*[[Cyclophosphamide (Cytoxan)]]
+*[[Epirubicin (Ellence)]]
+*[[Etoposide (Vepesid)]]
 </div></div>
 ===References===
-# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain dosing details''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259
+# 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]
-==DECA {{#subobject:jqqcu2|Regimen=1}}==
+# '''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
-DECA: '''<u>D</u>'''examethasone, '''<u>E</u>'''toposide, '''<u>C</u>'''isplatin, '''<u>A</u>'''ra-C (Cytarabine)
+# '''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: '''<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
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:94172v|Variant=1}}===
+===Regimen {{#subobject:b2c397|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://academic.oup.com/jnci/article/95/15/1118/2520358 Reck et al. 2003]
+|1998-1999
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|[[#CEV_.28Carboplatin.2FEtoposide.29|CEV]]
+| style="background-color:#91cf60" |Seems to have superior OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]]
+*[[Carboplatin (Paraplatin)]]
+*[[Etoposide (Vepesid)]]
+</div></div>
+===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]
+==VIP {{#subobject:8703fa|Regimen=1}}==
+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}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1995.13.10.2594 Loehrer et al. 1995]
+|1989-1993
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[Small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29_2|Cisplatin & Etoposide]]
+| style="background-color:#91cf60" |Seems to have superior OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[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
+*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 4
+'''21-day cycle for 4 cycles'''
+</div></div>
+===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]
+==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
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:5dd088|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1984.2.6.585 Livingston et al. 1984 (SWOG S7828)]
+|1978-1980
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|1. [[#CAV_2|VAC]]<br>2. [[#VMV_88|VMV]]
+| style="background-color:#ffffbf" |Did not meet endpoint of OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Vincristine (Oncovin)]]
+*[[Methotrexate (MTX)]]
+*[[Etoposide (Vepesid)]]
+*[[Doxorubicin (Adriamycin)]]
+*[[Cyclophosphamide (Cytoxan)]]
+</div></div>
+===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]
+=Relapsed or refractory disease=
+==CAV {{#subobject:d3d3e|Regimen=1}}==
+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}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/s2213-2600(22)00309-5 Aix et al. 2022 (ATLANTIS)]
+|2016-2018
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Doxorubicin_.26_Lurbinectedin|Doxorubicin & Lurbinectedin]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1
+*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1
+*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
+'''21-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, capped {{#subobject:83cdbf|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/jco.1999.17.2.658 von Pawel et al. 1999]
+|NR
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[Small_cell_lung_cancer#Topotecan_monotherapy|Topotecan]]
+| style="background-color:#ffffbf" |Did not meet primary endpoints of ORR/DOR
+|-
+|}
+''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/m<sup>2</sup> (maximum dose of 2000 mg) (route not specified) once on day 1
+*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> (maximum dose of 100 mg) IV once on day 1
+*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
+====Supportive therapy====
+*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] use per physician discretion
+'''21-day cycle for up to 6 cycles beyond maximal response'''
+''Patients with stable disease after 4 cycles could have treatment discontinued at physician discretion.''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #3 {{#subobject:531cce|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
@@ Line 135: / Line 1,075: @@
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]
+|[https://doi.org/10.1200/jco.1994.12.10.2022 Ihde et al. 1994]
-|2002-2009
+|1983-1991
-| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
-''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
+''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====
-*[[#ABVE-PC_2|ABVE-PC]] x 2, with slow early response
+*[[#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">
-====Glucocorticoid therapy====
-*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup> IV over 15 minutes on days 1, 2, '''given prior to etoposide/cytarabine'''
 ====Chemotherapy====
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 2
+*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1
-**Mix [[Etoposide (Vepesid)]] with [[Cytarabine (Ara-C)]] in D5W at an [[Etoposide (Vepesid)]] concentration of ≤ 0.4 mg/mL
+*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1
-*[[Cisplatin (Platinol)]] 90 mg/m<sup>2</sup> IV over 6 hours once on day 1
+*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
-*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours on days 1, 2
+'''21-day cycle for 4 cycles'''
-**Mix [[Etoposide (Vepesid)]] with [[Cytarabine (Ara-C)]] in D5W at an [[Etoposide (Vepesid)]] concentration of ≤ 0.4 mg/mL
-'''21-day cycle for 2 cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#ABVE-PC_2|ABVE-PC]] x 2, then [[#Radiation_therapy|IFRT]]
 </div></div>
 ===References===
-# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain dosing details''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259
+# 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]
-=Upfront Therapy, Low Risk=
+# 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]
-==OEPA (GPOD-HD-2002) {{#subobject:0e614f|Regimen=1}}==
+#'''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
-OEPA: '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)
+==CDE {{#subobject:fd0ec6|Regimen=1}}==
+CDE: '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''oxorubicin, '''<u>E</u>'''toposide
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:25c262|Variant=1}}===
+===Regimen {{#subobject:65860f|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
 !style="width: 33%"|Years of enrollment
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]
+|[https://doi.org/10.1016/0277-5379(87)90128-3 Postmus et al. 1987]
-|2002-2005
+|NR
 | style="background-color:#91cf61" |Phase 2
 |-
 |}
-''This regimen is meant for boys as it is potentially less gonadotoxic. The original protocol used three doses of dacarbazine per cycle but this was increased to four after a mid-protocol amendment. Patients with early-stage disease only received the OEPA portion, see text for details.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV once per day on days 2 to 6
+*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1
-*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 15
+*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
-====Glucocorticoid therapy====
+'''21-day cycle for 5 cycles'''
-*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 15
+</div></div>
-'''28-day cycle for 2 cycles'''
+===References===
-</div>
+# 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]
-<div class="toccolours" style="background-color:#cbd5e7">
+==Ipilimumab & Nivolumab {{#subobject:7bc416|Regimen=1}}==
-====Subsequent treatment====
+<div class="toccolours" style="background-color:#eeeeee">
-*Treatment group 2: [[#COPDAC|COPDAC]] x 2
+===Regimen variant #1 {{#subobject:aa43c1|Variant=1}}===
-*Treatment group 3: [[#COPDAC|COPDAC]] x 4
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Years of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1016/S1470-2045(16)30098-5 Antonia et al. 2016 (CheckMate 032)]
+|2013-2015
+| style="background-color:#91cf61" |Phase 1/2 (RT)
+|-
+|}
+''Note: it is unclear which schedule of ipilimumab & nivolumab is preferred based on the abstract.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====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'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2 {{#subobject:b6a1ee|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Years of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1016/S1470-2045(16)30098-5 Antonia et al. 2016 (CheckMate 032)]
+|2013-2015
+| style="background-color:#91cf61" |Phase 1/2 (RT)
+|-
+|}
+''Note: it is unclear which schedule of ipilimumab & nivolumab is preferred based on the abstract.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====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'''
 </div></div>
 ===References===
-# '''GPOH-HD-2002:''' Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832
+# '''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
-=Consolidation therapy=
+##'''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]
-==Radiation therapy {{#subobject:b169ea|Regimen=1}}==
+==Nivolumab monotherapy {{#subobject:67a13c|Regimen=1}}==
-RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:dfa48c|Variant=1}}===
+===Regimen variant #1, weight-based {{#subobject:5a9324|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Years of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1016/S1470-2045(16)30098-5 Antonia et al. 2016 (CheckMate 032)]
+|2013-2015
+| style="background-color:#91cf61" |Phase 1/2 (RT)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Immunotherapy====
+*[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1
+'''14-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, flat dose {{#subobject:5a8guac|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
 !style="width: 20%"|Years of enrollment
@@ Line 205: / Line 1,192: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.2002.12.007 Nachman et al. 2002 (CCG 5942)]
+|[https://doi.org/10.1016/j.annonc.2021.01.071 Spigel et al. 2021 (CheckMate 331)]
-|1995-1998
+|2015-2017
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
-|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]
+|1. [[Small_cell_lung_cancer#Amrubicin_monotherapy|Amrubicin]]<br>2. [[Small_cell_lung_cancer#Topotecan_monotherapy|Topotecan]]
-| style="background-color:#1a9850" |Superior EFS
+| style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: 7.5 vs 8.4 mo<br>(HR 0.86, 95% CI 0.72-1.04)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Immunotherapy====
+*[[Nivolumab (Opdivo)]] 240 mg IV over 30 minutes once on day 1
+'''14-day cycles'''
+</div></div>
+===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
+##'''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
+==Pembrolizumab monotherapy {{#subobject:bc1cf4|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 10 mg/kg q2wk {{#subobject:96a1cg|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Years of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1200/JCO.2017.72.5069 Ott et al. 2017c (KEYNOTE-028)]
+|2014-2015
+| style="background-color:#91cf61" |Phase 1b (RT)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Immunotherapy====
+*[[Pembrolizumab (Keytruda)]] 10 mg/kg IV once on day 1
+'''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}}===
+{| class="wikitable" style="color:white; background-color:#404040"
+|<small>'''FDA-recommended dose'''</small>
+|-
+|}
+{| class="wikitable" style="width: 40%; text-align:center;"
+! style="width: 50%" |Study
+! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]
+|[https://www.clinicaltrials.gov/ct2/show/NCT02628067 Awaiting publication (KEYNOTE-158)]
-|1997-2001
 | style="background-color:#91cf61" |Phase 2
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]
-|2002-2009
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS48
 |-
 |}
-''This regimen is intended for pediatric patients, younger than 22 years old.''
+''Note: this arm of KEYNOTE-158 has not been published yet, to our knowledge.''
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*CCG 5942: [[#C-MOPP.2FABV|COPP-ABV hybrid]] x 4 or 6 or multi-drug therapy, depending on risk stratification
-*POG P9425: [[#ABVE-PC|ABVE-PC]] x 3 to 5
-*COG AHOD0031 RERs: [[#ABVE-PC|ABVE-PC]] x 4
-*COG AHOD0031 SERs: [[#ABVE-PC|ABVE-PC]] x 4 versus [[#ABVE-PC|ABVE-PC]] x 2, then DECA x 2, then [[#ABVE-PC|ABVE-PC]] x 2
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Radiotherapy====
+====Immunotherapy====
-*[[External beam radiotherapy]] 21 Gy in 12 to 14 fractions of 1.5 to 1.75 Gy per fraction
+*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
+'''21-day cycle for up to 35 cycles (2 years)'''
 </div></div>
 ===References===
-# '''CCG 5942:''' Nachman JB, Sposto R, Herzog P, Gilchrist GS, Wolden SL, Thomson J, Kadin ME, Pattengale P, Davis PC, Hutchinson RJ, White K; Children's Cancer Group. Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. J Clin Oncol. 2002 Sep 15;20(18):3765-71. [https://doi.org/10.1200/JCO.2002.12.007 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12228196 PubMed] NCT00592111
+# '''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
-## '''Update:''' Wolden SL, Chen L, Kelly KM, Herzog P, Gilchrist GS, Thomson J, Sposto R, Kadin ME, Hutchinson RJ, Nachman J. Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with Hodgkin's lymphoma--a report from the Children's Oncology Group. J Clin Oncol. 2012 Sep 10;30(26):3174-80. Epub 2012 May 29. [https://doi.org/10.1200/JCO.2011.41.1819 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434976/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22649136 PubMed]
+# '''KEYNOTE-158:''' NCT02628067
-# '''POG P9425:''' Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578
+[[Category:Small cell lung cancer regimens]]
-# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain dosing details''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259
+[[Category:Historical regimens]]
-[[Category:Hodgkin lymphoma regimens]]
 [[Category:Disease-specific pages]]
-[[Category:Aggressive lymphomas]]
+[[Category:Lung cancers]]
-[[Category:Pediatric hematologic neoplasms]]

Difference between revisions of "Staging page"

Revision as of 14:11, 28 December 2022

Limited stage, induction

CAV

Regimen

Chemotherapy

References

CAV/PE

Regimen

Chemotherapy, CAV portion

Chemotherapy, PE portion

References

MACC

Regimen

Chemotherapy

References

VMV-VAC

Regimen

Chemotherapy

References

Limited stage, definitive chemoradiotherapy

CC/DE & RT

Regimen

Chemotherapy

Radiotherapy

References

CAV & RT

Regimen

Chemotherapy

Radiotherapy

References

CEV & RT

Regimen

Chemotherapy

Radiotherapy

Subsequent treatment

References

Methotrexate, RT, Cyclophosphamide

Protocol

Chemotherapy, part 1

Radiotherapy

Chemotherapy, part 2

References

Extensive stage, induction

ACE

Regimen

Chemotherapy

References

BACO

Regimen

Chemotherapy

References

Carboplatin & Etoposide (CE) & Pembrolizumab

Regimen

Chemotherapy

Immunotherapy

References

CAV

Regimen variant #1, 1000/40/1, capped by BSA

Chemotherapy

Regimen variant #2, 1000/50/1.4, uncapped vincristine

Chemotherapy

Subsequent treatment

Regimen variant #3, 1000/50/2, flat-dose vincristine

Chemotherapy

References

CAV/PE

Protocol

Chemotherapy, CAV portion

Chemotherapy, PE portion

References

CAVE

Regimen

Chemotherapy

References

CDE

Regimen

Chemotherapy

References

CEV (Cyclophosphamide/Epirubicin)