Small cell lung cancer - historical

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the NCCN Guidelines. Is there a regimen missing from this list? See the main SCLC page for current regimens.

23 regimens on this page
25 variants on this page

Contents


Limited stage, induction

CAV

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CAV: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine

Regimen

Study Evidence
Feld et al. 1987 Non-randomized portion of RCT
Johnson et al. 1993 Non-randomized portion of RCT

Chemotherapy

21-day cycle for 6 cycles

References

  1. 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 PubMed
  2. 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 PubMed

MACC

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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 III (E) CCV/AV Did not meet endpoint of OS

Chemotherapy

References

  1. 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

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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

  1. 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

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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 III (E-esc) CC/DE & RT]]; lower-dose Seems to have superior OS

Chemotherapy

Radiotherapy

References

  1. 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

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CAV & RT: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine, Radiation Therapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Jett et al. 1990 1979-1986 Randomized (C) CAVE & RT Did not meet endpoint of OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.

Chemotherapy

Radiotherapy

References

  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. link to original article PubMed

CEV & RT

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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 III (E-esc) 1. CEV Superior OS
2. CEV, then RT Not reported
Sundstrøm et al. 2002 1989-1994 Phase III (C) Cisplatin, Etoposide, RT Inferior OS

Chemotherapy

Radiotherapy

Subsequent treatment

References

  1. 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
  2. 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 verified protocol PubMed

Methotrexate, RT, Cyclophosphamide

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Protocol

Study Evidence
Thatcher et al. 1982 Non-randomized portion of RCT

Chemotherapy, part 1

Radiotherapy

Chemotherapy, part 2

References

  1. 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

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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 II ORR: 66%
Sculier et al. 1993 1987-NR Phase III (C) Multi-drug regimen Did not meet primary endpoint of OS
Baka et al. 2008 1999-2005 Phase III (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

  1. 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
  2. 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
  3. 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 protocol PubMed

BACO

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BACO: Bleomycin, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine)

Regimen

Study Evidence
Einhorn et al. 1976 Non-randomized

Chemotherapy

References

  1. 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

CAV

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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 III (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

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 III (C) CAV/HEM Inferior OS
Ettinger et al. 2002 (ECOG E1588) 1988-1990 Phase III (C) 1. Ifosfamide Did not meet primary endpoint of OS More toxic
2. Teniposide Did not meet primary endpoint of OS More toxic
Girling 1996 1992-1995 Phase III (C) Oral Etoposide Seems to have superior OS

Chemotherapy

21-day cycle for 4 to 6 cycles

Subsequent treatment

  • ECOG E1588, CR: 2 more cycles of CAV, 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 III (C) CAV/PE Seems to have inferior OS Similar toxicity
Maksymiuk et al. 1994 1987-1990 Non-randomized portion of RCT

Chemotherapy

21-day cycle 6 cycles

References

  1. 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
  2. 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
  3. 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 protocol PubMed
  4. 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 verified protocol PubMed
  5. 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
  6. 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
  7. 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
  8. 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 verified protocol PubMed

CAV/PE

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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 III (E-switch-ic) CAVE Did not meet primary endpoint of OS
Evans et al. 1987 1982-1985 Phase III (E-switch-ic) CAV Seems to have superior OS
Roth et al. 1992 1985-1989 Phase III (E-esc) 1. CAV
2. EP
Did not meet primary endpoint of OS50%
Furuse et al. 1998 (JCOG9106) 1991-1995 Phase III (C) CODE Did not meet primary endpoint of OS50%
Murray et al. 1999 1992-1996 Phase III (C) CODE Did not meet primary endpoint of OS

Chemotherapy, CAV portion

Chemotherapy, PE portion

References

  1. 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 protocol PubMed
  2. 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
  3. 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
  4. 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
  5. 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

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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 III (C) CAV/PE Did not meet primary endpoint of OS
Tummarello et al. 1997 1990-1995 Phase III (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 prior to becoming a standard comparator arm.

Chemotherapy

References

  1. 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
  2. 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

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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 III (C) CDE/VIMP Did not meet primary endpoint of OS
Ardizzoni et al. 2002 (EORTC 08923) 1994-1999 Phase III (C) CDE; intensified Did not meet primary endpoint of OS
de Jong et al. 2007 (CKVO-9802) 1999-2005 Phase III (C) CP Did not meet primary endpoint of PFS

Chemotherapy

References

  1. 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
  2. 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
  3. 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
  4. 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)

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CEV: Cyclophosphamide, Epirubicin, Vincristine

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Sundstrøm et al. 2002 1989-1994 Phase III (C) Cisplatin & Etoposide Did not meet primary endpoint of OS

Chemotherapy

References

  1. 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 verified protocol PubMed

CEV (Cyclophosphamide/Etoposide)

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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

  1. 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)

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CEV: Carboplatin, Etoposide, Vincristine

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Reck et al. 2003 1998-1999 Phase III (C) TEC Seems to have inferior OS

Chemotherapy

References

  1. 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

Cyclophosphamide, Lomustine, Methotrexate

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Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Cohen et al. 1979 1975-1977 Phase III (C) Chemotherapy & Thymosin fraction V Seems to have inferior OS

Chemotherapy

References

  1. 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

EVI

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EVI: Epirubicin, Vindesine, Ifosfamide

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Sculier et al. 2001 1993-2000 Phase III (C) 1. Accelerated EVI & GM-CSF Did not meet primary endpoint of OS
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

  1. 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

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ICE: Ifosfamide, Carboplatin, Etoposide

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Lorigan et al. 2005 1994-2001 Phase III (C) Dose-dense ICE, then auto HSCT Did not meet primary endpoint of OS

Chemotherapy

References

  1. 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

PCDE

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PCDE: Platinol (Cisplatin), Cyclophosphamide, EpiDoxorubicin (Epirubicin), Etoposide

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Pujol et al. 1997 1991-1994 Phase III (C) PCDE; high-dose Superior OS
Pujol et al. 2001 1996-1999 Phase III (E-esc) EP Superior OS
Pujol et al. 2007 (FNCLCC cleo04 IFCT 00-01) 2000-2004 Phase III (C) PCDE & Thalidomide Did not meet primary endpoint of OS

Chemotherapy

References

  1. 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
  2. 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
  3. 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

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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 III (E-switch-ic) CEV Seems to have superior OS

Chemotherapy

References

  1. 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

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VIP: Vepesid (Etoposide), Ifosfamide, Platinol (Cisplatin)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Loehrer et al. 1995 1989-1993 Phase III (E-esc) Cisplatin & Etoposide Seems to have superior OS

Chemotherapy

21-day cycle for 4 cycles

References

  1. 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 verified protocol PubMed

VMV-VAC

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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 III (E-esc) 1. VAC
2. VMV
Did not meet endpoint of OS

Chemotherapy

References

  1. 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

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CAV: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine

Regimen variant #1

Study Years of enrollment Evidence Comparator Comparative Efficacy
von Pawel et al. 1999 NR Phase III (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

Supportive medications

  • 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 #2

Study Evidence
Ihde et al. 1994 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

Chemotherapy

21-day cycle for 4 cycles

References

  1. 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 verified protocol PubMed
  2. 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 verified protocol PubMed

CDE

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CDE: Cyclophosphamide, Doxorubicin, Etoposide

Regimen

Study Evidence
Postmus et al. 1987 Phase II

Chemotherapy

References

  1. 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. PubMed