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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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.

31 regimens on this page
38 variants on this page


Limited stage, induction

CAV

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CAV: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine

Regimen

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

Chemotherapy

21-day cycle for 6 cycles

References

  1. Johnson DH, Bass D, Einhorn LH, Crawford J, Perez CA, Bartolucci A, Omura GA, Greco FA. 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

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 Evidence Comparator Efficacy
Arriagada et al. 1993 Phase III (E) Lower-dose CC/DE Seems to have superior OS

Chemoradiotherapy

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

CEV & RT

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CEV & RT: Cyclophosphamide, Epirubicin, Vincristine, Radiation Therapy

Regimen

Study Evidence Comparator Efficacy
Perry et al. 1987 (CALGB 8083) Phase III (E) 1. CEV Superior OS
2. CEV, then RT Not reported
Sundstrøm et al. 2002 Phase III (C) Cisplatin, Etoposide, RT Inferior OS

Chemoradiotherapy

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

Extensive stage, induction

ACE

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ACE: Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide
AVE: Adriamycin (Doxorubicin), Vepesid (Etoposide), Endoxan (Cyclophosphamide)

Regimen

Study Evidence Comparator Efficacy
Klastersky et al. 1985 Phase II ORR: 66%
Sculier et al. 1993 Phase III (C) Multi-drug regimen Seems not superior
Baka et al. 2008 Phase III (C) EP Seems not superior

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

CAV

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CAV: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine

Variant #1, 1000/40/1, capped by BSA

Study Evidence Comparator Efficacy Toxicity
Johnson et al. 1987 Phase III (C) HDCAV Seems not superior Less toxic

Chemotherapy

21-day cycle for 6 cycles

Variant #2, 1000/50/1.4, uncapped vincristine

Study Evidence Comparator Efficacy Toxicity
Girling 1996 Phase III (C) Oral Etoposide Seems to have superior OS
Ettinger et al. 2002 (ECOG E1588) Phase III (C) 1. Ifosfamide Seems not superior More toxic
2. Teniposide Seems not superior More toxic

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

Variant #3, 1000/50/2, flat-dose vincristine

Study Evidence Comparator Efficacy Toxicity
Evans et al. 1987 Phase III (C) CAV/PE Seems to have inferior OS Similar toxicity
Maksymiuk et al. 1994 Non-randomized portion of RCT

Chemotherapy

21-day cycle 6 cycles

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. Johnson DH, Einhorn LH, Birch R, Vollmer R, Perez C, Krauss S, Omura G, Greco FA. 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
  3. Maksymiuk AW, Jett JR, Earle JD, Su JQ, Diegert FA, Mailliard JA, Kardinal CG, Krook JE, Veeder MH, Wiesenfeld M, Tschetter LK, Levitt R. 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
  4. 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
  5. ECOG E1588: Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; Eastern Cooperative Oncology Group. 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

Regimen

Study Evidence Comparator Efficacy
Evans et al. 1987 Phase III (E) CAV Seems to have superior OS
Furuse et al. 1998 Phase III (C) CODE Seems not superior

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. Furuse K, Fukuoka M, Nishiwaki Y, Kurita Y, Watanabe K, Noda K, Ariyoshi Y, Tamura T, Saijo N; The Japan Clinical Oncology Group. 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

CDE

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CDE: Cyclophosphamide, Doxorubicin, Etoposide

Regimen

Study Evidence Comparator Efficacy
Postmus et al. 1996 Phase III (C) CDE/VIMP Seems not superior
Ardizzoni et al. 2002 (EORTC 08923) Phase III (C) Intensified CDE Seems not superior
de Jong et al. 2007 Phase III (C) CP Seems not superior

Chemotherapy

References

  1. 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
  2. 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; European Organization for Research and Treatment of Cancer-Lung Cancer Group. Standard versus intensified chemotherapy with granulocyte colony-stimulating factor support in small-cell lung cancer: a prospective European Organization 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
  3. 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

CEV

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CEV: Cyclophosphamide, Epirubicin, Vincristine

Regimen

Study Evidence Comparator Efficacy
Sundstrøm et al. 2002 Phase III (C) Cisplatin & Etoposide Seems not superior

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

EVI

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EVI: Epirubicin, Vindesine, Ifosfamide

Regimen

Study Evidence Comparator Efficacy
Sculier et al. 2001 Phase III (C) 1. Accelerated EVI & GM-CSF Seems not superior
2. Accelerated EVI & antibiotics Seems not superior

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 Evidence Comparator Efficacy
Lorigan et al. 2005 Phase III (C) Dose-dense ICE Seems not superior

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 Evidence Comparator Efficacy
Pujol et al. 1997 Phase III (C) High-dose PCDE Superior OS
Pujol et al. 2001 Phase III (E) EP Superior OS
Pujol et al. 2007 (FNCLCC cleo04 IFCT 00-01) Phase III (C) PCDE & Thalidomide Seems not superior

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

TEC

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TEC: Taxol (Paclitaxel) Etoposide), Carboplatin

Regimen

Study Evidence Comparator Efficacy
Reck et al. 2003 Phase III (E) 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 Evidence Comparator Efficacy
Loehrer et al. 1995 Phase III (E) 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. 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

Relapsed or refractory disease

CAV

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CAV: Cyclophosphamide, Adriamycin (Doxorubicin), Vincristine

Variant #1

Study Evidence Comparator Efficacy
von Pawel et al. 1999 Phase III (C) Topotecan Seems not superior

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 cycles, given until progression of disease, unacceptable toxicity, or 6 cycles beyond maximal response

Patients with stable disease after 4 cycles could have treatment discontinued at physician discretion.

Variant #2

Study Evidence
Ihde et al. 1994 Non-randomized portion of RCT

Treatment given after progression on standard-dose EP versus high-dose EP. Ihde et al. 1994 did not specifically say that the three medications were all given on day 1, but this is assumed to be the case based on other CAV regimens.

Chemotherapy

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
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