What is the optimal chemotherapy regimen and duration of therapy in extensive stage small cell lung cancer in the first-line setting?

From Cancer Guidelines Wiki

What is the optimal chemotherapy regimen and duration of therapy in extensive stage small cell lung cancer in the first-line setting?

Based on the current evidence including randomised phase II;[1] [2] and phase III trials;[3][4][5][6][7] platinum etopside combination is still considered as the gold standard.[8]

Based on phase III trials[9][10][11][12] and subsequent meta-analyses[13][14] Irinotecan combined with platinum may be as efficacious, with differing toxicity profiles. However, the data is heterogeneous and in some studies in favor of non-Caucasion population.[2]

The utility of triplet combinations have provided no additional benefit based on phase II trials[15][16]

No studies have directly compared four versus six cycles of therapy in the first-line setting.

The use of maintenance or consolidation therapy after initial response to first-line therapy has not been shown to be of added benefit in terms of overall survival whether evaluating single agent cytotoxic agents such as Irinotecan or biologicals such as thalidomide or marimastat. Sunitinib may provide benefit when assessed in phase II trial.[17]

This conclusion is based upon phase II,[18] and randomised phase III trials.[19][20]

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Evidence summary and recommendations

Evidence summary Level References
The platinum etoposide combination is still considered as the standard first-line regimen.

Last reviewed December 2015

II [1], [3], [4], [5], [6]
Irinotecan combined with platinum may be as efficacious as platinum etoposide in specific populations but with differing toxicity profiles.

Last reviewed December 2015

I, II [13], [14], [9], [10], [11], [12]
The utility of triplet combinations have provided no additional benefit.

Last reviewed December 2015

II [15], [16]
The use of maintenance or consolidation therapy after initial response to first-line therapy has not been shown to be of added benefit.

Last reviewed December 2015

II [18], [19], [20]
Evidence-based recommendationQuestion mark transparent.png Grade
The platinum etoposide regimen is recommended as the first-line therapy for patients with extensive stage small cell lung cancer. Irinotecan-platinum may be an alternative in selected patients.

Last reviewed December 2015

B


Practice pointQuestion mark transparent.png

It is advisable to consider the platinum etoposide regimen as first-line therapy in patients with extensive stage small cell lung cancer, treatment should continue for at least four to six cycles. Maintenance therapy provides no aditional benefit.
Last reviewed December 2015

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References

  1. 1.0 1.1 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12234701.
  2. 2.0 2.1 Shi Y, Hu Y, Hu X, Li X, Lin L, Han X. Cisplatin combined with irinotecan or etoposide for untreated extensive-stage small cell lung cancer: A multicenter randomized controlled clinical trial. Thorac Cancer 2015 Nov;6(6):785-91 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26557919.
  3. 3.0 3.1 Eckardt JR, von Pawel J, Papai Z, Tomova A, Tzekova V, Crofts TE, et al. Open-label, multicenter, randomized, phase III study comparing oral topotecan/cisplatin versus etoposide/cisplatin as treatment for chemotherapy-naive patients with extensive-disease small-cell lung cancer. J Clin Oncol 2006 May 1;24(13):2044-51 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16648504.
  4. 4.0 4.1 Schmittel A, Sebastian M, Fischer von Weikersthal L, Martus P, Gauler TC, Kaufmann C, et al. A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol 2011 Aug;22(8):1798-804 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21266516.
  5. 5.0 5.1 Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, et al. 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12488411.
  6. 6.0 6.1 Socinski MA, Smit EF, Lorigan P, Konduri K, Reck M, Szczesna A, et al. Phase III study of pemetrexed plus carboplatin compared with etoposide plus carboplatin in chemotherapy-naive patients with extensive-stage small-cell lung cancer. J Clin Oncol 2009 Oct 1;27(28):4787-92 Abstract available at HTTP://WWW.NCBI.NLM.NIH.GOV/PUBMED/19720897.
  7. Sekine I, Okamoto H, Horai T, Nakagawa K, Ohmatsu H, Yokoyama A, et al. A Randomized Phase III Study of Single-Agent Amrubicin Vs. Carboplatin/Etoposide in Elderly Patients With Extensive-Disease Small-Cell Lung Cancer. Clin Lung Cancer 2013 Nov 14 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24361248.
  8. Jiang L, Yang KH, Guan QL, Mi DH, Wang J. Cisplatin plus etoposide versus other platin-based regimens for patients with extensive small cell lung cancer: a systematic review and meta analysis of randomized controlled trials. Intern Med J 2012 Apr 25 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22530708.
  9. 9.0 9.1 Hanna N, Bunn PA Jr, Langer C, Einhorn L, Guthrie T Jr, Beck T, et al. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol 2006 May 1;24(13):2038-43 Abstract available at HTTP://WWW.NCBI.NLM.NIH.GOV/PUBMED/16648503.
  10. 10.0 10.1 Lara PN Jr, Natale R, Crowley J, Lenz HJ, Redman MW, Carleton JE, et al. Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124. J Clin Oncol 2009 May 20;27(15):2530-5 Abstract available at HTTP://WWW.NCBI.NLM.NIH.GOV/PUBMED/19349543.
  11. 11.0 11.1 Zatloukal P, Cardenal F, Szczesna A, Gorbunova V, Moiseyenko V, Zhang X, et al. A multicenter international randomized phase III study comparing cisplatin in combination with irinotecan or etoposide in previously untreated small-cell lung cancer patients with extensive disease. Ann Oncol 2010 Sep;21(9):1810-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20231298.
  12. 12.0 12.1 Hermes A, Bergman B, Bremnes R, Ek L, Fluge S, Sederholm C, et al. Irinotecan plus carboplatin versus oral etoposide plus carboplatin in extensive small-cell lung cancer: a randomized phase III trial. J Clin Oncol 2008 Sep 10;26(26):4261-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18779613.
  13. 13.0 13.1 Jiang J, Liang X, Zhou X, Huang L, Huang R, Chu Z, et al. A meta-analysis of randomized controlled trials comparing irinotecan/platinum with etoposide/platinum in patients with previously untreated extensive-stage small cell lung cancer. J Thorac Oncol 2010 Jun;5(6):867-73 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20521354.
  14. 14.0 14.1 Lima JP, dos Santos LV, Sasse EC, Lima CS, Sasse AD. Camptothecins compared with etoposide in combination with platinum analog in extensive stage small cell lung cancer: systematic review with meta-analysis. J Thorac Oncol 2010 Dec;5(12):1986-93 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20978445.
  15. 15.0 15.1 Greco FA, Thompson DS, Morrissey LH, Erland JB, Burris HA 3rd, Spigel DR, et al. Paclitaxel/carboplatin/etoposide versus paclitaxel/topotecan for extensive-stage small cell lung cancer: a Minnie Pearl Cancer Research Network randomized, prospective phase II trial. Oncologist 2005 Oct;10(9):728-33 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16249353.
  16. 16.0 16.1 Leyvraz S, Pampallona S, Martinelli G, Ploner F, Perey L, Aversa S, et al. A threefold dose intensity treatment with ifosfamide, carboplatin, and etoposide for patients with small cell lung cancer: a randomized trial. J Natl Cancer Inst 2008 Apr 16;100(8):533-41 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18398095.
  17. Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, et al. Chemotherapy With or Without Maintenance Sunitinib for Untreated Extensive-Stage Small-Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase II Study-CALGB 30504 (Alliance). J Clin Oncol 2015 Mar 2 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25732163.
  18. 18.0 18.1 Han JY, Kim HT, Lim KY, Yoon SJ, Lee DH, Lee JS. Randomized phase II study of maintenance irinotecan therapy versus observation following induction chemotherapy with irinotecan and cisplatin in extensive disease small cell lung cancer. J Thorac Oncol 2008 Sep;3(9):1039-45 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18758308.
  19. 19.0 19.1 Hanna NH, Sandier AB, Loehrer PJ Sr, Ansari R, Jung SH, Lane K, et al. Maintenance daily oral etoposide versus no further therapy following induction chemotherapy with etoposide plus ifosfamide plus cisplatin in extensive small-cell lung cancer: a Hoosier Oncology Group randomized study. Ann Oncol 2002 Jan;13(1):95-102 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11863118.
  20. 20.0 20.1 Lee SM, Woll PJ, Rudd R, Ferry D, O'Brien M, Middleton G, et al. Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst 2009 Aug 5;101(15):1049-57 Abstract available at HTTP://WWW.NCBI.NLM.NIH.GOV/PUBMED/19608997.

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Appendices

Further resources

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