Current Treatment Options in Oncology

, Volume 13, Issue 4, pp 505–515 | Cite as

Treatment Update in Small-Cell Lung Cancer: From Limited to Extensive Disease

Lung Cancer (HA Wakelee, Section Editor)

Opinion statement

Small-cell lung cancers are aggressive tumors, often discovered with widespread metastases that include brain involvement. For patients with limited-stage disease, the standard of care is platinum-doublet chemotherapy (often etoposide) with concurrent radiation. Concurrent chemoradiotherapy can be difficult when given upfront, sometimes preventing on-time completion of later chemotherapy cycles. Recent data support giving concurrent chemoradiotherapy following 1 or 2 cycles of chemotherapy alone. For patients with extensive disease, chemotherapy alone remains the standard of care. For patients with limited or extensive disease who achieve clinical benefit from primary therapy, consideration of prophylactic cranial radiation should be made. Despite aggressive use of these treatments, most patients will have life-threatening disease return, sometimes very soon after finishing treatment. For those patients who are candidates for additional systemic treatment, several single-agent options exist, such as topotecan, paclitaxel, or even consideration of retreating with the same initial regimen depending on how effective it was. All patients with SCLC should be considered for clinical trials, because this remains our greatest hope for finding more effective therapies.


Small-cell lung cancer Limited-stage Extensive-stage Chemoradiation 

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    American Cancer Society. Cancer facts and figures 2012; 2012.Google Scholar
  2. 2.
    Stupp R, Monnerat C, Turrisi 3rd AT, et al. Small cell lung cancer: state of the art and future perspectives. Lung Cancer. 2004;45:105–17.PubMedCrossRefGoogle Scholar
  3. 3.
    Govindan R, Page N, Morgensztern D, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol. 2006;24:4539–44.PubMedCrossRefGoogle Scholar
  4. 4.
    Burstein HJ, Gelber S, Guadagnoli E, Weeks JC. Use of alternative medicine by women with early-stage breast cancer. N Engl J Med. 1999;340(22):1733.PubMedCrossRefGoogle Scholar
  5. 5.
    Tanvetyanon T, Bepler G. Beta-carotene in multivitamins and the possible risk of lung cancer among smokers versus former smokers: a meta-analysis and evaluation of national brands. Cancer. 2008;113(1):150.PubMedCrossRefGoogle Scholar
  6. 6.
    Johnson BE. Second lung cancers in patients after treatment for an initial lung cancer. JNCI J Natl Cancer Inst. 1998;90(18):1335–45. doi:10.1093/jnci/90.18.1335.CrossRefGoogle Scholar
  7. 7.
    Pujol JL, Carestia L, Daurès JP. Is there a case for cisplatin in the treatment of small-cell lung cancer? a meta-analysis of randomized trials of a cisplatin-containing regimen versus a regimen without this alkylating agent. Br J Cancer. 2000;83(1):8.PubMedCrossRefGoogle Scholar
  8. 8.•
    Rossi A, Massimo Di Maio, Chiodini P. Carboplatin- or cisplatin-based chemotherapy in first-line treatment of small-cell lung cancer: the COCIS meta-analysis of individual patient data. JCO May 10, 2012:1692–1698. Cisplatin and carboplatin have been extensively studied in non-small cell and small-cell lung cancer. In this modern meta-analysis of multiple randomized SCLC trials the agents were found to be similar in terms of efficacy, with expected differences in toxicities.Google Scholar
  9. 9.
    Fukuoka M, Furuse K, Saijo N, Nishiwaki Y, Ikegami H, Tamura T, Shimoyama M, Suemasu KSO. Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer. J Natl Cancer Inst. 1991;83(12):855.PubMedCrossRefGoogle Scholar
  10. 10.
    Roth BJ, Johnson DH, Einhorn LH, Schacter LP, Cherng NC, Cohen HJ, Crawford J, Randolph JA, Goodlow JL, Broun GO. 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;10(2):282.PubMedGoogle Scholar
  11. 11.
    Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, Fukuoka M, Mori K, Watanabe K, Tamura T, Yamamoto S, Saijo N, Japan Clinical Oncology Group. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. 2002;346(2):85.PubMedCrossRefGoogle Scholar
  12. 12.
    Hanna N, Bunn Jr PA, Langer C, Einhorn L, Guthrie Jr T, Beck T, Ansari R, Ellis P, Byrne M, Morrison M, Hariharan S, Wang B, Sandler A. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. ASOJ Clin Oncol. 2006;24(13):2038.CrossRefGoogle Scholar
  13. 13.
    Lara Jr PN, Natale R, Crowley J, Lenz HJ, Redman MW, Carleton JE, Jett J, Langer CJ, Kuebler JP, Dakhil SR, Chansky K, Gandara D. Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124. Clin Oncol. 2009;27(15):2530.CrossRefGoogle Scholar
  14. 14.
    Zatloukal P, Cardenal F, Szczesna A, Gorbunova V, Moiseyenko V, Zhang X, Cisar L, Soria JC, Domine M, Thomas M. 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;21(9):1810.PubMedCrossRefGoogle Scholar
  15. 15.
    Hermes A, Bergman B, Bremnes R, Ek L, Fluge S, Sederholm C, Sundstrøm S, Thaning L, Vilsvik J, Aasebø U, Sörenson S. Irinotecan plus carboplatin versus oral etoposide plus carboplatin in extensive small-cell lung cancer: a randomized phase III trial. J Clin Oncol. 2008;26(26):4261.PubMedCrossRefGoogle Scholar
  16. 16.
    von Pawel J, Gatzemeier U, Pujol JL, Moreau L, Bildat S, Ranson M, Richardson G, Steppert C, Rivière A, Camlett I, Lane S, Ross G. Phase II comparator study of oral versus intravenous topotecan in patients with chemosensitive small-cell lung cancer. J Clin Oncol. 2001;19(6):1743.Google Scholar
  17. 17.
    Eckardt JR, von Pawel J, Pujol JL, Papai Z, Quoix E, Ardizzoni A, Poulin R, Preston AJ, Dane G, Ross G. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol. 2007;25(15):2086.PubMedCrossRefGoogle Scholar
  18. 18.
    Onoda S, Masuda N, Seto T, Eguchi K, Takiguchi Y, Isobe H, Okamoto H, Ogura T, Yokoyama A, Seki N, Asaka-Amano Y, Harada M, Tagawa A, Kunikane H, Yokoba M, Uematsu K, Kuriyama T, Kuroiwa Y, Watanabe K. Phase II Trial of amrubicin for treatment of refractory or relapsed small-cell lung cancer: Thoracic Oncology Research Group Study 0301. Thoracic Oncology Research Group Study 0301. J Clin Oncol. 2006;24(34):5448.PubMedCrossRefGoogle Scholar
  19. 19.•
    Ettinger DS, Jotte R, Lorigan P, Gupta V, Garbo L, Alemany C, Conkling P, Spigel DR, Dudek AZ, Shah C, Salgia R, McNally R, Renschler MF, Oliver JW. Phase II study of amrubicin as second-line therapy in patients with platinum-refractory small-cell lung cancer. J Clin Oncol. 2010;28:2598–603. Amrubicin has shown great promise in Japanese studies in SCLC, with surprising response rates in patients with sensitive and refractory disease. This was the first study reported in a Western population in patients with refractory disease. Although the response rates were lower than seen in Japanese patients, the rates were among the highest ever reported in the United States.PubMedCrossRefGoogle Scholar
  20. 20.
    Jotte R, Conkling P, Reynolds C, Galsky MD, Klein L, Fitzgibbons JF, McNally R, Renschler MF, Oliver JW. Randomized phase II trial of single-agent amrubicin or topotecan as second-line treatment in patients with small-cell lung cancer sensitive to first-line platinum-based chemotherapy. JCO. 2011;29(3):287–93.CrossRefGoogle Scholar
  21. 21.•
    Jotte R, Von Pawel J, Spigel DR, Socinski MA, O'Brien M, Paschold EH, Mezger J, Steins M, Bosquée L, Bubis JA, Nackaerts K, Trigo Perez JM, Clingan PR, Schuette W, Lorigan P, Reck M, Domine M, Shepherd FA, McNally R, Renschler MF. Randomized phase III trial of amrubicin versus topotecan (Topo) as second-line treatment for small cell lung cancer (SCLC). J Clin Oncol (Meeting Abstracts). 2011;29(15):suppl 7000. This is the definitive phase III trial that failed to demonstrate an OS advantage for amrubicin over topotecan. This was one of the largest SCLC trials ever conducted.There were benefits in refractory patients on planned subset analyses.Google Scholar
  22. 22.
    Horn L, Dahlberg SE, Sandler AB, Dowlati A, Moore DF, Murren JR, Schiller JH. Phase II study of cisplatin plus etoposide and bevacizumab for previously untreated, extensive-stage small-cell lung cancer: Eastern Cooperative Oncology Group Study E3501. J Clin Oncol. 2009;27(35):6006.PubMedCrossRefGoogle Scholar
  23. 23.
    Ready NE, Dudek AZ, Pang HH, Hodgson LD, Graziano SL, Green MR, Vokes EE. Cisplatin, irinotecan, and bevacizumab for untreated extensive-stage small-cell lung cancer: CALGB 30306, a phase II study. J Clin Oncol. 2011;29(33):4436.PubMedCrossRefGoogle Scholar
  24. 24.
    Spigel DR, Greco FA, Zubkus JD, Murphy PB, Saez RA, Farley C, Yardley DA, Burris 3rd HA, Hainsworth JD. Phase II trial of irinotecan, carboplatin, and bevacizumab in the treatment of patients with extensive-stage small-cell lung cancer. J Thorac Oncol. 2009;4(12):1555–60.PubMedCrossRefGoogle Scholar
  25. 25.
    Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011;29(16):2215.PubMedCrossRefGoogle Scholar
  26. 26.
    Yu JB, Decker RH, Detterbeck FC, Wilson LD. Surveillance epidemiology and end results evaluation of the role of surgery for stage I small cell lung cancer. J Thorac Oncol. 2010;5(2):215.PubMedCrossRefGoogle Scholar
  27. 27.
    Pignon JP, Arriagada R, Ihde DC, Johnson DH, Perry MC, Souhami RL, Brodin O, Joss RA, Kies MS, Lebeau B. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med. 1992;327(23):1618.PubMedCrossRefGoogle Scholar
  28. 28.
    Warde P, Payne D. Does thoracic irradiation improve survival and local control in limited-stage small-cell carcinoma of the lung? a meta-analysis. J Clin Oncol. 1992;10(6):890.PubMedGoogle Scholar
  29. 29.
    Bonner JA, Sloan JA, Shanahan TG, Brooks BJ, Marks RS, Krook JE, Gerstner JB, Maksymiuk A, Levitt R, Mailliard JA, Tazelaar HD, Hillman S, Jett JR. Phase III comparison of twice-daily split-course irradiation versus once-daily irradiation for patients with limited stage small-cell lung carcinoma. J Clin Oncol. 1999;17(9):2681.PubMedGoogle Scholar
  30. 30.
    Turrisi 3rd AT, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, Wagner H, Aisner S, Johnson DH. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999;340(4):265.PubMedCrossRefGoogle Scholar
  31. 31.
    Murray N, Coy P, Pater JL, Hodson I, Arnold A, Zee BC, Payne D, Kostashuk EC, Evans WK, Dixon P. J Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1993;11(2):336.PubMedGoogle Scholar
  32. 32.
    Pijls-Johannesma MC, De Ruysscher D, Lambin P, Rutten I, Vansteenkiste JF. Early versus late chest radiotherapy for limited stage small cell lung cancer. Cochrane Database Syst Rev. 2005.Google Scholar
  33. 33.••
    Park K, Sun J-M, Kim S-W, Ahn M-j, Ahn JS, Lee DH, Suh C, Ahn YC, Pyo H, Choi EK, Song SY, Lee S-H, Lee JS. Phase III trial of concurrent thoracic radiotherapy (TRT) with either the first cycle or the third cycle of cisplatin and etoposide chemotherapy to determine the optimal timing of TRT for limited-disease small cell lung cancer. J Clin Oncol (Meeting Abstracts). 2012;30(15):suppl 7004. In this modern randomized phase III trial, immediate radiation with concurrent chemotherapy is compared with a delayed strategy and concurrent chemotherapy. The authors report similar efficacy for a delayed strategy, with some improvements in toxicity. This is an important trial, because initial concurrent treatment has been a common recommendation in the United States based on somewhat unclear data from earlier trials.Google Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Lung Cancer Research ProgramSarah Cannon Research InstituteNashvilleUSA

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