Skip to main content

Advertisement

SpringerLink
Log in

Management of small cell lung cancer

  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Small cell lung cancer (SCLC) is an aggressive type of lung cancer characterized by rapid growth and early metastasis. It is chemosensitive and radiosensitive, yet decades of research investigating multimodality treatments have failed to control or cure this disease in most patients. First-line treatment of limited-stage disease consists of chemotherapy (often etoposide/cisplatin or etoposide/carboplatin) combined with thoracic radiation therapy (TRT), followed by prophylactic cranial irradiation to decrease brain metastases as a site of disease progression for those who experience complete remission or a very good partial response to multimodality treatment. In a Japanese trial, the combination of irinotecan and cisplatin had initially shown promise in treating patients with extensive-stage SCLC, but a confirmatory trial in the United States did not find a difference in overall survival with irinotecan/cisplatin versus etoposide/cisplatin. Adding a third drug to the etoposide/cisplatin combination, as well as other triplet therapies, has mostly been ineffective in improving outcomes. Variables in chemotherapy administration, including maintenance therapy, alternating non-cross-resistance regimens, and dose intensification, have not been shown to increase survival at large. In terms of radiation therapy, early administration of TRT concurrent with chemotherapy, and hyperfractionation, have been beneficial in treatment of limited-stage disease. In patients who relapse, second-line therapy options consist of reinduction of previous chemotherapy or administration of a single agent. Targeted biological therapies for SCLC are now being investigated, and although a great deal of research remains to be done, these agents and their derivatives may provide the most hope for future treatment of SCLC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Jemal A, Murray T, Ward E, et al.: Cancer statistics, 2005. CA Cancer J Clin 2005, 55:10–30.

    Article  PubMed  Google Scholar 

  2. Ruckdeschel JC, Schwartz AG, Bepler G, et al.: Cancer of the lung: NSCLC and SCLC. In Atlas of Tumor Pathology, edn 3. Edited by Colby TV, Koss MN, Travis WD. Washington, DC: AFIP; 1994:1655.

    Google Scholar 

  3. von Pawel J, Schiller JH, Shepherd FA, et al.: Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 1999, 17:658–667.

    Google Scholar 

  4. Albain KS, Crowley JJ, LeBlanc M, et al.: Determinants of improved outcome in small-cell lung cancer: an analysis of the 2,580-patient Southwest Oncology Group database. J Clin Oncol 1990, 8:1563–1574.

    PubMed  CAS  Google Scholar 

  5. Kraut M, Wozniak A: Clinical presentation. In Lung Cancer: Principles and Practice, edn 2. Edited by Pass HI. Philadelphia: Lippincott Williams & Wilkins; 2000:522.

    Google Scholar 

  6. Dusmet M, Goldstraw P: Surgery for small cell lung cancer. Hematol Oncol Clin North Am 2004, 18:323–341.

    Article  PubMed  Google Scholar 

  7. Simon GR, Wagner H: Small cell lung cancer. Chest 2003, 123(Suppl):259S-271S.

    Article  PubMed  Google Scholar 

  8. Hauber HP, Bohuslavizki KH, Lund CH, et al.: Positron emission tomography in the staging of small-cell lung cancer: a preliminary study. Chest 2001, 119:950–954.

    Article  PubMed  CAS  Google Scholar 

  9. Schumacher T, Brink I, Mix M, et al.: FDG-PET imaging for the staging and follow-up of small cell lung cancer. Eur J Nucl Med 2001, 28:483–488.

    Article  PubMed  CAS  Google Scholar 

  10. Bradley JD, Dehdashti F, Mintun MA, et al.: Positron emission tomography in limited-stage small-cell lung cancer: a prospective study. J Clin Oncol 2004, 22:3248–3254.

    Article  PubMed  Google Scholar 

  11. Komaki R: Combined treatment for limited small cell lung cancer. Semin Oncol 2003, 30(Suppl 9):56–70.

    Article  PubMed  CAS  Google Scholar 

  12. Murray N, Coy P, Pater JL, et al.: 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, 11:336–344.

    PubMed  CAS  Google Scholar 

  13. Goto K, Nishiwaki Y, Takada M, et al.: Final results of a phase III study of concurrent versus sequential thoracic radiotherapy (TRT) in combination with cisplatin (P) and etoposide (E) for limited-stage small cell lung cancer (LD-SCLC): The Japan Clinical Oncology Group (JCOG) Study [abstract 1805]. http://www.asco.org. Accessed October 14, 2005.

  14. Fried DB, Morris DE, Pool C, et al.: Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage smallcell lung cancer. J Clin Oncol 2004, 22:4837–4845.

    Article  PubMed  Google Scholar 

  15. Turrisi AT, Kim K, Blum R, et al.: 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, 340:265–271.

    Article  PubMed  CAS  Google Scholar 

  16. Bonner JA, Sloan JA, Shanahan TG, et al.: Phase III comparison of twice-daily split-course irradiation versus oncedaily irradiation for patients with limited stage small-cell lung carcinoma. J Clin Oncol 1999, 17:2681–2691.

    PubMed  CAS  Google Scholar 

  17. Takada M, Fukuoka M, Kawahara M, et al.: Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol 2002, 20:3054–3060.

    Article  PubMed  CAS  Google Scholar 

  18. Auperin A, Arriagada R, Pignon JP, et al.: Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission: Prophylactic Irradiation Overview Collaborative Group. N Engl J Med 1999, 341:476–484.

    Article  PubMed  CAS  Google Scholar 

  19. Arriagada R, Le Chevalier T, Borie F, et al.: Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. J Natl Cancer Inst 2004, 87:183–190.

    Article  Google Scholar 

  20. Mascaux C, Paesmans M, Berghman T, et al.: A systematic review of the role of etoposide and cisplatin in the chemotherapy of small-cell lung cancer with methodology assessment and meta-analysis. Lung Cancer 2000, 30:23–36.

    Article  PubMed  CAS  Google Scholar 

  21. Sundstrom S, Bremnes RM, Kaasa S, 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, 20:4665–4672.

    Article  PubMed  CAS  Google Scholar 

  22. Kosmidis PA, Samantas E, Fountzilas G, et al.: Cisplatin/etoposide versus carboplatin/etoposide chemotherapy and irradiation in small cell lung cancer: a randomized phase III study. Hellenic Cooperative Oncology Group for Lung Cancer Trials. Semin Oncol 1994, 21(Suppl 6):23–30.

    PubMed  CAS  Google Scholar 

  23. Noda K, Nishiwaki Y, Kawahara M, et al.: Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med 2002, 346:85–91.

    Article  PubMed  CAS  Google Scholar 

  24. Hanna NH, Einhorn L, Sandler A, et al.: Randomized, phase III trial comparing irinotecan/cisplatin (IP) with etoposide/cisplatin (EP) in patients (pts) with previously untreated, extensive-stage (ES) small cell lung cancer (SCLC) [abstract LBA 7004]. http://www.asco.org. Accessed October 14, 2005.

  25. Loehrer PJ Sr, Ansari R, Gonin R, et al.: Cisplatin plus etoposide with and without ifosfamide in extensive small-cell lung cancer: a Hoosier Oncology Group study. J Clin Oncol 1995, 13:2594–2599.

    PubMed  CAS  Google Scholar 

  26. Niell HB, Herndon JE, Miller AA, et al.: Randomized phase III intergroup trial of etoposide and cisplatin with or without paclitaxel and granulocyte colonystimulating factor in patients with extensive stage small-cell lung cancer: Cancer and Leukemia Group B Trial 9732. J Clin Oncol 2005, 23:3752–3759.

    Article  PubMed  CAS  Google Scholar 

  27. Chrystal K, Cheong K, Harper P: Chemotherapy of small cell lung cancer: state of the art. Curr Opin Oncol 2004, 16:136–140.

    Article  PubMed  Google Scholar 

  28. Sandler AB: Chemotherapy for small cell lung cancer. Semin Oncol 2003, 30:9–25. This review is comprehensive in its scope of chemotherapeutic agents and administration strategies in limited-stage and extensive-stage SCLC.

    Article  PubMed  CAS  Google Scholar 

  29. Ardizzoni A, Tjan-Heijnen VCG, Postmus PE, et al.: 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, 20:3947–3955.

    Article  PubMed  CAS  Google Scholar 

  30. Lorigan P, Woll PJ, O'Brien MER, et al.: Randomized phase III trial of dose-dense chemotherapy supported by wholeblood hematopoietic progenitors in better-prognosis small-cell lung cancer. J Natl Cancer Inst 2005, 97:666–674.

    Article  PubMed  CAS  Google Scholar 

  31. Tjan-Heijnen VC, Wagener DJ, Postmus PE: An analysis of chemotherapy dose and dose-intensity in small-cell lung cancer: lessons to be drawn. Ann Oncol 2002, 13:1519–1530.

    Article  PubMed  CAS  Google Scholar 

  32. von Pawel J: The role of topotecan in treating small cell lung cancer: second-line treatment. Lung Cancer 2003, 41(Suppl 4):S3-S8.

    Google Scholar 

  33. Ebi NKK, Nishiwaki Y, Hojo F, et al.: Second-line chemotherapy for relapsed small cell lung cancer. Jpn J Clin Oncol 1997, 27:166–171.

    Article  PubMed  CAS  Google Scholar 

  34. Schuette W: Chemotherapy as treatment of primary and recurrent small cell lung cancer. Lung Cancer 2001, 33(Suppl 1):S99-S107.

    Article  PubMed  Google Scholar 

  35. von Pawel J, Gatzemeier U, Pujol JL, et al.: Phase II comparator study of oral and intravenous topotecan in patients with chemosensitive small-cell lung cancer. J Clin Oncol 2001, 19:1743–1749.

    Google Scholar 

  36. Masters GA, Declerck L, Blanke C, et al.: Phase II trial of gemcitabine in refractory or relapsed small-cell lung cancer: Eastern Cooperative Oncology Group Trial 1597. J Clin Oncol 2003, 21:1550–1555.

    Article  PubMed  CAS  Google Scholar 

  37. Van der Lee I, Smit EF, van Putten JW, et al.: Single-agent gemcitabine in patients with resistant small-cell lung cancer. Ann Oncol 2001, 12:557–561.

    Article  PubMed  Google Scholar 

  38. Nakamura H, Azuma M, Miyagi K, et al.: A pilot study of docetaxel (TXT) as salvage chemotherapy in small cell lung cancer (SCLC) [abstract 2872]. http://www.asco.org. Accessed October 14, 2005.

  39. Furuse K, Kubota K, Kawahara M, et al.: Phase II study of vinorelbine in heavily previously treated small cell lung cancer. Oncology 1996, 53:169–172.

    Article  PubMed  CAS  Google Scholar 

  40. Lake D, Johnson E, Herndon J, et al.: Phase II trial of navelbine (NVB) in relapsed small cell lung cancer (SCLC) [abstract 1703]. Proc Am Soc Clin Oncol 1997, 16:473a.

    Google Scholar 

  41. Sandler AB: Irinotecan in small-cell lung cancer: the US experience. Oncology (Williston Park) 2001, 15(Suppl 1):11–12.

    CAS  Google Scholar 

  42. Smit EF, Fokkema E, Biesma B, et al.: A phase II study of paclitaxel in heavily pretreated patients with smallcell lung cancer. Br J Cancer 1998, 77:347–351.

    PubMed  CAS  Google Scholar 

  43. Wakelee H, Kelly K: Novel approaches for the treatment of small cell lung cancer. Hematol Oncol Clin North Am 2004, 18:499–518. This is an excellent review of recent developments and strategies for targeted therapies for SCLC.

    Article  PubMed  Google Scholar 

  44. Shepherd FA, Giaccone G, Seymour L, et al.: Prospective, randomized, double-blind, placebo-controlled trial of marimastat after response to first-line chemotherapy in patients with small-cell lung cancer: a trial of the National Cancer Institute of Canada-Clinical Trials Group and the European Organization for Research and Treatment of Cancer. J Clin Oncol 2002, 20:4434–4439.

    Article  PubMed  CAS  Google Scholar 

  45. Pandya KJ, Levy DE, Hidalgo M, et al.: A randomized, phase II ECOG trial of two dose levels of temsirolimus (CCI-779) in patients with extensive stage small lung cancer in remission after induction chemotherapy: a preliminary report [abstract 7005]. http://www.asco.org. Accessed October 14, 2005.

  46. Johl J, Chansky K, Lara PN, et al.: The proteasome inhibitor PS-341 (bortezomib) in platinum (plat)-treated extensive-stage small cell lung cancer (ESCLC): a SWOG (0327) phase II trial [abstract 7047]. http://www.asco.org. Accessed October 14, 2005.

  47. Johnson BE, Fisher T, Fisher B, et al.: Phase II study of imatinib in patients with small cell lung cancer. Clin Cancer Res 2003, 9:188–194.

    Google Scholar 

  48. Thompson DS, Hainsworth JD, Spigel DR, et al.: Irinotecan (I), carboplatin (C), and imatinib (IM) in the first-line treatment of extensive-stage small cell lung cancer (SCLC): a phase II trial of the Minnie Pearl Cancer Research Network [abstract 7049]. http://www.asco.org. Accessed October 14, 2005.

  49. Fossella F, McCann J, Tolcher A, et al.: Phase II trial of BB-10901 (huN901-DM1) given weekly for four consecutive weeks every 6 weeks in patients with relapsed SCLC and CD56-positive small cell carcinoma [abstract 7159]. http://www.asco.org. Accessed October 14, 2005.

  50. Cooney MM, Subbiah S, Chapman R, et al.: Phase II trial of maintenance daily oral thalidomide in patients with extensive-stage small cell lung cancer (ES-SCLC) in remission [abstract 7166]. http://www.asco.org. Accessed October 14, 2005.

  51. Raefsky EL, Spigel DR, Greco FA, et al.: Irinotecan (I), carboplatin (C), and radiotherapy (RT) followed by bevacizumab (B) in the treatment of limited-stage small cell lung cancer (SCLC): a phase II trial of the Minnie Pearl Cancer Research Network [abstract 7050]. http://www.asco.org. Accessed October 14, 2005.

  52. Heymach JV, Johnson DH, Khuri FR, et al.: Phase II study of the farnesyl transferase inhibitor R115777 in patients with sensitive relapse small-cell lung cancer. Ann Oncol 2004, 15:1187–1193.

    Article  PubMed  CAS  Google Scholar 

  53. Rudin CM, Otterson GA, Mauer AM, et al.: A pilot trial of G3139, a bcl-2 antisense oligonucleotide, and paclitaxel in patients with chemorefractory small-cell lung cancer. Ann Oncol 2002, 13:539–545.

    Article  PubMed  CAS  Google Scholar 

  54. Rudin C, Kozloff M, Hoffman PC, et al.: Phase I study of G3139, a bcl-2 antisense oligonucleotide, combined with carboplatin and etoposide in patients with small-cell lung cancer. J Clin Oncol 2004, 22:1110–1117.

    Article  PubMed  CAS  Google Scholar 

  55. Grant SC, Kris MG, Houghton AN, et al.: Long survival of patients with small cell lung cancer after adjuvant treatment with the anti-idiotypic antibody BEC2 plus Bacillus Calmette-Guerin. Clin Cancer Res 1999, 5:1319–1323.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, University of Miami and Sylvester Cancer Center, 1475 NW 12th Avenue (D8-4), Suite 3310, 33136, Miami, FL, USA

    Caio Max S. Rocha Lima MD

Authors
  1. Kristen Keon Ciombor MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Caio Max S. Rocha Lima MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ciombor, K.K., Rocha Lima, C.M.S. Management of small cell lung cancer. Curr. Treat. Options in Oncol. 7, 59–68 (2006). https://doi.org/10.1007/s11864-006-0032-7

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11864-006-0032-7

Keywords

Search

Navigation