Skip to main content
SpringerLink
Log in

Management of Small Cell Lung Cancer

Recent Developments for Optimal Care

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Small cell lung cancer (SCLC) represents approximately 13% of all lung cancer diagnoses and the incidence has reduced over the last 20 years. Treatment of SCLC remains challenging because of its rapid growth, early dissemination and development of drug resistance during the course of the disease.

Chemotherapy remains the cornerstone of treatment for limited (LD) and extensive disease (ED), with concurrent chemotherapy and radical thoracic radiotherapy representing the best treatment option for fit patients with LD. Platinum-based chemotherapy is the treatment of choice in fit patients with good organ function, and the radiosensitizing effect of cisplatin is critically important for concurrent chemoradiotherapy in LD. Anthracycline-containing regimens represent a viable alternative for patients where platinum-based chemotherapy is contraindicated.

Patients who relapse or progress after first-line chemotherapy have a very poor prognosis. Second-line therapy may produce a modest clinical benefit. Maintenance chemotherapy has not been shown to convincingly improve outcomes for SCLC. A number of targeted agents have been investigated in LD and ED, mostly in unselected populations, with disappointing results. Prophylactic cranial irradiation has been shown to reduce the incidence of brain metastases and prolong survival for both LD and ED without negative impact on quality of life (QOL) and cognitive function. Ongoing trials will shed some light on the impact of thoracic radiotherapy on QOL, symptom control and survival in ED SCLC patients who benefitted from first-line chemotherapy.

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

Table I
Table II
Table III

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011; 61(2): 69–90

    PubMed  Google Scholar 

  2. 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 Oct1; 24(28): 4539–44

    PubMed  Google Scholar 

  3. Shepherd FA, Crowley J, Van Houtte P, et al. The International Association for the Study of Lung Cancer lung cancer staging project: proposals regarding the clinical staging of small cell lung cancer in the forthcoming (seventh) edition of the tumor, node, metastasis classification for lung cancer. J Thorac Oncol 2007 Dec; 2(12): 1067–77

    PubMed  Google Scholar 

  4. Cheng S, Evans WK, Stys-Norman D, et al. Chemotherapy for relapsed small cell lung cancer: a systematic review and practice guideline. J Thorac Oncol 2007 Apr; 2(4): 348–54

    PubMed  Google Scholar 

  5. O’Brien ME, Ciuleanu TE, Tsekov H, et al. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol 2006 Dec 1; 24(34): 5441–7

    PubMed  Google Scholar 

  6. Sculier JP, Lafitte JJ, Lecomte J, et al. A phase II randomised trial comparing the cisplatin-etoposide combination chemotherapy with or without carboplatin as second-line therapy for small-cell lung cancer. Ann Oncol 2002 Sep; 13(9): 1454–9

    PubMed  CAS  Google Scholar 

  7. 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 Feb; 17(2): 658–67

    Google Scholar 

  8. O’Bryan RM, Crowley JJ, Kim PN, et al. Comparison of etoposide and cisplatin with bis-chloro-ethylnitrosourea, thiotepa, vincristine, and cyclophosphamide for salvage treatment in small cell lung cancer. A Southwest Oncology Group Study. Cancer 1990 Feb 15; 65(4): 856–60

    Google Scholar 

  9. Giaccone G, Donadio M, Bonardi G, et al. Teniposide in the treatment of small-cell lung cancer: the influence of prior chemotherapy. J Clin Oncol 1988 Aug; 6(8): 1264–70

    PubMed  CAS  Google Scholar 

  10. Evans WK, Feld R, Murray N, et al. 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

    PubMed  CAS  Google Scholar 

  11. Fukuoka M, Furuse K, Saijo N, et al. 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 Jun 19; 83(12): 855–61

    PubMed  CAS  Google Scholar 

  12. Roth BJ, Johnson DH, Einhorn LH, et al. 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

    PubMed  CAS  Google Scholar 

  13. Chute JP, Chen T, Feigal E, et al. Twenty years of phase III trials for patients with extensive-stage small-cell lung cancer: perceptible progress. J Clin Oncol 1999 Jun; 17(6): 1794–801

    PubMed  CAS  Google Scholar 

  14. Pujol JL, Carestia L, Daures 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 Jul; 83(1): 8–15

    PubMed  CAS  Google Scholar 

  15. 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 Dec 15; 20(24): 4665–72

    PubMed  CAS  Google Scholar 

  16. Baka S, Califano R, Ferraldeschi R, et al. 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

    PubMed  CAS  Google Scholar 

  17. Amarasena IU, Walters JA, Wood-Baker R, et al. Platinum versus non-platinum chemotherapy regimens for small cell lung cancer. Cochrane Database Syst Rev 2008 (4): CD006849

  18. Sorensen M, Pijls-Johannesma M, Felip E, Group ObotEGW. Small-cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010 May 1; 21 Suppl. 5: v120–5

    PubMed  Google Scholar 

  19. Simon GR, Turrisi A. Management of small cell lung cancer. Chest 2007 Sep 1; 132 (3 Suppl.): 324–39S

    Google Scholar 

  20. Johnson BE, Crawford J, Downey RJ, et al. Small cell lung cancer clinical practice guidelines in oncology. J Natl Compr Cancer Netw 2006 Jul; 4(6): 602–22

    CAS  Google Scholar 

  21. Einhorn LH, Crawford J, Birch R, et al. Cisplatin plus etoposide consolidation following cyclophosphamide, doxorubicin, and vincristine in limited small-cell lung cancer. J Clin Oncol 1988 Mar; 6(3): 451–6

    PubMed  CAS  Google Scholar 

  22. Spiro SG, Souhami RL, Geddes DM, et al. Duration of chemotherapy in small cell lung cancer: a Cancer Research Campaign trial. Br J Cancer 1989 Apr; 59(4): 578–83

    PubMed  CAS  Google Scholar 

  23. Johnson D, Bass D, Einhorn L, et al. Combination chemotherapy with or without thoracic radiotherapy in limitedstage small-cell lung cancer: a randomized trial of the Southeastern Cancer Study Group. J Clin Oncol 1993 Jul 1; 11(7): 1223–9

    PubMed  CAS  Google Scholar 

  24. Bozcuk H, Artac M, Ozdogan M, et al. Does maintenance/consolidation chemotherapy have a role in the management of small cell lung cancer (SCLC)? Cancer 2005; 104(12): 2650–7

    PubMed  CAS  Google Scholar 

  25. Rossi A, Garassino MC, Cinquini M, et al. Maintenance or consolidation therapy in small-cell lung cancer: a systematic review and meta-analysis. Lung Cancer 2010; 70(2): 119–28

    PubMed  Google Scholar 

  26. Masuda N, Fukuoka M, Kusunoki Y, et al. CPT-11: a new derivative of camptothecin for the treatment of refractory or relapsed small-cell lung cancer. J Clin Oncol 1992 Aug 1; 10(8): 1225–9

    PubMed  CAS  Google Scholar 

  27. Kudoh S, Fujiwara Y, Takada Y, et al. Phase II study of irinotecan combined with cisplatin in patients with previously untreated small-cell lung cancer. West Japan Lung Cancer Group. J Clin Oncol 1998 Mar 1; 16(3): 1068–74

    CAS  Google Scholar 

  28. 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 Jan 10; 346(2): 85–91

    PubMed  CAS  Google Scholar 

  29. Hanna N, Bunn Jr PA, Langer C, et al. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensivestage disease small-cell lung cancer. J Clin Oncol 2006 May 1; 24(13): 2038–43

    PubMed  CAS  Google Scholar 

  30. Lara PN, Natale R, Crowley J, 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

    PubMed  CAS  Google Scholar 

  31. Beutler E, Gelbart T, Demina A. Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc Natl Acad Sci U S A 1998 Jul 7; 95(14): 8170–4

    PubMed  CAS  Google Scholar 

  32. Zatloukal P, Cardenal F, Szczesna A, 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 1; 21(9): 1810–6

    PubMed  CAS  Google Scholar 

  33. Hermes A, Bergman B, Bremnes R, 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

    PubMed  CAS  Google Scholar 

  34. Schmittel A, Sebastian M, Fischer von Weikersthal L, 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

    PubMed  CAS  Google Scholar 

  35. Jiang J, Liang X, Zhou X, 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; 5(6): 867–73

    PubMed  Google Scholar 

  36. Cormier Y, Eisenhauer E, Muldal A, et al. Gemcitabine is an active new agent in previously untreated extensive small cell lung cancer (SCLC). Ann Oncol 1994 Mar 1; 5(3): 283–5

    PubMed  CAS  Google Scholar 

  37. 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 Apr 15; 21(8): 1550–5

    PubMed  CAS  Google Scholar 

  38. Pallis AG, Agelidou A, Agelaki S, et al. A multicenter randomized phase II study of the irinotecan/gemcitabine doublet versus irinotecan monotherapy in previously treated patients with extensive stage small-cell lung cancer. Lung Cancer 2009 Aug; 65(2): 187–91

    PubMed  Google Scholar 

  39. van der Lee I, Smit EF, van Putten JWG, et al. Single-agent gemcitabine in patients with resistant small-cell lung cancer. Ann Oncol 2001 Apr 1; 12(4): 557–61

    PubMed  Google Scholar 

  40. Schuette W, Nagel S, Juergens S, et al. Phase II trial of gemcitabine/irinotecan in refractory or relapsed small-cell lung cancer. Clin Lung Cancer 2005 Sep; 7(2): 133–7

    PubMed  Google Scholar 

  41. Rocha-Lima C, Herndon J, Lee M, et al. Phase II trial of irinotecan/gemcitabine as second-line therapy for relapsed and refractory small-cell lung cancer: Cancer and Leukemia Group B Study 39902. Ann Oncol 2007 Feb 1; 18(2): 331–7

    PubMed  CAS  Google Scholar 

  42. Lee SM, James LE, Qian W, et al. Comparison of gemcitabine and carboplatin versus cisplatin and etoposide for patients with poor-prognosis small cell lung cancer. Thorax 2009 Jan; 64(1): 75–80

    PubMed  CAS  Google Scholar 

  43. Socinski MA, Weissman C, Hart LL, et al. Randomized phase II trial of pemetrexed combined with either cisplatin or carboplatin in untreated extensive-stage small-cell lung cancer. J Clin Oncol 2006 Oct 20; 24(30): 4840–7

    PubMed  CAS  Google Scholar 

  44. Socinski MA, Smit EF, Lorigan P, 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

    PubMed  CAS  Google Scholar 

  45. Ceppi P, Volante M, Ferrero A, et al. Thymidylate synthase expression in gastroenteropancreatic and pulmonary neuroendocrine tumors. Clin Cancer Res 2008 Feb 15; 14(4): 1059–64

    PubMed  CAS  Google Scholar 

  46. Yana T, Negoro S, Takada M, et al. Phase II study of amrubicin in previously untreated patients with extensivedisease small cell lung cancer: West Japan Thoracic Oncology Group (WJTOG) study. Investigational New Drugs 2007; 25(3): 253–8

    PubMed  CAS  Google Scholar 

  47. Onoda S, Masuda N, Seto T, et al. Phase II trial of amrubicin for treatment of refractory or relapsed small-cell lung cancer: Thoracic Oncology Research Group Study 0301. J Clin Oncol 2006 Dec 1; 24(34): 5448–53

    PubMed  CAS  Google Scholar 

  48. Jotte R, Conkling P, Reynolds C, et al. Randomized phase II trial of single-agent amrubicin or topotecan as secondline treatment in patients with small-cell lung cancer sensitive to first-line platinum-based chemotherapy. J Clin Oncol 2011 Jan 20; 29(3): 287–93

    PubMed  CAS  Google Scholar 

  49. Ettinger DS, Jotte R, Lorigan P, et al. Phase II study of amrubicin as second-line therapy in patients with platinumrefractory small-cell lung cancer. J Clin Oncol 2010; 28(15): 2598–603

    PubMed  Google Scholar 

  50. Jotte R, Von Pawel J, Spigel DR, et al. Randomized phase III trial of amrubicin versus topotecan (Topo) as secondline treatment for small cell lung cancer (SCLC). ASCO Meeting Abstracts 2011 Jun 9; 29 (15 Suppl.): 7000

    Google Scholar 

  51. Kobayashi M, Matsui K, Iwamoto Y, et al. Phase II study of sequential triplet chemotherapy, irinotecan and cisplatin followed by amrubicin, in patients with extensive-stage small cell lung cancer. West Japan Thoracic Oncology Group Study 0301. J Thoracic Oncol 2010; 5(7): 1075–80

    Google Scholar 

  52. O’Brien M, Jassem J, Lorigan P, et al. Randomized phase II study (EORTC 08062) of amrubicin as single agent or in combination with cisplatin versus etoposide-cisplatin as first-line treatment in patients (pts) with extensive disease small cell lung cancer (ED SCLC). ASCO Meeting Abstracts 2010 Jun 14; 28 (15 Suppl.): 7052

    Google Scholar 

  53. Onoda S, Masuda N, Seto T, et al. Phase II trial of amrubicin for treatment of refractory or relapsed small-cell lung cancer: Thoracic Oncology Research Group Study 0301. J Clin Oncol 2006 Dec 1; 24(34): 5448–53

    PubMed  CAS  Google Scholar 

  54. Inoue A, Sugawara S, Yamazaki K, et al. Randomized phase II trial comparing amrubicin with topotecan in patients with previously treated small-cell lung cancer: North Japan Lung Cancer Study Group Trial 0402. J Clin Oncol 2008 Nov 20; 26(33): 5401–6

    PubMed  CAS  Google Scholar 

  55. Kato T, Nokihara H, Ohe Y, et al. Phase II trial of amrubicin in patients with previously treated small cell lung cancer (SCLC) [abstract no. 7061]. J Clin Oncol, 2006 ASCO Annual Meeting Proceedings Part I; 2006 Jun 20; 24 (18S Suppl.): 7061

    Google Scholar 

  56. Kawamura-Akiyama Y, Kusaba H, Kanzawa F, et al. Non-cross resistance of ZD0473 in acquired cisplatinresistant lung cancer cell lines. Lung Cancer 2002; 38(1): 43–50

    PubMed  Google Scholar 

  57. Eckardt JR, Bentsion DL, Lipatov ON, et al. Phase II study of picoplatin as second-line therapy for patients with small-cell lung cancer. J Clin Oncol 2009 Apr 20; 27(12): 2046–51

    PubMed  CAS  Google Scholar 

  58. Ciuleanu T, Samarzjia M, Demidchik Y, et al. Randomized phase III study (SPEAR) of picoplatin plus best supportive care (BSC) or BSC alone in patients (pts) with SCLC refractory or progressive within 6 months after first-line platinum-based chemotherapy [abstract no. 7002]. J Clin Oncol 2010 Jun; 28 (15 Suppl.)

  59. Blay J-Y, von Mehren M, Blackstein ME. Perspective on updated treatment guidelines for patients with gastrointestinal stromal tumors. Cancer 2010; 116(22): 5126–37

    PubMed  Google Scholar 

  60. Kaklamani V, O’Regan RM. New targeted therapies in breast cancer. Semin Oncol 2004; 31 (2 Suppl. 4): 20–5

    PubMed  CAS  Google Scholar 

  61. Mok TS, Wu Y-L, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361(10): 947–57

    PubMed  CAS  Google Scholar 

  62. Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011 Jun 30; 364(26): 2507–16

    PubMed  CAS  Google Scholar 

  63. Johnson BE, Fischer T, Fischer B, et al. Phase II study of imatinib in patients with small cell lung cancer. Clin Cancer Res 2003 Dec 1; 9 (16 Pt 1): 5880–7

    PubMed  CAS  Google Scholar 

  64. Krug LM, Crapanzano JP, Azzoli CG, et al. Imatinib mesylate lacks activity in small cell lung carcinoma expressing c-kit protein: a phase II clinical trial. Cancer 2005 May 15; 103(10): 2128–31

    PubMed  CAS  Google Scholar 

  65. Schneider BJ, Gadgeel S, Ramnath N, et al. Phase II trial of imatinib maintenance therapy after irinotecan and cisplatin in patients with c-kit positive extensive-stage small cell lung cancer (ES SCLC). J Clin Oncol 2006 Jun 20; 24 (18 Suppl.): 17089

    Google Scholar 

  66. Johnson FM, Krug LM, Tran HT, et al. Phase I studies of imatinib mesylate combined with cisplatin and irinotecan in patients with small cell lung carcinoma. Cancer 2006 Jan 15; 106(2): 366–74

    PubMed  CAS  Google Scholar 

  67. Moore AM, Einhorn LH, Estes D, et al. Gefitinib in patients with chemo-sensitive and chemo-refractory relapsed small cell cancers: a Hoosier Oncology Group phase II trial. Lung Cancer 2006 Apr; 52(1): 93–7

    PubMed  CAS  Google Scholar 

  68. Macaulay VM, Everard MJ, Teale JD, et al. Autocrine function for insulin-like growth factor I in human small cell lung cancer cell lines and fresh tumor cells. Cancer Res 1990 Apr 15; 50(8): 2511–7

    PubMed  CAS  Google Scholar 

  69. Warshamana-Greene GS, Litz J, Buchdunger E, et al. The insulin-like growth factor-I (IGF-I) receptor kinase inhibitor NVP-ADW742, in combination with STI571, delineates a spectrum of dependence of small cell lung cancer on IGF-I and stem cell factor signaling. Mol Cancer Ther 2004 May; 3(5): 527–35

    PubMed  CAS  Google Scholar 

  70. Lorigan P, Soria J, Stephenson J, et al. Safety and pharmacokinetics of first-line AMG 479 (mab to IGF1R) or AMG 102 (mab to HGF?SF) with platinum-based chemotherapy in extensive stage small cell lung cancer (SCLC). Ann Oncol 2010 Jun; 21 Suppl. 8: viii122–61

    Google Scholar 

  71. Ma PC, Kijima T, Maulik G, et al. c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res 2003 Oct 1; 63(19): 6272–81

    PubMed  CAS  Google Scholar 

  72. Amgen Inc. A phase 1b/2 trial of AMG 479 or AMG 102 in combination with platinum-based chemotherapy as firstline treatment for extensive stage small cell lung cancer [ClinicalTrials.gov identifier NCT00791154]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Jan 4]

  73. Pujol JL, Breton JL, Gervais R, et al. Phase III double-blind, placebo-controlled study of thalidomide in extensivedisease 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

    PubMed  CAS  Google Scholar 

  74. Lee SM, Woll PJ, Rudd R, 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

    PubMed  CAS  Google Scholar 

  75. Patton JF, Spigel DR, Greco FA, et al. Irinotecan (I), carboplatin (C), and radiotherapy (RT) followed by maintenance bevacizumab (B) in the treatment (tx) of limited-stage small cell lung cancer (LS-SCLC): update of a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 2006 Jun 20; 24 (18 Suppl.): 7085

    Google Scholar 

  76. Spigel DR, Hainsworth JD, Farley C, et al. Tracheoesophageal (TE) fistula development in a phase II trial of concurrent chemoradiation (CRT) and bevacizumab (B) in limited-stage small-cell lung cancer (LS-SCLC). J Clin Oncol 2008 May 20; 2 (15 Suppl.): 7554

  77. Sarah Cannon Research Institute. Irinotecan, carboplatin, bevacizumab, and radiation therapy in the treatment of limited stage small cell lung cancer [ClinicalTrials.gov identifier NCT00308529]. US National Institutes of Health, ClincalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Jan 4]

  78. Ready N, Dudek AZ, Wang XF, et al. CALGB 30306: a phase II study of cisplatin (C), irinotecan (I) and bevacizumab (B) for untreated extensive stage small cell lung cancer (ES-SCLC). ASCO Meeting Abstracts 2007 Jun 21; 25 (18 Suppl.): 7563

    Google Scholar 

  79. Spigel DR, Greco FA, Zubkus JD, et al. 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

    PubMed  Google Scholar 

  80. Spigel DR, Townley PM, Waterhouse DM, et al. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensivestage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol 2011 Jun 1; 29(16): 2215–22

    PubMed  CAS  Google Scholar 

  81. Horn L, Dahlberg SE, Sandler AB, et al. 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 Dec 10; 27(35): 6006–11

    PubMed  CAS  Google Scholar 

  82. Ramalingam SS, Mack PC, Vokes EE, et al. Cediranib (AZD2171) for the treatment of recurrent small cell lung cancer (SCLC): a California Consortium phase II study (NCI # 7097). J Clin Oncol 2008 May 20; 26 (15 Suppl.): 8078

    Google Scholar 

  83. Arnold AM, Seymour L, Smylie M, et al. Phase II study of vandetanib or placebo in small-cell lung cancer patients after complete or partial response to induction chemotherapy with or without radiation therapy: National Cancer Institute of Canada Clinical Trials Group Study BR.20. J Clin Oncol 2007 Sep 20; 25(27): 4278–84

    PubMed  CAS  Google Scholar 

  84. Hoosier Oncology Group. Cisplatin and etoposide +/− concurrent vandetanib in previously untreated extensive stage small cell lung cancer [ClinicalTrials.gov identifier NCT00613626]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Jan 4]

  85. Gitlitz BJ, Glisson BS, Moon J, et al. Sorafenib in patients with platinum (plat) treated extensive stage small cell lung cancer (E-SCLC): a SWOG (S0435) phase II trial. J Clin Oncol 2008 May 20; 26 (15 Suppl.): 8039

    Google Scholar 

  86. Park Nicollet Institute. Phase I study of weekly topotecan in combination with sorafenib in treatment of relapsed small cell lung cancer [ClinicalTrials.gov identifier NCT00466232]. US National Institutes of Health, Clin icalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Jan 4]

  87. Southwest Oncology Group. Sorafenib in treating patients with extensive stage small cell lung cancer [ClinicalTrials. gov identifier NCT00182689]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Jan 4]

  88. Leach JW, Swenson K, Anderson E, et al. A phase I study of weekly topotecan (T) in combination with sorafenib (S) for treatment of relapsed or refractory small cell lung cancer (SCLC). ASCO Meeting Abstracts 2010 Jun 14; 28(15Suppl.): e18086

    Google Scholar 

  89. Ready N, Dunphy F, Pang H, et al. Combination chemotherapy with sunitinib (IND 74019; NSC 736511) for untreated extensive-stage small cell lung cancer (SCLC): CALGB 30504 phase IB safety results. ASCO Meeting Abstracts 2010 Jun 14; 28 (15 Suppl.): 7056

    Google Scholar 

  90. Lubiner ET, Spigel DR, Greco FA, et al. Phase II study of irinotecan and carboplatin followed by maintenance sunitinib in the first-line treatment of extensive-stage small cell lung cancer. ASCO Meeting Abstracts 2010 Jun 14; 28 (15 Suppl.): 7049

    Google Scholar 

  91. Schneider BJ, Gadgeel SM, Ramnath N, et al. Phase II trial of sunitinib maintenance therapy after platinum-based chemotherapy in patients with extensive-stage small cell lung cancer (ES SCLC). ASCO Meeting Abstracts 2010 Jun 14; 28 (15 Suppl.): e18041

    Google Scholar 

  92. Yan JJ, Chen FF, Tsai YC, et al. Immunohistochemical detection of Bcl-2 protein in small cell carcinomas. Oncology 1996 Jan–Feb; 53(1): 6–11

    PubMed  CAS  Google Scholar 

  93. Jiang SX, Kameya T, Sato Y, et al. Bcl-2 protein expression in lung cancer and close correlation with neuroendocrine differentiation. Am J Pathol 1996 Mar; 148(3): 837–46

    PubMed  CAS  Google Scholar 

  94. Rudin CM, Salgia R, Wang X, et al. Randomized phase II study of carboplatin and etoposide with or without the bcl-2 antisense oligonucleotide oblimersen for extensivestage small-cell lung cancer: CALGB 30103. J Clin Oncol 2008 Feb 20; 26(6): 870–6

    PubMed  CAS  Google Scholar 

  95. Hann CL, Daniel VC, Sugar EA, et al. Therapeutic efficacy of ABT-737, a selective inhibitor of BCL-2, in small cell lung cancer. Cancer Res 2008 Apr 1; 68(7): 2321–8

    PubMed  CAS  Google Scholar 

  96. Shoemaker AR, Mitten MJ, Adickes J, et al. Activity of the Bcl-2 family inhibitor ABT-263 in a panel of small cell lung cancer xenograft models. Clin Cancer Res 2008 Jun 1; 14(11): 3268–77

    PubMed  CAS  Google Scholar 

  97. Gandhi L, Camidge DR, Ribeiro de Oliveira M, et al. Phase I study of navitoclax (ABT-263), a novel Bcl-2 family inhibitor, in patients with small-cell lung cancer and other solid tumors. J Clin Oncol 2011 Mar 1; 29(7): 909–16

    PubMed  CAS  Google Scholar 

  98. Fossella F, Woll P, Lorigan P, et al. Clinical experience of IMGN901 (BB-10901) in patients with small cell lung carcinoma (SCLC). 13th World Conference on Lung Cancer; 2009 Jul 31–Aug 4; San Francisco (CA)

  99. Woll PJ, O’Brien M, Fossella F, et al. Phase I study of lorvotuzumab mertansine (IMGN901) in patients with CD56-positive solid tumors. Ann Oncol 2010 Oct 1; 21 Suppl. 8: viii175

    Google Scholar 

  100. Antonia SJ, Mirza N, Fricke I, et al. Combination of p53 cancer vaccine with chemotherapy in patients with extensive stage small cell lung cancer. Clin Cancer Res 2006 Feb 1; 12 (3 Pt 1): 878–87

    PubMed  CAS  Google Scholar 

  101. Kusmartsev S, Cheng F, Yu B, et al. All-trans-retinoic acid eliminates immature myeloid cells from tumor-bearing mice and improves the effect of vaccination. Cancer Res 2003 Aug 1; 63(15): 4441–9

    PubMed  CAS  Google Scholar 

  102. H. Lee Moffitt Cancer Center and Research Institute. Vaccine therapy and chemotherapy with or without tretinoin in treating patients with extensive-stage small cell lung cancer [ClinicalTrials.gov identifier NCT00618891]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Jan 5]

  103. Varjosalo M, Taipale J. Hedgehog: functions and mechanisms. Genes Dev 2008 Sep 15; 22(18): 2454–72

    PubMed  CAS  Google Scholar 

  104. Watkins DN, Berman DM, Burkholder SG, et al. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature 2003; 422(6929): 313–7

    PubMed  CAS  Google Scholar 

  105. Eastern Cooperative Oncology Group. Cisplatin and etoposide phosphate with or without GDC-0449 or cixutumumab in treating patients with extensive-stage small cell lung cancer [ClinicalTrials.gov identifier NCT00887159]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Jan 5]

  106. Infinity Pharmaceuticals, Inc. A phase 1 study of IPI-926 in patients with advanced and/or metastatic solid tumor malignancies [ClinicalTrials.gov identifier NCT00761696]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Jan 5]

  107. Bayman NA, Sheikh H, Kularatne B, et al. Radiotherapy for small-cell lung cancer: where are we heading? Lung Cancer 2009; 63(3): 307–14

    PubMed  CAS  Google Scholar 

  108. Turrisi 3rd 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 Jan 28; 340(4): 265–71

    PubMed  CAS  Google Scholar 

  109. De Ruysscher D, Pijls-Johannesma M, Bentzen Sr M, et al. Time between the first day of chemotherapy and the last day of chest radiation is the most important predictor of survival in limited-disease small-cell lung cancer. J Clin Oncol 2006 Mar 1; 24(7): 1057–63

    PubMed  Google Scholar 

  110. Baas P, Belderbos JSA, Senan S, et al. Concurrent chemotherapy (carboplatin, paclitaxel, etoposide) and involvedfield radiotherapy in limited stage small cell lung cancer: a Dutch multicenter phase II study. Br J Cancer 2006; 94(5): 625–30

    PubMed  CAS  Google Scholar 

  111. De Ruysscher D, Bremer R-H, Koppe F, et al. Omission of elective node irradiation on basis of CT-scans in patients with limited disease small cell lung cancer: a phase II trial. Radiother Oncol 2006; 80(3): 307–12

    PubMed  Google Scholar 

  112. van Loon J, De Ruysscher D, Wanders R, et al. Selective nodal irradiation on basis of 18FDG-PET scans in limiteddisease small-cell lung cancer: a prospective study. Int J Radiat Oncol Biol Phys 2010; 77(2): 329–36

    PubMed  Google Scholar 

  113. Auperin A, Arriagada R, Pignon J-P, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med 1999; 341(7): 476–84

    PubMed  CAS  Google Scholar 

  114. Le Péchoux C, Dunant A, Senan S, et al. Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212, and IFCT 99-01): a randomised clinical trial. Lancet Oncol 2009; 10(5): 467–74

    PubMed  Google Scholar 

  115. Le Péchoux C, Laplanche A, Faivre-Finn C, et al. Clinical neurological outcome and quality of life among patients with limited small-cell cancer treated with two different doses of prophylactic cranial irradiation in the intergroup phase III trial (PCI99-01, EORTC 22003-08004, RTOG 0212 and IFCT 99-01). Ann Oncol 2011 May; 22(5): 1154–63

    PubMed  Google Scholar 

  116. Slotman B, Faivre-Finn C, Kramer G, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 2007 Aug 16; 357(7): 664–72

    PubMed  CAS  Google Scholar 

  117. Slotman BJ, Mauer ME, Bottomley A, et al. Prophylactic cranial irradiation in extensive disease small-cell lung cancer: short-term health-related quality of life and patient reported symptoms, results of an international phase III randomized controlled trial by the EORTC radiation oncology and lung cancer groups. J Clin Oncol 2009 Jan 1; 27(1): 78–84

    PubMed  Google Scholar 

  118. Jeremic B, Shibamoto Y, Nikolic N, et al. Role of radiation therapy in the combined-modality treatment of patients with extensive disease small-cell lung cancer: a randomized study. J Clin Oncol 1999 Jul 1; 17(7): 2092–9

    PubMed  CAS  Google Scholar 

  119. VU University Medical Center, Department of Radiation Oncology. Randomised trial on chest irradiation in extensive disease small cell lung cancer. Nederlands Trial Register identifier NTR1527 [online]. Available from URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1527 [Accessed 2012 Jan 26]

  120. Gore E. Randomized phase II study comparing prophylactic cranial irradiation alone to prophylactic cranial irradiation and consolidative extra-cranial irradiation for extensive disease small cell lung cancer (ED-SCLC) [online]. Available from URL: http://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=0937 [Accessed 2012 Jan 26]

Download references

Acknowledgements

No sources of funding were used to conduct this study or prepare this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK

    Raffaele Califano MD, Aidalena Z. Abidin, Rahul Peck & Paul Lorigan

  2. Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK

    Corinne Faivre-Finn

Authors
  1. Raffaele Califano MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aidalena Z. Abidin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rahul Peck
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Corinne Faivre-Finn
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paul Lorigan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Raffaele Califano MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Califano, R., Abidin, A.Z., Peck, R. et al. Management of Small Cell Lung Cancer. Drugs 72, 471–490 (2012). https://doi.org/10.2165/11597640-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11597640-000000000-00000

Keywords

Search

Navigation