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Modern Management of Small-Cell Lung Cancer

  • Therapy in Practice
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Abstract

In this article, we review best standard practice for the management of small-cell lung cancer (SCLC) and indicate the likely areas of development over the next 5–10 years. A number of prognostic scores have been developed and these allow more rational decisions on treatment.

Treatment with cisplatin plus etoposide with early, concurrent radiotherapy is the standard of care for patients with limited-stage disease (LD) suitable for this approach. A 5-year survival rate of 25% has been reported for concurrent hyperfractionated radiotherapy; however, the applicability of this in most busy hospitals is uncertain and this treatment is currently being compared with a high-dose, once-daily regimen. Patients unsuitable for concurrent chemo-radiotherapy are treated with a sequential approach. Patients with LD responding to treatment should be offered prophylactic cranial irradiation (PCI). A variety of strategies for improving survival have been investigated. Intensification of chemotherapy has not shown any clear survival advantage, but maintenance of dose intensity in patients with good prognosis is important. The evidence around maintenance therapy is conflicting and this is not routinely used.

Patients with extensive-stage disease but few other adverse prognostic factors should be treated with a platinum compound plus etoposide, and carboplatin is a reasonable choice. Responding patients should be offered PCI as this is associated with a survival benefit. The initial positive results for irinotecan have not been repeated in a larger study. Age is not a prognostic factor, but caution needs to be exercised as prognostic scores do not reflect co-morbidity.

Patients with relapsed disease have a poor prognosis, but there is evidence of a survival benefit for salvage chemotherapy in those fit for treatment. The choice of treatment will depend on a number of factors, including the disease-free interval. Topotecan is the only drug licensed in this indication, but myelosuppression is considerable.

A number of new drugs are under evaluation and showing promise in SCLC. One of the most promising of these is amrubicin. A large randomised study has failed to show any benefit from the addition of thalidomide to chemotherapy with carboplatin and etoposide in extensive-stage disease patients responding to chemotherapy. Studies of a number of targeted treatments are also ongoing. The challenge for the future is to identify new targets, overcome drug-resistance mechanisms and redundancy in biological systems, and incorporate these new treatments into concurrent chemo-radiotherapy schedules.

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References

  1. 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(28): 4539–44

    Article  PubMed  Google Scholar 

  2. Zelen M. Keynote address on biostatistics and data retrieval. Cancer Chemother Rep 3 1973; 4(2): 31–42

    PubMed  CAS  Google Scholar 

  3. Stahel RA, Ginsberg R, Havemann K, et al. Staging and prognostic factors in small cell lung cancer: a consensus report. Lung Cancer 1989; 5: 119–26

    Article  Google Scholar 

  4. Mountain CF. A new international staging system for lung cancer. Chest 1986; 89 (4 Suppl.): 225–233S

    Google Scholar 

  5. Micke P, Faldum A, Metz T, et al. Staging small cell lung cancer. Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer: what limits limited disease? Lung Cancer 2002; 37(3): 271–6

    Google Scholar 

  6. Cerny T, Blair V, Anderson H, et al. Pretreatment prognostic factors and scoring system in 407 small cell lung cancer patients. Int J Cancer 1987; 39(2): 146–9

    Article  PubMed  CAS  Google Scholar 

  7. Rawson MS, Peto J. An overview of prognostic factors in small cell lung cancer: a report from the Subcommittee for the Management of Lung Cancer of the United Kingdom Coordinating Committee on Cancer Research. Br J Cancer 1990; 61(4): 597–604

    Article  PubMed  CAS  Google Scholar 

  8. Sagman U, Maki E, Evans WK, et al. Small cell carcinoma of the lung: derivation of a prognostic staging score. J Clin Oncol 1991; 9(9): 1639–49

    PubMed  CAS  Google Scholar 

  9. Thatcher N, Anderson H, Burt P, et al. The value of anatomic staging and other prognostic factors in small cell lung cancer management: a view of European studies. Semin Radiat Oncol 1995; 5(1): 19–26

    Article  PubMed  Google Scholar 

  10. Paesmans M, Sculier JP, Lecomte J, et al. Prognostic factors for patients with small cell lung cancer: analysis of a series of 763 patients included in 4 consecutive prospective clinical trials with a minimum follow-up of 5 years. Cancer 2000; 89(3): 523–33

    Article  PubMed  CAS  Google Scholar 

  11. Albain KS, Crowley JJ, LeBlanc M. Survival determinants in extensive stage small cell lung cancer: the Southwest Oncology Group Experience. J Clin Oncol 1991; 9(9): 1618–26

    PubMed  CAS  Google Scholar 

  12. Jänne P, Freidlin B, Saxman S, et al. Twenty-five years of clinical research for patients with limited-stage small cell lung carcinoma in North America. Cancer 2002; 95(7): 1528–38

    Article  PubMed  Google Scholar 

  13. Roth BJ, Johnson DH, Einhorn LH, et al. Randomised study of cyclophosphamide, doxorubicin and vincristine versus etoposide and cisplatin versus alternation of these 2 regimens in extensive stage small cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol 1992; 10(2): 282–91

    PubMed  CAS  Google Scholar 

  14. Evans WK, Feld R, Murray N, et al. Superiority of alternating non-cross-resistant chemotherapy in extensive stage small cell lung cancer: a multi-centre, randomised clinical trial by the National Cancer Institute of Canada. Ann Intern Med 1987; 107(4): 451–8

    PubMed  CAS  Google Scholar 

  15. Fukuoka M, Furuse K, Saijo N, et al. Randomised trial of cyclophosphamide, doxorubicin and vincristine versus cisplatin and etoposide versus alternation of these regimens in small cell lung cancer. J Nat Cancer Inst 1991; 83(12): 855–61

    Article  PubMed  CAS  Google Scholar 

  16. 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 randomised phase III trial with 5 years’ follow up. J Clin Oncol 2002; 20(24): 4665–72

    Article  PubMed  CAS  Google Scholar 

  17. 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; 17(6): 1794–801

    PubMed  CAS  Google Scholar 

  18. Pujol JL, Carestia L, Daures J. Is there a case for cisplatin in the treatment of small cell lung cancer? A meta analysis of randomised trials of a cisplatin-containing regimen versus a regimen without this alkylating agent. Br J Cancer 2000; 83(1): 8–15

    Article  PubMed  CAS  Google Scholar 

  19. Thatcher N, Qian W, Clark PI, et al. Ifosfamide, carboplatin, and etoposide with midcycle vincristine versus standard chemotherapy in patients with small-cell lung cancer and good performance status: clinical and quality-of-life results of the British Medical Research Council multicenter randomized LU21 trial. J Clin Oncol 2005; 23(33): 8371–9

    Article  PubMed  CAS  Google Scholar 

  20. Brahmer JR, Ettinger DS. Carboplatin in the treatment of small cell lung cancer. Oncologist 1998; 3(3): 143–54

    PubMed  CAS  Google Scholar 

  21. Kosmidis PA, Samantas E, Fountzilas G, et al. Cisplatin/etopo-side 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 (3 Suppl. 6): 23–30

    PubMed  CAS  Google Scholar 

  22. Loehrer Sr PJ, Ansari R, Gonin R, et al. Cisplatin plus etoposide with or without ifosfamide in extensive stage small cell lung cancer: a Hoosier Oncology Group study. J Clin Oncol 1995; 13(10): 2594–9

    CAS  Google Scholar 

  23. Postmus P, Smit EF, Kirkpatrick A, et al. Testing the possible non-cross resistance of two equipotent combination chemotherapy regimens against small-cell lung cancer: a phase II study of the EORTC Lung Cancer Cooperative Group. Eur J Cancer 1993; 29A(2): 204–7

    Article  PubMed  CAS  Google Scholar 

  24. Sculier J, Berghmans T, Castaigne C, et al. Maintenance chemotherapy for small cell lung cancer: a critical review of the literature. Lung Cancer 1998; 19(2): 141–51

    Article  PubMed  CAS  Google Scholar 

  25. Bozcuk H, Artac M, Ozdogan M, et al. Does maintenance/consolidation chemotherapy have a role in the management of small cell lung cancer (SCLC)? A meta-analysis of the published randomized controlled trials. Cancer 2005; 104(12): 2650–7

    Article  PubMed  CAS  Google Scholar 

  26. Cohen MH, Creaven PJ, Fossieck Jr BE, et al. Intensive chemotherapy of small cell bronchogenic carcinoma. Cancer Treat Rep 1977; 61(3): 349–54

    PubMed  CAS  Google Scholar 

  27. Arriagada R, Le Chevalier T, Pignon JP, et al. Initial chemother-apeutic doses and survival in patients with limited small-cell lung cancer. N Engl J Med 1993; 329(25): 1848–52

    Article  PubMed  CAS  Google Scholar 

  28. Ettinger DS, Finkelstein DM, Abeloff MD, et al. A randomized comparison of standard chemotherapy versus alternating chemotherapy and maintenance versus no maintenance therapy for extensive-stage small-cell lung cancer: a phase III study of the Eastern Cooperative Oncology Group. J Clin Oncol 1990; 8(2): 230–40

    PubMed  CAS  Google Scholar 

  29. Cullen M, Morgan D, Gregory W, et al. Maintenance chemotherapy for anaplastic small cell carcinoma of the bronchus: a randomised, controlled trial. Cancer Chemother Pharmacol 1986; 17(2): 157–60

    Article  PubMed  CAS  Google Scholar 

  30. Medical Research Council. Controlled trial of twelve versus six courses of chemotherapy in the treatment of small-cell lung cancer: report to the Medical Research Council by its Lung Cancer Working Party. Br J Cancer 1989; 59(4): 584–90

    Article  Google Scholar 

  31. Giaccone G, Dalesio O, Mc Vie G, et al. Maintenance chemotherapy in small-cell lung cancer: long-term results of a randomized trial. European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol 1993; 11(7): 1230–40

    PubMed  CAS  Google Scholar 

  32. 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; 59(4): 578–83

    Article  PubMed  CAS  Google Scholar 

  33. Lebeau B, Chastang C, Allard P, et al. Six versus twelve cycles for complete responders to chemotherapy in small cell lung cancer: definitive results of a randomized clinical trial. The “Petites Cellules” Group. EurRespir J 1992; 5(3): 286–90

    CAS  Google Scholar 

  34. Crawford J, Ozer H, Stoller R, et al. Reduction by granulocyte colony stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N Engl J Med 1991; 325(3): 164–70

    Article  PubMed  CAS  Google Scholar 

  35. Trillet-Lenoir V, Green J, Manegold C, et al. Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy. Eur J Cancer 1993; 29A(3): 319–24

    Article  PubMed  CAS  Google Scholar 

  36. Fukuoka M, Masuda N, Negoro S, et al. CODE chemotherapy with and without granulocyte colony-stimulating factor in small-cell lung cancer. Br J Cancer 1997; 75(2): 306–9

    Article  PubMed  CAS  Google Scholar 

  37. Woll PJ, Hodgetts J, Lomax L, et al. Can cytotoxic dose-intensity be increased by using granulocyte colony-stimulating factor? A randomised controlled trial of lenograstim in small cell lung cancer. J Clin Oncol 1995; 13(3): 652–9

    PubMed  CAS  Google Scholar 

  38. Steward WP, von Pawel J, Gatzemeier U, et al. Effects of granulocyte-macrophage colony-stimulating factor and dose intensification of V-ICE chemotherapy in small-cell lung cancer: a prospective randomised study of 300 patients. J Clin Oncol 1998; 16(2): 642–50

    PubMed  CAS  Google Scholar 

  39. Thatcher N, Girling DJ, Hopwood P, et al. Improving survival without reducing quality of life in small-cell lung cancer patients by increasing the dose-intensity of chemotherapy with granulocyte colony-stimulating factor support: results of a British Medical Research Council Multicenter Randomized Trial. Medical Research Council Lung Cancer Working Party. J Clin Oncol 2000; 18(2): 395–404

    CAS  Google Scholar 

  40. James LE, Gower NH, Rudd RM, et al. A randomised trial of low-dose/high-frequency chemotherapy as palliative treatment of poor-prognosis small-cell lung cancer: a Cancer Research Campaign trial. Br J Cancer 1996; 73(12): 1563–8

    Article  PubMed  CAS  Google Scholar 

  41. Pujol JL, Douillard JY, Riviere A, et al. Dose intensity with four drug chemotherapy regimen with or without recombinant human granulocyte-macrophage colony stimulating factor in extensive stage small-cell lung cancer: a multi-centre randomised phase III trial. J Clin Oncol 1997; 15(5): 2082–9

    PubMed  CAS  Google Scholar 

  42. Ardizzoni A, Tjan-Heijnen VC, Postmus PF, et al. Standard versus intensified chemotherapy with granulocyte colony-stimulating factor support in small cell lung cancer: a prospective European Organisation for Research and Treatment of Cancer-Lung Cancer Group Phase III trial-08923. J Clin Oncol 2002; 20(19): 3947–55

    Article  PubMed  CAS  Google Scholar 

  43. Lorigan P, Woll PJ, O’Brien ME, et al. Randomised phase III trial of dose-dense chemotherapy supported by whole-blood haematopoietic progenitors in better prognosis small cell lung cancer. J Natl Cancer Inst 2005; 97(9): 666–74

    Article  PubMed  CAS  Google Scholar 

  44. Buchholz E, Manegold C, Pilz L, et al. Standard versus dose-intensified chemotherapy with sequential reinfusion of hema-topoietic progenitor cells in small cell lung cancer patients with favorable prognosis. J Thorac Surg 2007; 2(1): 51–8

    Google Scholar 

  45. Humblet Y, Symann M, Bosly A, et al. Late intensification chemotherapy with autologous bone marrow transplantation in selected small-cell carcinoma of the lung: a randomized study. J Clin Oncol 1987; 5: 1864–73

    PubMed  CAS  Google Scholar 

  46. Leyvraz S, Pampallona S, Martinelli G, et al. Randomized phase III study of high-dose sequential chemotherapy (CT) supported by peripheral blood progenitor cells (PBPC) for the treatment of small cell lung cancer (SCLC): results of the EBMT Random-ICE trial [abstract no. 7064]. 42nd Annual Meeting of the American Society of Clinical Oncology; 2006 Jun 2–6; Atlanta (GA)

  47. Slotman B, Faivre-Finn C, Kramer GWPM, et al. Randomized trial on the use of prophylactic cranial irradiation in extensive disease small cell lung cancer (EORTC 08993-22993) [abstract no. 4]. J Clin Oncol 2007; 25: 18s

    Google Scholar 

  48. Siu LL, Shepherd FA, Murray N, et al. Influence of age on the treatment of limited stage small cell lung cancer. J Clin Oncol 1996; 14(3): 821–8

    PubMed  CAS  Google Scholar 

  49. Dajczman E, Fu LY, Small R, et al. Treatment of small cell lung cancer in the elderly. Cancer 1996; 77(10): 2032–8

    Article  PubMed  CAS  Google Scholar 

  50. Nou E. Full chemotherapy in elderly patients with small cell bronchial carcinoma. Acta Oncol 1996; 35(4): 399–406

    Article  PubMed  CAS  Google Scholar 

  51. Jara C, Gomez-Aldaravi JL, Tirado R, et al. Small cell lung cancer in the elderly: is age a patient relevant factor? Acta Oncol 1999; 38(6): 781–6

    Article  PubMed  CAS  Google Scholar 

  52. Yuen AR, Zou G, Turrisi AT, et al. Similar outcome of elderly patients in intergroup trial 0096: cisplatin, etoposide, and thoracic radiotherapy administered once or twice daily in limited stage small cell lung carcinoma. Cancer 2000; 89(9): 1853–8

    Article  Google Scholar 

  53. Gridelli C, De Vivo R, Monfardini S. Management of SCLC in the elderly. Crit Rev Oncol Haematol 2002; 4(1): 79–88

    Article  Google Scholar 

  54. Ludbrook JJ, Truong PT, MacNeil MV, et al. Do age and comorbidity impact treatment allocation and outcomes in limited stage small-cell lung cancer? A community-based population analysis. Int J Radiat Oncol Biol Phys 2003; 55(5): 1321–30

    Article  PubMed  Google Scholar 

  55. Brown JS, Eraut D, Trask C, et al. Age and treatment of lung cancer. Thorax 1996; 51(6): 564–8

    Article  PubMed  CAS  Google Scholar 

  56. Radford JA, Ryder WD, Dodwell D, et al. Predicting septic complications of chemotherapy: an analysis of 382 patients treated for small cell lung cancer without dose reduction after major sepsis. Eur J Cancer 1993; 29A(1): 81–6

    Article  Google Scholar 

  57. Lassen UN, Osterlind K, Hirsch FR, et al. Early death during chemotherapy in patients with small-cell lung cancer: derivation of a prognostic index for toxic death and progression. Br J Cancer 1999; 79(3-4): 515–9

    Article  PubMed  CAS  Google Scholar 

  58. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40(5): 373–83

    Article  PubMed  CAS  Google Scholar 

  59. Miller MD, Paradis CF, Houck PR, et al. Rating chronic medical illness burden in geropsychiatric practice and research: application of the Cumulative Illness Rating Scale. Psychiatry Res 1992 Mar; 41(3): 237–48

    Article  PubMed  CAS  Google Scholar 

  60. Katz S, Ford AB, Moskowitz RW, et al. Studies of illness in the aged: the index of ADL. A standardized measure of biological and psychosocial function. JAMA 1963 Sep 21; 185: 914–9

    Article  PubMed  CAS  Google Scholar 

  61. Lawton MP, Brody EM. Assessment of older patients. Gerontologist 1969; 9(3): 179–86

    Article  PubMed  CAS  Google Scholar 

  62. Lawton MP, Moss M, Fulcomer M, et al. A research and service orientated multilevel assessment instrument. J Gerontol 1982; 37(1): 91–9

    PubMed  CAS  Google Scholar 

  63. Extermann M, Overcash J, Lyman GH, et al. Comorbidity and functional status are independent in older cancer patients. J Clin Oncol 1998; 16(4): 1582–7

    PubMed  CAS  Google Scholar 

  64. Murray N, Grafton C, Shah A, et al. Abbreviated treatment for elderly, infirm or non-compliant patients with limited-stage small cell lung cancer. J Clin Oncol 1998; 16(10): 3323–8

    PubMed  CAS  Google Scholar 

  65. Westeel V, Murray N, Gelmon K, et al. New combination of old drugs for elderly patients with small cell lung cancer: a phase II study of the PAVE regimen. J Clin Oncol 1998; 16(5): 1940–7

    PubMed  CAS  Google Scholar 

  66. Earl HM, Rudd RM, Spiro SG, et al. A randomised trial of planned versus as required chemotherapy in small cell lung cancer: a Cancer Research Campaign trial. Br J Cancer 1991 Sep; 64(3): 566–72

    Article  PubMed  CAS  Google Scholar 

  67. Medical Research Council Lung Cancer Working Group Party. Randomised trial of four-drug vs less intensive two-drug chemotherapy in the palliative treatment of patients with small-cell lung cancer (SCLC) and poor prognosis. Br J Cancer 1996; 73(3): 406–13

    Article  Google Scholar 

  68. Girling DJ. Comparison of oral etoposide and standard intravenous multidrug chemotherapy for small-cell lung cancer: a stopped multicentre randomised trial. Medical Research Council Lung Cancer Working Party. Lancet 1996; 348(9027): 563–6

    Article  PubMed  CAS  Google Scholar 

  69. Souhami RL, Spiro SG, Rudd RM, et al. Five-day oral etoposide treatment for advanced small-cell lung cancer: randomized comparison with intravenous chemotherapy. J Natl Cancer Inst 1997; 89(8): 577–80

    Article  PubMed  CAS  Google Scholar 

  70. White SC, Lorigan P, Middleton MR, et al. Randomised phase II study of cyclophosphamide, doxorubicin and vincristine compared with single agent carboplatin in patients with poor prognosis small cell lung cancer. Cancer 2001; 92(3): 601–8

    Article  PubMed  CAS  Google Scholar 

  71. Albain KS, Crowley JJ, Hutchins L. Predictors of survival following relapse or progression of small cell lung cancer: Southwest Oncology Group Study 8605 report and analysis of recurrent disease data base. Cancer 1993 Aug 15; 72(4): 1184–91

    Article  PubMed  CAS  Google Scholar 

  72. Vincent M, Evans B, Smith I. First line chemotherapy rechallenge after relapse in small cell lung cancer. Cancer Chemother Pharmacol 1988; 21(1): 45–8

    Article  PubMed  CAS  Google Scholar 

  73. Postmus PE, Berendsen H, van Zandwijk N, et al. 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; 23(9): 1409–11

    Article  PubMed  CAS  Google Scholar 

  74. Ardizzoni A, Hansen H, Dombernowsky P, et al. Topotecan, a new active drug in the second-line treatment of small-cell lung cancer: a phase II study in patients with refractory and sensitive disease. The European Organization for Research and Treatment of Cancer Early Clinical Studies Group and New Drug Development Office, and the Lung Cancer Cooperative Group. J Clin Oncol 1997; 15(5): 2090–6

    PubMed  CAS  Google Scholar 

  75. Eckardt J, Gralla R, Palmer MC, et al. Topotecan (T) as second-line therapy in patients (Pts) with small cell lung cancer (SCLC): a phase II study [abstract]. Ann Oncol 1996; 7 Suppl. 5: 107

    Article  Google Scholar 

  76. Depierre A, von Pawel J, Hans K, et al. Evaluation of topotecan (Hycamtin™) in relapsed small cell lung cancer (SCLC): a multicenter phase II study [abstract]. Lung Cancer 1997; 18 Suppl. 1: 35

    Article  Google Scholar 

  77. von Pawel J, Depierre A, Hans K, et al. Topotecan (Hycamtin™) in small cell lung cancer (SCLC) after failure of first line therapy: multicentre phase II study [abstract]. Eur J Cancer 1997; 33 Suppl. 18: S229

    Article  Google Scholar 

  78. 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; 24(34): 5441–7

    Article  PubMed  CAS  Google Scholar 

  79. 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(2): 658–67

    Google Scholar 

  80. von Pawel J, Gatzemeier U, Pujol J, et al. Phase II comparator study of oral versus intravenous topotecan in patients with chemosensitive small-cell lung cancer. J Clin Oncol 2001; 19(6): 1743–9

    Google Scholar 

  81. Eckardt JR, von Pawel J, Hainsworth J, et al. Single agent oral topotecan versus intravenous topotecan in patients with chemosensitive small cell lung cancer [abstract no. 2488]. 39th Annual Meeting of the American Society of Clinical Oncology; 2003 May 31-Jun 3; Chicago (IL)

  82. Bahadori HR, Green MR, Catapano CV. Synergistic interaction between topotecan and microtubule-interfering agents. Cancer Chemother Pharmacol 2001; 48(3): 188–96

    Article  PubMed  CAS  Google Scholar 

  83. Nagourney RA, Sommers BL, Harper SM, et al. Ex vivo analysis of topotecan: advancing the application of laboratory-based clinical therapeutics. Br J Cancer 2003; 89(9): 1789–95

    Article  PubMed  CAS  Google Scholar 

  84. Jonsson E, Fridborg H, Nygren P, et al. Synergistic interactions of combinations of topotecan with standard drugs in primary cultures of human tumor cells from patients. Eur J Clin Pharmacol 1998; 54(7): 509–14

    Article  PubMed  CAS  Google Scholar 

  85. Eckardt JR, von Pawel J, Papai Z, et al. Open-label, multicenter, randomized, phase III study comparing oral topotecan/cisplatin versus etoposide/cisplatin as treatment for chemotherapynaive patients with extensive-disease small-cell lung cancer. J Clin Oncol 2006; 24(13): 2044–51

    Article  PubMed  CAS  Google Scholar 

  86. Schiller JH, Adak S, Cella D, et al. Topotecan versus observation after cisplatin plus etoposide in extensive-stage small-cell lung cancer: E7593. A phase III trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2001; 19(8): 2114–22

    CAS  Google Scholar 

  87. 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. J Clin Oncol 1998; 16(3): 1068–74

    PubMed  CAS  Google Scholar 

  88. Noda K, Nishiwaki Y, Kawahara M, et al. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive stage small-cell lung cancer. New Engl J Med 2002; 346(2): 85–91

    Article  PubMed  CAS  Google Scholar 

  89. Hanna N, Bunn PA, Langer C, 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; 24(13): 2038–43

    Article  PubMed  CAS  Google Scholar 

  90. Hermes A, Bergman B, Bremmes R, et al. A randomised phase III trial of irinotecan and carboplatin versus etopside and carboplatin in patients with ED SCLC [abstract no. 7523]. J Clin Oncol 2007; 25: 18s

    Google Scholar 

  91. Ettinger DS, Finkelstein DM, Sarma RP, et al. Phase II study of paclitaxel in patients with extensive-disease small-cell lung cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol 1995; 13(6): 1430–5

    PubMed  CAS  Google Scholar 

  92. Kirschling RJ, Grill JP, Marks RS. Paclitaxel and G-CSF in previously untreated patients with extensive stage small-cell lung cancer: a phase II study of the North Central Cancer Treatment Group. Am J Clin Oncol 1999; 22(5): 517–22

    PubMed  CAS  Google Scholar 

  93. Greco FA, Hainsworth JD. Paclitaxel, carboplatin, and oral etoposide in the treatment of small cell lung cancer. Semin Oncol 1996; 23 (6 Suppl. 16): 7–10

    PubMed  CAS  Google Scholar 

  94. Thomas P, Castelnau O, Paillotin D, et al. Phase II trial of paclitaxel and carboplatin in metastatic small-cell lung cancer: a Groupe Francais de Pneumo-Cancerologie study. J Clin Oncol 2001; 19(5): 1320–5

    PubMed  CAS  Google Scholar 

  95. Hainsworth JD, Gray JR, Stroup SL, et al. Paclitaxel, carboplatin, and extended-schedule etoposide in the treatment of small-cell lung cancer: comparison of sequential phase II trials using different dose-intensities. J Clin Oncol 1997; 15(12): 3464–70

    PubMed  CAS  Google Scholar 

  96. Mavroudis D, Papadakis E, Veslemes M, et al. A multicenter randomized clinical trial comparing paclitaxel-cisplatin-etopo-side versus cisplatin-etoposide as front-line treatment in patients with small cell lung cancer. Ann Oncol 2001; 12(4): 463–70

    Article  PubMed  CAS  Google Scholar 

  97. Niell HB, Herndon 2nd JE, Miller AA, et al. Randomized phase III intergroup trial of etoposide and cisplatin with or without paclitaxel and granulocyte colony-stimulating factor in patients with extensive-stage small-cell lung cancer: Cancer and Leukemia Group B Trial 9732. J Clin Oncol 2005; 23(16): 3752–9

    Article  PubMed  CAS  Google Scholar 

  98. Reck M, von Pawel J, Macha HN, et al. 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; 95(15): 1118–27

    Article  PubMed  CAS  Google Scholar 

  99. Reck M, von Pawel J, Macha HN, et al. Efficient palliation in patients with small-cell lung cancer by a combination of paclitaxel, etoposide and carboplatin: quality of life and 6-years’ follow-up results from a randomised phase III trial. Lung Cancer 2006; 53(1): 67–75

    Article  PubMed  Google Scholar 

  100. Smit EF, Groen HJ, Biesma B, et al. Phase III study comparing cyclophosphamide, doxorubicin, and etoposide (CDE) to carboplatin and paclitaxel (CP) in patients (pts) with extensive disease small cell lung cancer (ED SCLC) [abstract no. 7045]. 41st Annual Meeting of the American Society of Clinical Oncology; 2005 May 13–17; Orlando (FL). J Clin Oncol 2005; 23 (16S Suppl. 1): 7045

    Google Scholar 

  101. Baka S, Mullamitha S, Ashcroft L, et al. Randomized phase III study of carboplatin and paclitaxel versus vincristine, doxorubicin and cyclophosphamide chemotherapy in intermediate and poor prognosis small cell lung cancer: preliminary results [abstract no. 7059]. 42nd Annual Meeting of the American Society of Clinical Oncology; 2006 Jun 2–6; Atlanta (GA). J Clin Oncol 2006; 24 (18S Suppl. 1): 7059

    Google Scholar 

  102. Hanna N, Ansari R, Bhatia S, et al. Pemetrexed in patients with relapsed small cell lung cancer (SCLC): a phase II study of the Hoosier Oncology Group [abstract no. 7063]. 42nd Annual Meeting of the American Society of Clinical Oncology; 2006 Jun 2–6; Atlanta (GA). J Clin Oncol 2006, 24 (18S Suppl. 1): 7063

    Google Scholar 

  103. 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; 24(30): 4840–7

    Article  PubMed  CAS  Google Scholar 

  104. Ferraldeschi R, Thatcher N, Lorigan P. Pemetrexed in small cell lung cancer: an overview of the background and review of the ongoing GALES (Global Analysis of Pemetrexed in SCLC Extensice Stage) pivotal trial. Expert Rev Anticancer Ther 2007; 7(5): 635–40

    Article  PubMed  Google Scholar 

  105. 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; 24(34): 5448–53

    Article  PubMed  CAS  Google Scholar 

  106. Kato T, Nokihara H, Ohe Y, et al. Phase II trial of amrubicin in patients with previously treated small cell lung cancer [abstract no. 7061]. 42nd Annual Meeting of the American Society of Clinical Oncology; 2006 Jun 2–6; Atlanta (GA). J Clin Oncol 2006; 24 (18S Suppl. 1): 7061

    Google Scholar 

  107. Ohe Y, Negoro S, Matsui K, et al. Phase I-II study of amrubicin and cisplatin in previously untreated patients with extensive stage small cell lung cancer. Ann Oncol 2005; 16(3): 430–6

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  109. Davies A, Evans W, Mackay J, et al. Treatment of recurrent small cell lung cancer. Hematol Oncol Clin North Am 2004; 18(2): 387–416

    Article  PubMed  Google Scholar 

  110. James LE, Rudd R, Gower NH, et al. A phase III randomised comparison of gemcitabine/carboplatin (GC) with cisplatin/ etoposide (PE) in patients with poor prognosis small cell lung cancer (SCLC) [abstract no. 1170]. 38th Annual Meting of the American Society of Clinical Oncology; 2002 May 18–21; Orlando (FL)

  111. Board R, Thatcher N, Lorigan P. Novel therapies for the treatment of small-cell lung cancer: a time for cautious optimism. Drugs 2006; 66(15): 1919–31

    Article  PubMed  CAS  Google Scholar 

  112. 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(6): 1319–23

    PubMed  CAS  Google Scholar 

  113. Giaccone G, Debruyne C, Felip E, et al. Phase III study of adjuvant vaccination with Bec2/bacille Calmette-Guerin in responding patients with limited-disease small-cell lung cancer (European Organisation for Research and Treatment of Cancer 08971-08971B; Silva Study). J Clin Oncol 2005; 23(28): 6854–64

    Article  PubMed  CAS  Google Scholar 

  114. Pujol JL, Breton JL, Gervais R, et al. A prospective randomized phase III, double-blind, placebo-controlled study of thalido-mide in extended-disease (ED) SCLC patients after response to chemotherapy (CT): an intergroup study FNCLCC Cleo04-IFCT 00-01 [abstract no. 7057]. 42nd Annual Meeting of the American Society of Clinical Oncology; 2006 Jun 2–6; Atlanta (GA)

  115. Lee, S, Woll P, James L, et al. A Phase III randomized, double blind, placebo controlled trial od etoposide/carboplatin with or without thalidomide in advanced small cell lung cancer (SCLC) [abstract no. PRS-04]. 12th World Conference on Lung Cancer; 2007 Sep 2–7; Seoul

  116. 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(22): 4434–9

    Article  PubMed  CAS  Google Scholar 

  117. Fox W, Scadding J. Medical Research Council comparative trial of surgery and radiotherapy for primary treatment of small celled or oat celled carcinoma of the bronchus: ten-year follow-up. Lancet 1973; II(7820): 63–5

    Article  Google Scholar 

  118. Shields TW, Higgins Jr GA, Matthews MJ, et al. Surgical resection in the management of small cell carcinoma of the lung. J Thorac Cardiovasc Surg 1982; 84(4): 481–8

    PubMed  CAS  Google Scholar 

  119. Karrer K, Ulsberger E, for the ISC Lung Cancer Study Group. Surgery for cure followed by chemotherapy in small cell carcinoma of the lung. Acta Oncol 1995; 34: 899–906

    Article  PubMed  CAS  Google Scholar 

  120. Meyer JA, Gullo JJ, Ikins PM, et al. Adverse prognostic effect of N2 disease in treated small cell carcinoma of the lung. J Thorac Cardiovasc Surg 1984; 88(4): 495–501

    PubMed  CAS  Google Scholar 

  121. Meyer JA. Five-year survival in treated stage I and II small cell lung carcinoma of the lung. Ann Thorac Surg 1986; 42: 668–9

    Article  PubMed  CAS  Google Scholar 

  122. Shephard FA, Evans WK, Feld R, et al. Adjuvant chemotherapy following surgical resection for small-cell carcinoma of the lung. J Clin Oncol 1988; 8: 832–8

    Google Scholar 

  123. Davis S, Crino L, Tonato M, et al. A prospective analysis of chemotherapy following surgical resection of clinical stage I-II small-cell lung cancer. Am J Clin Oncol 1993; 16: 93–5

    Article  PubMed  CAS  Google Scholar 

  124. Hara N, Ohta M, Ichinose Y, et al. Influence of surgical resection before and after chemotherapy on survival in small cell lung cancer. J Surg Oncol 1991; 47: 53–61

    Article  PubMed  CAS  Google Scholar 

  125. Macchiarini P, Hardin M, Basolo F, et al. Surgery plus adjuvant chemotherapy for T1-3NOMO small-cell lung cancer. Am J Clin Oncol 1991; 14: 218–24

    Article  PubMed  CAS  Google Scholar 

  126. Brock MV, Hooker CM, Syphard JE, et al. Surgical resection of limited disease small cell lung cancer in the new era of platinum chemotherapy: its time has come. J Thorac Cardiovasc Surg 2005; 129(1): 64–72

    Article  PubMed  Google Scholar 

  127. Shepard FA, Ginsberg RJ, Patterson GA, et al. A prospective study of adjuvant surgical resection after chemotherapy for limited small cell lung cancer. Thorax 1989; 97: 177–86

    Google Scholar 

  128. Baker RR, Ettinger DS, Ruckdeschel JC, et al. The role of surgery in the management of selected patients with small cell carcinoma of the lung. J Clin Oncol 1987; 5: 697–702

    PubMed  CAS  Google Scholar 

  129. Johnson DH, Einhorn LH, Mandelbaum I, et al. Postchemotherapy resection of residual tumor in limited stage small cell lung cancer. Chest 1987; 92: 241–6

    Article  PubMed  CAS  Google Scholar 

  130. Prager RL, Foster JM, Hainsworth JD, et al. The feasibility of adjuvant surgery in limited-stage small cell carcinoma: a prospective evaluation. Ann Thorac Surg 1984; 38: 622–6

    Article  PubMed  CAS  Google Scholar 

  131. Lad T, Piantadosi S, Thomas P, et al. A prospective randomized trial to determine the benefit of surgical resection of residual disease following response of small cell lung cancer to combination chemotherapy. Chest 1994; 106: 320–323S

    Article  Google Scholar 

  132. Perez CA, Einhorn R, Oldham RK, et al. Randomised trial of radiotherapy to the thorax in limited small cell carcinoma of the lung treated with multiagent chemotherapy and elective brain irradiation: a preliminary report. J Clin Oncol 1984; 2(11): 1200–8

    PubMed  CAS  Google Scholar 

  133. Perry MC, Eaton WL, Propert KJ, et al. Chemotherapy with or without radiation therapy in limited stage small cell lung cancer. N Engl J Med 1987; 316(15): 912–8

    Article  PubMed  CAS  Google Scholar 

  134. Bunn Jr PA, Lichter AS, Makuch RW, et al. Chemotherapy alone or chemotherapy with chest radiation therapy in limited-stage small-cell lung cancer. Ann Intern Med 1987; 106(5): 655–62

    PubMed  Google Scholar 

  135. Pignon JP, Arriagada R, Idhe DC, et al. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med 1992; 327(23): 1618–22

    Article  PubMed  CAS  Google Scholar 

  136. Warde P, Payne D. Does thoracic irradiation improve survival and local control in limited-stage small-cell lung cancer? J Clin Oncol 1992; 10(6): 890–5

    PubMed  CAS  Google Scholar 

  137. Choi NC, Carey RW. Importance of radiation dose in achieving improved loco-regional tumour control in limited stage small-call lung carcinoma: an update. Int J Radiat Oncol Biol Phys 1989; 17: 307–10

    Article  PubMed  CAS  Google Scholar 

  138. Roof K, Fidias P, Lynch T. Radiation dose escalation in limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys 2003; 57: 701–8

    Article  PubMed  Google Scholar 

  139. Miller K, Marks L, Sibley G, et al. Routine use of approximately 60 Gy once-daily thoracic irradiation for patients with limited-dose small-cell lung cancer. Int J Radiat Oncol Biol Phys 2003; 56: 355–9

    Article  PubMed  Google Scholar 

  140. Carney DN, Mitchell JB, Kinsella TJ. In vitro radiation and chemotherapy sensitivity of estabilished cell lines of human small cell lung cancer and its large cell morphological variants. Cancer Res 1983; 43(6): 2806–11

    PubMed  CAS  Google Scholar 

  141. Turrisi 3rd AT, Kim K, Blum R, et al. Twice daily compared to once-daily thoracic radiotherapy in limited-stage small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 1999; 340(4): 265–71

    Article  PubMed  CAS  Google Scholar 

  142. Bonner JA, Sloan JA, Shanahan TG, et al. 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): 2681–91

    PubMed  CAS  Google Scholar 

  143. 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(14): 3054–60

    Article  PubMed  CAS  Google Scholar 

  144. Jeremic B, Shibamoto Y, Acimovic L, et al. Initial versus delayed accelerated hyperfractionated radiation therapy and concurrent chemotherapy in limited small-cell lung cancer: a randomized study. J Clin Oncol 1997; 15(3): 893–900

    PubMed  CAS  Google Scholar 

  145. 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(2): 336–44

    CAS  Google Scholar 

  146. Work E, Nielsen OS, Bentzen SM, et al. Randomized study of initial versus late chest irradiation combined with chemotherapy in limited-stage small-cell lung cancer. Aarhus Lung Cancer Group. J Clin Oncol 1997; 15(9): 3030–7

    CAS  Google Scholar 

  147. Skarlos DV, Samantas E, Briassoulis E, et al. Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol 2001; 12(9): 1231–8

    Article  PubMed  CAS  Google Scholar 

  148. Lebeau B, Urban T, Brechot JM, et al. A randomized clinical trial comparing concurrent and alternating thoracic irradiation for patients with limited small cell lung carcinoma: “Petites Cellules” Group. Cancer 1999; 86(8): 1480–7

    Article  PubMed  CAS  Google Scholar 

  149. Perry MC, Herndon 3rd JE, Eaton WL. Thoracic radiation therapy added to chemotherapy for small-cell lung cancer: an update of Cancer and Leukemia Group B Study 8083. J Clin Oncol 1998; 16(7): 2466–7

    PubMed  CAS  Google Scholar 

  150. Gregor A, Drings P, Burghouts J, et al. Randomized trial of alternating versus sequential radiotherapy/chemotherapy in limited-disease patients with small-cell lung cancer: a European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group Study. J Clin Oncol 1997; 15(8): 2840–9

    PubMed  CAS  Google Scholar 

  151. Spiro SG, James LE, Rudd RM, et al. Early compared with late radiotherapy in combined modality treatment for limited disease small-cell lung cancer: a London Lung Cancer Group multicenter randomized clinical trial and meta analysis. J Clin Oncol 2006; 24(24): 3823–30

    Article  PubMed  CAS  Google Scholar 

  152. Fried DB, Morris DE, Poole C, et al. Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited stage small-cell lung cancer. J Clin Oncol 2004; 22(23): 4837–45

    Article  PubMed  Google Scholar 

  153. de Ruysscher D, Pijls-Johannesma M, Vansteenkiste J, et al. Systematic review and meta-analysis of randomised, controlled trials of the timing of chest radiotherapy in patients with limited-stage, small-cell lung cancer. Ann Oncol 2006; 17(4): 543–52

    Article  PubMed  Google Scholar 

  154. de Ruysscher D, Pijls-Johannesma M, Bentzen SM, 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; 24(7): 1057–63

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  156. Komaki R, Meyers CA, Shin DM, et al. Evaluation of cognitive function in patients with limited small cell lung cancer prior to and shortly following prophylactic cranial irradiation. Int J Radiat Oncol Biol Phys 1995; 33(1): 179–82

    Article  PubMed  CAS  Google Scholar 

  157. Gregor A, Cull A, Stephens RJ, et al. Prophylactic cranial irradiation is indicated following complete response to induction therapy in small cell lung cancer: results of a multicentre randomised trial. United Kingdom Coordinating Committee for Cancer Research (UKCCCR) and the European Organization for Research and Treatment of Cancer (EORTC). Eur J Cancer 1997; 33(11): 1752–8

    PubMed  CAS  Google Scholar 

  158. Faivre-Finn C, Lorigan P, West C, et al. Dilemas in the radiation treatment for SCLC. Clin Lung Cancer 2005; 7(1): 23–9

    Article  PubMed  Google Scholar 

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

    Roberta Ferraldeschi, Sofia Baka, Babita Jyoti, Corinne Faivre-Finn, Nick Thatcher &  Paul Lorigan

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  1. Roberta Ferraldeschi
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Ferraldeschi, R., Baka, S., Jyoti, B. et al. Modern Management of Small-Cell Lung Cancer. Drugs 67, 2135–2152 (2007). https://doi.org/10.2165/00003495-200767150-00003

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