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Original article

Vol. 141 No. 2122 (2011)

Sequential or concomitant chemotherapy in limited stage small-cell lung cancer

  • K Khanfir
  • M Elhfidh
  • S Anchisi
  • S Bieri
Cite this as:
Swiss Med Wkly. 2011;141:w13205


PURPOSE: Chemotherapy (CT) combined with radiation therapy (RT) is the standard treatment for limited disease small-cell lung cancer (LDSCLC). Many questions including RT dose, fractionation, and sequence of RT/CT administration remain controversial. In this paper, we retrospectively assessed the outcome of patients with LDSCLC treated with radiation of at least 50 Gy.

METHODS AND MATERIALS: From December 1997 to January 2006, 69 consecutive patients with LDSCLC were treated at our institutions. Treatment consisted of at least 4 cycles of CT, and 3D conformal thoracic RT. The median age was 61 years (range, 37–78 years). Sequential or concomitant CT/RT was given in 47 (68%) and 22 (32%) of the patients, respectively. The median RT dose was 60 Gy. Prophylactic cranial irradiation (PCI) was administered in 47 (68%) patients.

RESULTS: With a median follow-up of 36 months (range, 6–107), 16 patients were alive without disease. The median overall survival time was 24 months, with a 3-year survival rate of 29%. The 3-year disease-free survival (DFS) and loco-regional control (LRC) rates were 23% and 60%, respectively. A better DFS was significantly associated with performance status (PS) 0 (p = 0.004), complete response to treatment (p= 0.03), and PCI group (p = 0.03). A trend towards improved overall survival (OS) was observed for patients who underwent PCI (p = 0.07). Patients treated with sequential CT/RT had a better outcome than those treated with concomitant treatment (3-year DFS rate 27% vs. 13%; p = 0.04). However, PCI was delivered more frequently for the sequential group. No significant dose-response relationship was found in terms of LRC. The multivariate analysis showed that complete response to treatment was the only significant factor for OS.

CONCLUSION: Complete response to treatment was the most important factor for OS. A better DFS was significantly associated with the PCI group. We did not find a significant difference in outcome between patients receiving doses of 60 Gy or more and patients receiving 60 Gy or less.


  1. Perry MC, Eaton WL, Propert KJ, et al. Chemotherapy alone or chemotherapy with chest radiation therapy in limited small-cell carcinoma of the lung. N Engl J Med. 1987;316:912–8.
  2. Pignon JP, Arriagada R, Ihde DC, et al. Meta-analysis of thoracic radiotherapy for small-cell lung cancer: unanswered questions. Squamous cell carcinoma of the anal margin. N Engl J Med. 1992;327:1618–24.
  3. Warde P, Payne D. Does thoracic irradiation improve survival and local control in limited small-cell carcinoma of the lung? A meta-analysis. J Clin Oncol. 1992;10:890–5.
  4. Auperin A, Arriagada R, Pignon JP, Le Péchoux C, Gregor A, Stephens R, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med. 1999;341:476–84.
  5. Turrisi AT, Kyungmann K, Blum R,Sause WT, Livingstone RB, Komaki 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;340:265–71.
  6. Evans WK, Shepherd FA, Feld, et al. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985;3:1471–7.
  7. American Joint Committee on Cancer: AJCC cancer staging manual. New York: Springer; 2002.
  8. International Union Against Cancer: TNM classification of malignant tumours. New York: Wiley-Liss, Inc.; 1998.p.17–47.
  9. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.
  10. Peto P, Pike MC, Armitage P, et al. Design and analysis of randomised clinical trials requiring prolonged observation of each patient: Part II. Br J Cancer. 1977;35:1–39.
  11. Beck-Bornholdt HP, Dubben HH. Potential pitfalls in the use of p-values and in interpretation of significance levels. Radiother Oncol. 1994;33:171–6.
  12. Trotti A, Colevas AD, Setser A, et al. CTCAE v.3: Development of a comprehensive Grading System for the adverse events of cancer treatment. Semin Radiat Oncol. 2003;13:176–81.
  13. Fried DB, Morris DE, Poole C, et al. Systematic review evaluating the timing of thoracic radiotherapy in combined-modality therapy for limited-stage small-cell lung cancer. J Clin Oncol. 2004;23:4785–93.
  14. 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. J Clin Oncol. 1993;11:336–44.
  15. De Ruysscher D, Pijls-Johannesma M, Van-steenkiste 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;543–52.
  16. Jeremic B, Shibamato 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;15:893–900.
  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;20:3054–60.
  18. 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;15:2840–9.
  19. Spiro SG, James LE, Rudd RM, et al. Early compared with late radiotherapy in combined-modality treatment for limited-disease small-cell lung: A London Lung Cancer Group multicenter randomized clinical trial and meta-analysis. J Clin Oncol. 2006;24:3823–30.
  20. Perry MC, Herndon JE III, Eaton WL, et al. Thoracic radiation therapy added to chemotherapy for small cell lung cancer: An update of Cancer and Leukemia Group B study 8083. J Clin Oncol. 1998,16:2466–7.
  21. Skarlos DV, Samantas E, Briassoulis E, et al. Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrent with chemotherapy in limited-disease small-cell lung cancer: A randomized phase II study of the Hellenic Cooperative oncology group(HeCOG). Annal Oncol. 2001;12:1231–8.
  22. Albain KS, Crowly JJ, LeBlanc M, et al. Determinants of improved outcome in small-cell lung cancer: An analysis of the 2,850-patient Southwest Oncology Group data base. J Clin Oncol. 1990;8:1563–74.
  23. 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 year’s follow-up. J Clin Oncol. 2002;20:4665–72.
  24. Wolf M, Havemann K, Holle R, et al. Cisplatin/etoposide combination versus ifosfamide-etoposide combination in small-cell lung cancer: A multicenter German randomized trial. J Clin Oncol. 1987;5:1880–9.
  25. a 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;13:2594–9.
  26. Thatcher N. Ifosfamide, carboplatin, etoposide (ICE) regimen in small cell lung cancer. Lung Cancer. 1993;9:51–4.
  27. Fetscher S, Brugger W, Engelhardt R, et al. Dose-intense therapy with etoposide, ifosfamide, cisplatin, and epirubicin (VIP-E) in 100 consecutive patients with limited-and extensive-disease small-cell lung cancer. Ann Oncol. 1997;8:49–56.
  28. Leyvraz S, Pampallona S, Martinelli G, et al. A threefold dose intensity treatment with ifosfamide, carboplatin, and etoposide for patients with small cell lung cancer: A randomized trial. JNCI. 2008;100:533–41.
  29. Glisson BS, Kurie JM, Perez-Soler R, et al. Cisplatin, etoposide and paclitaxel in the treatment of patients with extensive small cell lung carcinoma. J Clin Oncol. 1999;17:2309–13.
  30. Mavroudis D, Papadakis E, Georgoulias V, et al. A multicenter randomized clinical trial comparing paclitaxel-cisplatin-etoposide versus cisplatin-etoposide as first-line treatment in patients with small-cell lung cancer. Ann Oncol. 2001;12:463–70.
  31. Baas P, Belderbos JSA, Senan S, et al. Concurrent chemotherapy (carboplatin, placlitaxel, etoposide) and involved-field radiotherapy in limited stage small cell lung cancer: a Dutch multicenter phase II study. BJC. 2006;94:625–30.
  32. Choi NC, Carey RW. Importance of radiation dose in achieving improved loco-regional tumor control in limited stage small-cell lung carcinoma. Int J Radiat Oncol Biol Phys. 1989;17:307–10.
  33. Roof KS, Fidias P, Lynch TJ, et al. Radiation dose escalation in limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2003;57:701–8.
  34. Coy P, Hodson I, Payne DG, et al. The effect of dose of thoracic irradiation on recurrence in patients with limited stage small cell lung cancer. Initial results of a Canadian multicenter randomized trial. Int J Radiat Oncol Biol Phys. 1988;14:219–26.
  35. 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;17:2681–91.
  36. Choi N, Herndon J, Rosenman J, et al. Phase I study to determine the maximum-tolerated dose of radiation in standard daily and hyperfractionated-accelerated twice daily radiation schedules with concurrent chemotherapy for limited-stage small-cell lung cancer. J Clin Oncol. 1998;16:3528–36.
  37. Bogart JA, Herndon JE, Lyss A, et al. 70 Gy thoracic radiotherapy is feasible concurrent with chemotherapy for limited-stage small-cell lung cancer: Analysis of Cancer and Leukaemia Group B study 39808. Int J Radiat Oncol Biol Phys. 2004;59:460–8.
  38. Slotman B, Faivre-Finn C, Kramer G, et al. Prophylactic cranial irradiation in extensive small cell lung cancer. N Engl J Med. 2007;357:664–70.