Summary
Following mediastinoscopy, a prognostically orientated multimodality approach was chosen in selected small-cell lung cancer (SCLC) patients with hyperfractionated accelerated chemoradiotherapy (Hf-RTx) and definitive surgery (S). Stage IB/IIA patients had four cycles of cisplatin/etoposide (PE) and surgery. Stage IIB/IIIA patients had three cycles PE followed by one cycle concurrent chemoradiation including Hf-RTx and surgery. Most stage IIIB patients were not planned for surgery and had CTx followed by sequential RTx or one cycle concurrent CTx/RTx. Of 46 consecutive patients (stage IB six, IIA two, IIB/IIIA 22, IIIB 16) 43 (94%) showed an objective response. Twenty-three of patients (72%) planned for inclusion of S were completely resected (R0) (IB 6/6, IIA 2/2, IIB/IIIA 13/22, IIIB 2/2). Overall toxicity was acceptable – one patient died of septicaemia, no perioperative deaths occurred. Median follow-up of patients alive (n = 21) is 52 months (30+ – 75+). Median survival and 5-year survival rate of all patients are 36 months and 46%, in R0 patients 68 months and 63% (R0-IIB/IIIA/IIIB: not yet reached and 67%). This multimodality treatment including surgery proved highly effective with 100% local control and remarkable long-term survival after complete resection, even in locally advanced SCLC stages IIB/IIIA patients.
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References
Arriagada, R, Kramar, A, Le Chevalier, T & De Cremoux, H (1992). Competing events determining relapse-free survival in limited small-cell lung carcinoma. J Clin Oncol 10: 447–451.
Arriagada, R, Le Chevalier, T, Borie, F, Rivière, A, Chomy, P, Monnet, I, Tardivon, A, Viader, F, Tarayre, M & Benhamou, S (1995). Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. J Natl Cancer Inst 87: 183–190.
Arriagada, R, Auperin, A, Pignon, JP, Gregor, A, Stephens, R, Kristjansen, PEG, Johnson, B, Ueoka, H, Wagner, H & Whitacre, M (1998). Prophylactic cranial irradiation overview in patients with small-cell lung cancer in complete remission. Proc Am Soc Clin Oncol 17: 457 (abstr 1758)
Choi, NC, Carey, RW, Daly, W, Mathisen, D, Wain, J, Wright, C, Lynch, T, Grossbard, M & Grillo, H (1997). Potential impact on survival of improved tumor downstaging and resection rate by preoperative twice-daily radiation and concurrent chemotherapy in stage IIIA non-small-cell lung cancer. J Clin Oncol 15: 712–722.
Davis, S, Crino, L, Tonato, M, Darwish, S, Pelicci, PG & Grignani, F (1993). A prospective analysis of chemotherapy following surgical resection of clinical stage I–II small cell lung cancer. Am J Clin Oncol 16: 93–95.
Eberhardt, W, Wilke, H, Stamatis, G, Stuschke, M, Harstrick, A, Menker, H, Krause, B, Müller, MR, Stahl, M, Flasshove, M, Budach, V, Greschuchna, D, Konietzko, N, Sack, H & Seeber, S (1998). Preoperative chemotherapy followed by concurrent chemoradiation therapy based upon hyperfractionated accelerated radiotherapy and definitive surgery in locally advanced non-small-cell lung cancer: mature results of a phase II trial. J Clin Oncol 16: 622–634.
Elias, AD, Ayash, L, Frei, III E, Skarin, AT, Hunt, M, Wheeler, C, Schwartz, G, Mazanet, R, Tepler, I, Eder, JP, McCauley, M, Herman, T, Schnipper, L & Antman, KH (1993). Intensive combined modality therapy for limited-stage small-cell lung cancer. J Natl Cancer Inst 85: 559–566.
Elias, AD (1997a). Small cell lung cancer: state-of-the-art therapy in 1996. Chest 112: 251S–258S.
Elias, AD (1997b). Dose-intensive therapy in lung cancer. Cancer Chemother Pharmacol 40: S64–S69.
Fetscher, S, Brugger, W, Engelhardt, R, Kanz, L, Hasse, J, Frommhold, H, Wenger, M, Lange, W & Mertelsmann, R (1997). 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 8: 49–56.
Gray, JR, Sobczak, ML, Hahn, SM, Sullivan, FJ, Johnson, BE & Bridges, JD (1995). Analysis of local control in 150 limited stage small-cell-lung cancer patients treated with combined thoracic irradiation and multiagent chemotherapy. Proc Am Soc Clin Oncol 14: 349 (abstr 1056)
Green, MR, Cox, JD, Ardizzoni, A, Arriagada, R, Bureau, G, Darwish, S, Deneffe, G, Fukuoka, M, Joseph, D & Komaki, R (1994). Endpoints for multimodal clinical trials in stage III non-small cell lung cancer (NSCLC): a consensus report. Lung Cancer 11, Suppl 3: S11–S13.
Gridelli, C, D’Aprile, M, Curcio, C, Brancaccio, L, Palmeri, S, Comella, G, Veltri, E, Ferrante, G, Gentile, M & Rossi, A (1994). Carboplatin plus epirubicin plus VP-16, concurrent ‘split course’ radiotherapy, and adjuvant surgery for limited small-cell lung cancer. Lung Cancer 11: 83–91.
Ihde, DC, Pass, HI & Glatstein, EJ (1997). Small cell lung cancer. In: Cancer: Principles and Practice of Oncology, 5th edn, DeVita VT Jr Hellman, S Rosenberg SA (eds), pp. 911–949.Lippincott: Philadelphia 911–949.
Johnson, DH, Kim, K, Sause, W, Komaki, R, Wagner, H, Aisner, S, Livingston, R, Blum, R & Turrisi, AT (1996). Cisplatin and etoposide plus thoracic radiotherapy administered once or twice daily in limited stage small cell lung cancer: Final report of Intergroup Trial 0096. Proc Am Soc Clin Oncol 15: 374 (abstr 1113)
Kaplan, EL & Meier, P (1958). Nonparametric estimation from incomplete observations. J Am Statist Assoc 53: 457–481.
Lad, T, Piantadosi, S, Thomas, P, Payne, D, Ruckdeschel, J & Giaccone, G (1994). 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 106: 320S–323S.
McCracken, JD, Janaki, LM, Crowley, JJ, Taylor, SA, Shankir Giri, PG, Weiss, GB, Gordon, W, Baker, LH, Mansouri, A & Kuebler, JP (1990). Concurrent chemotherapy/radiotherapy for limited small-cell lung carcinoma: a Southwest Oncology Group study. J Clin Oncol 8: 892–898.
Macchiarini, P, Mussi, A, Basolo, F, Bruno, J & Angeletti, CA (1989). Optimal treatment for T1-3N0M0 small cell lung cancer: surgery plus adjuvant chemotherapy. Anticancer Res 9: 1623–1625.
Mantel, N (1966). Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50: 163–170.
Meyer, JA, Gullo, JJ, Ikins, PM, Comis, RL, Burke, WA, Di Fino, SM & Parker, FB Jr (1984). Adverse prognostic effect of N2 disease in treated small-cell carcinoma of the lung. J Thorac Cardiovasc Surg 88: 495–501.
Miller, AB, Hoogstraten, B, Staquet, M & Winkler, A (1981). Reporting results of cancer treatment. Cancer 47: 207–214.
Mountain, CF (1997). Revisions in the international system staging lung cancer. Chest 111: 1710–1717.
Müller, LC, Salzer, GM, Huber, H, Prior, C, Ebner, I, Frommhold, H & Präuer, HW (1992). Multimodal therapy of small cell lung cancer in TNM stages I through IIIa. Ann Thorac Surg 54: 493–497.
Parker, SL, Tong, T, Bolden, S & Wingo, PA (1997). Cancer statistics, 1997. CA Cancer J Clin 47: 5–27.
Pignon, JP, Arriagada, R, Ihde, DC, Johnson, DH, Perry, MC, Souhami, RL, Brodin, O, Joss, RA, Kies, MS, Lebeau, B, Onoshi, T, Osterlind, K, Tattersall, MHN & Wagner, H (1992). A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med 327: 1618–1624.
Shepherd, FA, Evans, WK, Feld, R, Young, V, Patterson, GA, Ginsberg, R & Johansen, E (1988). Adjuvant chemotherapy following surgical resection for small-cell carcinoma of the lung. J Clin Oncol 6: 832–838.
Shepherd, FA, Ginsberg, RJ, Patterson, GA, Evans, WK & Feld, R (1989). A prospective study of adjuvant surgical resection after chemotherapy for limited small cell lung cancer. A University of Toronto Lung Oncology Group study. J Thorac Cardiovasc Surg 97: 177–186.
Shepherd, FA, Ginsberg, RJ, Haddad, R, Feld, R, Sagman, U, Evans, WK, De Boer, G & Maki, E (1993). Importance of clinical staging in limited small-cell lung cancer: a valuable system to separate prognostic subgroups. J Clin Oncol 11: 1592–1597.
Shepherd, F (1996). Surgical management of small-cell lung cancer. InLung Cancer: Principles and Practice, Pass HI, Mitchell JB, Johnson DH, Turrisi AT Lippincott-Raven: Philadelphia 889–913.
Takada, M, Fukuoka, M, Furuse, K, Ariyoshi, Y, Ikegami, H, Kurita, Y, Nishiwaki, Y, Nishiwaki, H, Watanabe, K, Noda, K & Saijo, N (1996). Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small cell lung cancer: Preliminary results of the Japan Clinical Oncology Group. Proc Am Soc Clin Oncol 15: 372 (abstract 1103)
Turrisi, AT, Glover, DJ, Mason, B & Tester, W (1992). Long term results of platinum etoposide + twice-daily thoracic radiotherapy for limited small-cell lung cancer: results on 32 patients with 48 months minimum F/U. Proc Am Soc Clin Oncol 11: 292 (abstract 975)
Turrisi, AT, Kim, K, Blum, R, Sause, WT, Livingston, RB, Komaki, R, Wagner, H, Aisner, S & Johnson, DH ). Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 340: 265–271.
Ulsperger, E, Karrer, K & Denck, H (1991). Multimodality treatment for small cell lung cancer. Preliminary results of a prospective, multicenter trial. The ISC-Lung Cancer Study Group. Eur J Cardiothorac Surg 5: 306–310.
Wilke, H, Achterrath, W, Schmoll, HJ, Gunzer, U, Preusser, P & Lenaz, L (1988). Etoposide and split-dose cisplatin in small cell lung cancer. Am J Clin Oncol 11: 572–578.
Zatopek, NK, Holoye, PY, Ellerbroek, NA, Hong, WK, Roth, JA, Ryan, MB, Komaki, R, Pang, AC & Glisson, BS (1991). Resectability of small cell lung cancer following induction chemotherapy in patients with limited disease (stage II–IIIb). Am J Clin Oncol 14: 427–432.
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Eberhardt, W., Stamatis, G., Stuschke, M. et al. Prognostically orientated multimodality treatment including surgery for selected patients of small-cell lung cancer patients stages IB to IIIB: Long-term results of a phase II trial. Br J Cancer 81, 1206–1212 (1999). https://doi.org/10.1038/sj.bjc.6690830
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DOI: https://doi.org/10.1038/sj.bjc.6690830
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