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. 1999 Dec;81(7):1206–1212. doi: 10.1038/sj.bjc.6690830

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

W Eberhardt 1, G Stamatis 3, M Stuschke 2, H Wilke 1, M R Müller 1, S Kolks 1, M Flasshove 1, J Schütte 1, M Stahl 1, L Schlenger 1, V Budach 2, D Greschuchna 3, G Stüben 2, H Teschler 3, H Sack 2, S Seeber 1
PMCID: PMC2374330  PMID: 10584883

Abstract

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. © 1999 Cancer Research Campaign

Keywords: small-cell lung cancer, combined modality, surgery, neoadjuvant

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Selected References

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  1. Arriagada R., Kramar A., Le Chevalier T., De Cremoux H. Competing events determining relapse-free survival in limited small-cell lung carcinoma. The French Cancer Centers' Lung Group. J Clin Oncol. 1992 Mar;10(3):447–451. doi: 10.1200/JCO.1992.10.3.447. [DOI] [PubMed] [Google Scholar]
  2. Arriagada R., Le Chevalier T., Borie F., Rivière A., Chomy P., Monnet I., Tardivon A., Viader F., Tarayre M., Benhamou S. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. J Natl Cancer Inst. 1995 Feb 1;87(3):183–190. doi: 10.1093/jnci/87.3.183. [DOI] [PubMed] [Google Scholar]
  3. Choi N. C., Carey R. W., Daly W., Mathisen D., Wain J., Wright C., Lynch T., Grossbard M., Grillo H. 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. 1997 Feb;15(2):712–722. doi: 10.1200/JCO.1997.15.2.712. [DOI] [PubMed] [Google Scholar]
  4. Davis S., Crino L., Tonato M., Darwish S., Pelicci P. G., Grignani F. A prospective analysis of chemotherapy following surgical resection of clinical stage I-II small-cell lung cancer. Am J Clin Oncol. 1993 Apr;16(2):93–95. doi: 10.1097/00000421-199304000-00001. [DOI] [PubMed] [Google Scholar]
  5. Eberhardt W., Wilke H., Stamatis G., Stuschke M., Harstrick A., Menker H., Krause B., Müeller M. R., Stahl M., Flasshove M. Preoperative chemotherapy followed by concurrent chemoradiation therapy based on hyperfractionated accelerated radiotherapy and definitive surgery in locally advanced non-small-cell lung cancer: mature results of a phase II trial. J Clin Oncol. 1998 Feb;16(2):622–634. doi: 10.1200/JCO.1998.16.2.622. [DOI] [PubMed] [Google Scholar]
  6. Elias A. D., Ayash L., Frei E., 3rd, Skarin A. T., Hunt M., Wheeler C., Schwartz G., Mazanet R., Tepler I., Eder J. P. Intensive combined modality therapy for limited-stage small-cell lung cancer. J Natl Cancer Inst. 1993 Apr 7;85(7):559–566. doi: 10.1093/jnci/85.7.559. [DOI] [PubMed] [Google Scholar]
  7. Elias A. D. Small cell lung cancer: state-of-the-art therapy in 1996. Chest. 1997 Oct;112(4 Suppl):251S–258S. doi: 10.1378/chest.112.4_supplement.251s. [DOI] [PubMed] [Google Scholar]
  8. Elias A. Dose-intensive therapy in lung cancer. Cancer Chemother Pharmacol. 1997;40 (Suppl):S64–S69. doi: 10.1007/s002800051064. [DOI] [PubMed] [Google Scholar]
  9. Fetscher S., Brugger W., Engelhardt R., Kanz L., Hasse J., Frommhold H., Wenger M., Lange W., Mertelsmann R. 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 Jan;8(1):49–56. doi: 10.1023/a:1008232329498. [DOI] [PubMed] [Google Scholar]
  10. Green M. R., Cox J. D., Ardizzoni A., Arriagada R., Bureau G., Darwish S., Deneffe G., Fukuoka M., Joseph D., Komaki R. Endpoints for multimodal clinical trials in stage III non-small cell lung cancer (NSCLC): a consensus report. Lung Cancer. 1994 Nov;11 (Suppl 3):S11–S13. doi: 10.1016/0169-5002(94)91859-7. [DOI] [PubMed] [Google Scholar]
  11. Gridelli C., D'Aprile M., Curcio C., Brancaccio L., Palmeri S., Comella G., Veltri E., Ferrante G., Gentile M., Rossi A. Carboplatin plus epirubicin plus VP-16, concurrent 'split course' radiotherapy and adjuvant surgery for limited small cell lung cancer. Gruppo Oncologico Centro-Sud-Isole (GOCSI). Lung Cancer. 1994 Jul;11(1-2):83–91. doi: 10.1016/0169-5002(94)90285-2. [DOI] [PubMed] [Google Scholar]
  12. Lad T., Piantadosi S., Thomas P., Payne D., Ruckdeschel J., Giaccone G. 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 Dec;106(6 Suppl):320S–323S. doi: 10.1378/chest.106.6_supplement.320s. [DOI] [PubMed] [Google Scholar]
  13. Macchiarini P., Mussi A., Basolo F., Bruno J., Angeletti C. A. Optimal treatment for T1-3NOMO small cell lung cancer: surgery plus adjuvant chemotherapy. Anticancer Res. 1989 Nov-Dec;9(6):1623–1625. [PubMed] [Google Scholar]
  14. Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep. 1966 Mar;50(3):163–170. [PubMed] [Google Scholar]
  15. McCracken J. D., Janaki L. M., Crowley J. J., Taylor S. A., Giri P. G., Weiss G. B., Gordon W., Jr, Baker L. H., Mansouri A., Kuebler J. P. Concurrent chemotherapy/radiotherapy for limited small-cell lung carcinoma: a Southwest Oncology Group Study. J Clin Oncol. 1990 May;8(5):892–898. doi: 10.1200/JCO.1990.8.5.892. [DOI] [PubMed] [Google Scholar]
  16. Meyer J. A., Gullo J. J., Ikins P. M., Comis R. L., Burke W. A., DiFino S. M., Parker F. B., Jr Adverse prognostic effect of N2 disease in treated small cell carcinoma of the lung. J Thorac Cardiovasc Surg. 1984 Oct;88(4):495–501. [PubMed] [Google Scholar]
  17. Miller A. B., Hoogstraten B., Staquet M., Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207–214. doi: 10.1002/1097-0142(19810101)47:1<207::aid-cncr2820470134>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  18. Mountain C. F. Revisions in the International System for Staging Lung Cancer. Chest. 1997 Jun;111(6):1710–1717. doi: 10.1378/chest.111.6.1710. [DOI] [PubMed] [Google Scholar]
  19. Müller L. C., Salzer G. M., Huber H., Prior C., Ebner I., Frommhold H., Präuer H. W. Multimodal therapy of small cell lung cancer in TNM stages I through IIIa. Ann Thorac Surg. 1992 Sep;54(3):493–497. doi: 10.1016/0003-4975(92)90441-6. [DOI] [PubMed] [Google Scholar]
  20. Parker S. L., Tong T., Bolden S., Wingo P. A. Cancer statistics, 1997. CA Cancer J Clin. 1997 Jan-Feb;47(1):5–27. doi: 10.3322/canjclin.47.1.5. [DOI] [PubMed] [Google Scholar]
  21. Pignon J. P., Arriagada R., Ihde D. C., Johnson D. H., Perry M. C., Souhami R. L., Brodin O., Joss R. A., Kies M. S., Lebeau B. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med. 1992 Dec 3;327(23):1618–1624. doi: 10.1056/NEJM199212033272302. [DOI] [PubMed] [Google Scholar]
  22. Shepherd F. A., Evans W. K., Feld R., Young V., Patterson G. A., Ginsberg R., Johansen E. Adjuvant chemotherapy following surgical resection for small-cell carcinoma of the lung. J Clin Oncol. 1988 May;6(5):832–838. doi: 10.1200/JCO.1988.6.5.832. [DOI] [PubMed] [Google Scholar]
  23. Shepherd F. A., Ginsberg R. J., Haddad R., Feld R., Sagman U., Evans W. K., DeBoer G., Maki E. Importance of clinical staging in limited small-cell lung cancer: a valuable system to separate prognostic subgroups. The University of Toronto Lung Oncology Group. J Clin Oncol. 1993 Aug;11(8):1592–1597. doi: 10.1200/JCO.1993.11.8.1592. [DOI] [PubMed] [Google Scholar]
  24. Shepherd F. A., Ginsberg R. J., Patterson G. A., Evans W. K., Feld R. 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. 1989 Feb;97(2):177–186. [PubMed] [Google Scholar]
  25. Ulsperger E., Karrer K., Denck H. Multimodality treatment for small cell bronchial carcinoma. Preliminary results of a prospective, multicenter trial. The ISC-Lung Cancer Study Group. Eur J Cardiothorac Surg. 1991;5(6):306–310. doi: 10.1016/1010-7940(91)90040-q. [DOI] [PubMed] [Google Scholar]
  26. Wilke H., Achterrath W., Schmoll H. J., Gunzer U., Preusser P., Lenaz L. Etoposide and split-dose cisplatin in small-cell lung cancer. Am J Clin Oncol. 1988 Oct;11(5):572–578. doi: 10.1097/00000421-198810000-00013. [DOI] [PubMed] [Google Scholar]
  27. Zatopek N. K., Holoye P. Y., Ellerbroek N. A., Hong W. K., Roth J. A., Ryan M. B., Komaki R., Pang A. C., Glisson B. S. Resectability of small-cell lung cancer following induction chemotherapy in patients with limited disease (stage II-IIIb). Am J Clin Oncol. 1991 Oct;14(5):427–432. doi: 10.1097/00000421-199110000-00013. [DOI] [PubMed] [Google Scholar]

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