Randomized 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

C. A. Perez, L. Einhorn, R. K. Oldham, F. A. Greco, H. J. Cohen, H. Silberman, S. Krauss, N. Hornback, F. Comas, G. Omura

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Abstract

A total of 304 patients with limited small-cell carcinoma of the lung were treated with a combination of cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, Ohio), and vincristine (CAV) and elective brain irradiation (3,600 rad TD in 14 fractions). The patients were randomized to either receive or not receive thoracic irradiation (4,000 rad TD, split course). Of the 304 patients, 291 were eligible for the study. Two hundred eighteen (75%) were completeley evaluable. In each group, 81% of the patients had a Karnofsky index of 80% or higher and 14% had supraclavicular or scalene lymph nodes. Patients treated with CAV and no thoracic irradiation had a complete response (CR) of 48%, in contrast to 63% for those receiving chest irradiation (P=.05). In the first group, the complete and partial response rate was 70%; in the second, 80%. The median survival for the eligible patients treated with CAV and brain radiation therapy was 49 weeks; for those treated with the same regimen plus thoracic irradiation, the median survival was 60 weeks. The actuarial two-year tumor-free survival is 19% in the first group and 28% in the second group. The median survival for the responders in the CAV plus brain irradiation group was 57 weeks and for those receiving thoracic irradiation, 78 weeks (P=.12). Thoracic failure was 52% in patients not treated with thoracic radiation therapy v 36% in those receiving it (P=.06). The distant metastases incidence was 23% in patients not treated with thoracic radiation and 35% in patients treated with thoracic radiation. Hematologic toxicity was comparable in both groups; 30% of the patients had moderate to severe granulocytopenia and 6%, low homoglobin. Two toxicity-related deaths occurred (one in each group). Moderate gastrointestinal toxicity was noted in 41% and severe in 16% of the patients receiving CAV and brain irradiation without thoracic radiotherapy v 44% and 20% in those irradiated in the thorax. Disease-free survival is enhanced in the patients receiving thoracic irradiation. More effective chemotherapy is critically needed to significantly improve overall survival. These preliminary results suggest that thoracic irradiation should be a primary component in the therapy of these patients, although this combined therapy is moderately toxic. Additional clinical trials will be required to identify subpopulations of patients who will benefit the most with this approach, to determine the optimal time of administration of the irradiation and chemotherapy (concurrent v sequential schedules), and to identify technical parameters of irradiation combined with chemotherapy that will yield optimal therapeutic results.

Original languageEnglish (US)
Pages (from-to)1200-1208
Number of pages9
JournalJournal of Clinical Oncology
Volume2
Issue number11
DOIs
StatePublished - Jan 1 1984

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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