• D C Ihde, J L Mulshine, B S Kramer, S M Steinberg, R I Linnoila, A F Gazdar, M Edison, R M Phelps, M Lesar, and J C Phares.
• National Cancer Institute-Navy Medical Oncology Branch, Uniformed Services University of the Health Sciences, Bethesda, MD.
• J. Clin. Oncol. 1994 Oct 1; 12 (10): 2022-34.

PurposeWe performed a prospective randomized clinical trial to determine whether higher doses of etoposide and cisplatin (EP) yield more complete responses or longer survival in small-cell lung cancer (SCLC) patients.Patients And MethodsNinety patients with previously untreated extensive-stage SCLC fulfilled criteria for randomization to standard-dose versus high-dose EP. Another 25 patients at risk of excessive toxicity from high-dose treatment were given standard-dose therapy. During cycles 1 and 2 of EP, patients on standard-dose treatment received intravenous etoposide 80 mg/m2 on days 1 to 3 and cisplatin 80 mg/m2 on day 1 every 3 weeks; high-dose treatment consisted of etoposide 80 mg/m2 on days 1 to 5 and cisplatin 27 mg/m2 on days 1 to 5 every 3 weeks. All patients received standard-dose EP in cycles 3 and 4. In cycles 5 through 8, completely responding patients continued standard-dose EP; all other patients received either cyclophosphamide, doxorubicin, and vincristine, or (if possible) a combination drug program based on in vitro drug sensitivity testing of tumor-cell lines established from individual patients.ResultsDespite 68% higher doses and a 46% higher dose-rate intensity actually given to patients randomized to receive high-dose relative to those randomized to receive standard-dose EP, complete response rates (23% v 22%; P = .99) and median survival durations (10.7 and 11.4 months, respectively; P = .68) were virtually identical. Complete responses occurred in 4% of patients and the median survival duration was 5.8 months in nonrandomized patients. Leukopenia (P < .0001), thrombocytopenia (P < .0001), febrile neutropenia (P = .01), and weight loss (P = .02) were significantly more common in patients randomized to receive high-dose compared with standard-dose EP.ConclusionNo therapeutic benefits resulted from increasing planned doses by 67% for the first two cycles of EP in patients with extensive-stage SCLC. Higher doses were associated with substantially worse toxicities.

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