Phase I/II trial of etoposide and carboplatin in extensive small-cell lung cancer. A report from the Cancer and Leukemia Group B.
Previously untreated extensive small-cell lung cancer (SCLC) patients with performance status 0-2 were treated with etoposide 200 mg/m2/day on days 1-3 and carboplatin doses of 50, 100, or 125 mg/m2/day on days 1-3 in a Phase I format. Among the ten eligible patients treated with 125 mg/m2/day of carboplatin, grade 3 or 4 infection occurred in six patients, grade 4 thrombocytopenia in four patients, and there was one death with myelosuppression. Thus, this dose was considered the maximum tolerated dose (MTD), and a Phase II trial was then conducted utilizing this treatment program. In the Phase II trials, 81% of the 48 eligible patients had grade 3 or 4 leukopenia, 76% had grade 3 or 4 thrombocytopenia, and 55% had grade 3 or 4 anemia. There were three (6%) toxic deaths from myelosuppression. The objective response rate was 63% (17% complete responders) with a median response duration of 6.2 months for complete responders and 6.4 months for partial responders. Median survival was 12 months. The MTD defined by this Phase I trial represents a 67-100% increase in etoposide and a 25% increase in carboplatin compared to prior studies. Cancer and Leukemia Group B (CALGB) plans to study further dose intensification of this regimen with colony-stimulating factors.
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.
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Luikart
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Goutsou
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Mitchell
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Van Echo
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Modeas
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Propert
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O'Donnell
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Difino
M C
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Perry
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Green
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis
D005047:Etoposide; D016190:Carboplatin