A phase I study of chronic daily dosing of oral etoposide in combination with cisplatin for patients with advanced cancer

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Abstract
A dose escalation study of daily oral etoposide and cisplatin was carried out on 22 patients with advanced cancer using starting doses of 20 mg/m2/d of etoposide given orally for 21 days and 80 mg/m2 of cisplatin given intravenously (IV) on day 1. A total of 40 courses were given. Myelosuppression was the major dose‐limiting toxicity, with a maximum tolerated dose of 50 mg/m2/d of oral etoposide for 21 days plus 80 mg/m2 of IV cisplatin on day 1. Doses of 40 mg/m2/d of etoposide for 21 days plus 80 mg/m2 of cisplatin for 1 day in four of eight courses (50%) were associated with Grade 3 or worse leukopenia that occurred between days 18 and 26. However, no Grade 3 or worse thrombocytopenia occurred at this dose level. Nausea and vomiting occurred in most patients at each dose level but were mild and could be controlled by antiemetics. Alopecia also occurred frequently. Significant mucositis (Grade 4) occurred in one patient, but no other toxicities were observed. Four partial responses that lasted from 1.3 to 5.8+ months were observed in patients with cervical (one patient), small cell lung (one patient), and squamous cell lung cancer (two patients); one of them had been heavily pretreated with platin analogue‐containing regimens. The recommended doses for Phase II studies on this schedule are 40 mg/m2/d of oral etoposide for 21 days plus 80 mg/m2 of IV cisplatin on day 1. A combination regimen on this schedule seems particularly effective in patients with etoposide‐sensitive malignancies.