Background: In a previous phase I study we showed that single-agent cisplatin can be given weekly for six weeks at a dose of 80 mg/m2/wk. It has been suggested that etoposide has synergistic activity with cisplatin and the drug can be given orally continuously. We therefore performed a phase I study with weekly cisplatin combined with oral etoposide.
Patients and methods: Nineteen patients with metastases of a solid tumor were entered in the study. Cisplatin was administered in hypertonic saline (NaCl 3%). Etoposide was administered as 50-mg capsules.
Results: The starting dose was cisplatin weekly at a dose of 70 mg/m2 for six weeks combined with daily oral etoposide at a dose of 50 mg. At the maximum tolerable dose of cisplatin 75 mg/m2/wk and etoposide 50 mg/m2 daily, leukocytopenia and thrombocytopenia were dose-limiting toxic effects which resulted in frequent treatment delays. Other toxicities were mild. Finally, a dose of cisplatin 70 mg/m2/wk weeks 1-2-3 and weeks 5-6-7 in combination with etoposide 50 mg orally days 1-15 and days 29-43 combined a high median cisplatin dose intensity of 52.5 mg/m2/wk with a good patient tolerance.
Conclusion: It is feasible to administer frequently dosed cisplatin in combination with oral etoposide. Leukocytopenia and thrombocytopenia are dose-limiting toxicities. The schedule will be explored further in phase II studies.