Phase I study of pegylated liposomal doxorubicin (Caelyx) in combination with carboplatin in patients with advanced solid tumors.

ABSTRACT

PURPOSE: To determine the maximum tolerated dose of the combination of Carboplatin and Caelyx, a pegylated liposomal doxorubicin, with promising activities in various solid tumors. PATIENTS AND METHODS: Twenty-two patients with various advanced solid tumors were included. Three dose levels of Caelyx were explored 30, 35 and 40 mg/m2 in association with a fixed dose of Carboplatin (AUC 5) every 3 weeks. Dose escalation followed a modified continuous reassessment method. RESULTS: Dose-limiting toxicities were almost exclusively hematological 3 febrile neutropenia, 1 grade 4 neutropenia lasting more than 7 days and 2 grade 4 thrombopenia were observed. Grade 4 neutropenia and febrile neutropenia were observed in 20 and 10% of courses, respectively. The median interval between courses was 25 days after cycle 1 and 27-28 days after subsequent cycles. Palmar-plantar erythrodysesthesia, mucositis and other non hematological toxicities were mild and uncommon. One patient experienced a severe anaphylactic reaction immediately after Caelyx infusion. No clinical heart dysfunction was observed. Three patients responded to therapy including 2 clinical complete responses in relapsing ovarian cancer. CONCLUSION: The recommended dose for future studies is Caelyx 35 mg/m2 + Carboplatin AUC 5 every 3 or 4 weeks. Antitumor activity, especially in ovarian cancer, warrants further investigation in phase II studies.