Phase I study of pegylated liposomal doxorubicin, paclitaxel, and cisplatin in patients with advanced solid tumors

Background: The combination of doxorubicin, paclitaxel, and cisplatin has activity in gynecologic malignancies but requires colony stimulating factor (G-CSF) support. Moreover, there is concern about cardiotoxicity with doxorubicin/paclitaxel combinations. Pegylated liposomal doxorubicin may result in less myelosuppression and cardiac toxicity than free doxorubicin. The purpose of this study was to determine the maximal tolerated dose of pegylated liposomal doxorubicin with fixed doses of paclitaxel and cisplatin without using G-CSF support in advanced solid malignancies. Patients and methods:Twenty-three patients were enrolled; none of the patients had received prior doxorubicin. Patients received paclitaxel (90 mg/m(2) for dose level one, escalating to 135 mg/m(2) for all subsequent dose levels), with a fixed dose of cisplatin (60 mg/m(2)), followed by escalating doses of pegylated liposomal doxorubicin every 21 days. Results: A total of 73 cycles was administered. Grade 4 neutropenia was seen after cycle one in two of eight patients receiving 30 mg/m(2) of pegylated liposomal doxorubicin and three of seven patients receiving 40 mg/m(2) of pegylated liposomal doxorubicin when combined with 135 mg/m(2) of paclitaxel and 60 mg/m(2) of cisplatin. Two additional patients at the 40 mg/m(2) dose level developed grade 4 neutropenia following cycles 2 and 5. The mean decline in left ventricular ejection fraction (LVEF) after 2 cycles was 5 percentage points (P = 0.012). Conclusion: The combination of pegylated liposomal doxorubicin, paclitaxel and cisplatin is feasible without G-CSF support.