Phase II study of liposomal doxorubicin and weekly paclitaxel for recurrent Müllerian tumors

Pegylated liposomally encapsulated doxorubicin (Doxil. Ortho-Biotech) and paclitaxel (Taxol, Bristol Myers Squibb) are both active against Müllerian malignancies. A phase II trial was performed to determine the toxicity and efficacy of these agents when administered in combination.

Patients were initially treated with 30 mg/m(2) of liposomal doxorubicin every 21 days and 70 mg/m(2) of paclitaxel every week for 18 weeks. The plasma pharmacokinetics of paclitaxel was determined when administered alone and concurrently with liposomal doxorubicin.

Forty women with recurrent gynecologic malignancies of Müllerian origin including 34 with ovary and primary peritoneal cancer (85%) were enrolled. Toxicity was evaluated for all 508 cycles of therapy. Paclitaxel and liposomal doxorubicin were delivered at 95% (66.4 mg/m(2)/week) and 77% (7.65 mg/m(2)/week) of their intended weekly dose intensities, respectively. Reductions in the dose of liposomal doxorubicin were frequently required for palmar plantar erythrodysesthesia during the latter cycles of therapy. There were 4 patients with a complete response and 7 with partial responses, for an overall objective response rate of 29%, among the 38 evaluable patients. Response rates for the subset of 13 women with tumor recurrence occurring at least 6 months after prior platinum-based therapy was 54%. The concurrent administration of liposomal doxorubicin did not alter the pharmacokinetic disposition of paclitaxel.

Liposomal doxorubicin with weekly paclitaxel is active in Müllerian malignancies. The concurrent delivery of the weekly paclitaxel with liposomal doxorubicin may increase liposomal doxorubicin skin toxicity. Liposomal doxorubicin does not alter the pharmacokinetics of paclitaxel.