543 Pegylated Liposomal Doxorubicin and Vinorelbine Combination in Advanced Heavily Pretreated Ovarian Cancer: A Phase II and Pharmacokinetic Study

Pegylated liposomal doxorubicin (PLD) and Vinorelbine (VNR) are active cytotoxic drugs in previously treated ovarian cancer patients (RR of 25% and 16-29% as single agents, respectively). We enrolled (02/2001-10/2002) 32 patients in a multicenter phase II study of the association of PLD 30 mg/sqm and VNR 30 mg/sqm q3wks for six cycles. Pharmacokinetic profile of VNR was determined in 6 patients (3 received the drugs in the sequence PLD-VNR-group A, and 3 in the reverse sequence-group B). 30 patients (19 FIGO stage IIIc, and 11 stage IV) were evaluated for response and toxicity. All patients had been previously treated with platinum-based regimens (median 2, range 1-6). Toxicity was generally mild and reversible. G3 toxicity included neutropenia in 4, fatigue in 3 and PPE in 1 course. One patient stopped treatment because of G3 stomatitis, and two for allergic reaction. No toxic death was reported. ORR after 6 cycles was 36.7% (1 CR and 10 PR). Median TTP and OS were was 5.5 months (range 1-10) and 9 months (range 2-16), respectively. VNR serum levels in schedule B (Cmax 835 ng/ml) was in agreement with that found in literature for VNR in monotherapy, while in group A it was twice as much that in schedule B (Cmax 1758 ng/ml). The difference may be due to the inhibition of the P-glycoprotein by liposomal components that cause a reduction of the VNR elimination. Combination chemotherapy with PLD-VNR is feasible, safe, with low toxicity profile and better response rate compared to single agent alone.