Pegylated liposomal doxorubicin and cyclophosphamide in early recurrent ovarian carcinoma: phase I dose-finding study.

PURPOSE: This single-arm phase I dose-escalation study determines the optimal dose of the non-platinum treatment pegylated liposomal doxorubicin (PLD) plus cyclophosphamide (CPM) every 4 weeks in early recurrent ovarian carcinoma.

METHODS

Twenty-one women with ovarian carcinoma relapsing within 12 months of first-line surgery and platinum-taxane chemotherapy received escalating doses of PLD (35-45 mg/m(2)) and CPM (500-600 mg/m(2)) every 4 weeks for at least two cycles. Primary objective was assessment of maximum-tolerated dose (MTD) over the first two cycles. Secondary objectives were to assess safety over 2 cycles, efficacy evaluated every two cycles (response evaluation criteria in solid tumours criteria) and overall survival (OS).

RESULTS

The PLD-CPM MTD was 40/600 mg/m(2) with 2/3 patients treated at 45/500 mg/m(2), showing DLTs with Grade 3/4 oesophagitis, thrombopenia/neutropenia, leucopoenia, and Grade 3 stomatitis/asthenia during the first cycle of treatment. Four severe toxicities were reported by three patients during the two first cycles, namely Grade 4 anaemia, and Grade 3 stomatitis. The most common treatment-related toxicities were anaemia (71.4 %), nausea (61.9 %), neutropenia (57.1 %), asthenia (52.4 %), leucopoenia (47.6 %), stomatitis (42.9 %), skin (28.6 %) and palmar-plantar-erythrodysesthesia (19 %). No treatment-related deaths were reported. The overall response rate (complete and partial) was 31 %, and median OS was 8.2 months [95 % CI (3.3-13.2)].

CONCLUSIONS

The combination of PLD and CPM is feasible and may be considered particularly in cases where platinum-based treatment is not suitable. The recommended doses for a phase II trial are PLD 40 mg/m(2) plus CPM 600 mg/m(2) every 4 weeks.