A dose-escalation study of pegylated liposomal doxorubicin and oxaliplatin in patients with advanced solid tumors

Purpose: A phase I study was conducted to determine the maximum tolerated doses ( MTDs) and dose- limiting toxicities ( DLTs) of the pegylated liposomal doxorubicin ( PLD) and oxaliplatin combination in patients with advanced solid tumors. Patients and Methods: Forty- five patients with advancedstage solid tumors received escalating doses of PLD 25 - 50 mg/ m(2) as 60- min intravenous ( i. v.) infusion and oxaliplatin 80 - 130 mg/ m(2) as 2- to 4- hour i. v. infusion on day 1 every 3 weeks without growth factors. Results: MTD was defined at PLD 45 mg/ m(2) and oxaliplatin 130 mg/ m 2. Eleven dose levels were evaluated and DLTs were grade 2 - 3 neutropenia resulting in treatment delays, grade 3 neurotoxicity and nausea/ vomiting. A total of 187 cycles were administered with two episodes of febrile neutropenia and one toxic death due to sepsis. Two ( 4%) and 6 ( 13%) patients developed grade 4 and 3 neutropenia, respectively, 2 ( 4%) and 1 ( 2%) grade 4 and 3 thrombocytopenia, and 1 ( 2%) grade 4 anemia. The most common nonhematological toxicities were grade 2 - 3 nausea/ vomiting and asthenia observed in 27 ( 60%) and 16 ( 36%) of patients, respectively. One complete and eight partial responses were observed. Conclusion: The combination of PLD and oxaliplatin has an acceptable toxicity profile with promising activity and merits further evaluation in phase II studies.