A phase I clinical and pharmacokinetic study (LIPOTEC - GP PHARM/DOXO 01) of a new liposomal doxorubicin given as 3-week schedule in patients with solid tumors

As a dose-finding phase I study of a new liposomal formulation of doxorubicin (LipD), patients (n = 39; median age: 60 years; range, 41-75; median ECOG performance status, 1; range, 0-2) with refractory cancer had a starting dose of LipD administered at 30 mg/m(2) as a 1-hour intravenous infusion. Cycle duration was 21 days. At the recommended dose (RD), patients received a first cycle of nonliposomal doxorubicin (non-LipD) to evaluate intrapatient pharmacokinetic differences between non-LipD and LipD. The most frequent diagnosis was head and neck tumor (7 patients). Tolerance and safety of dose levels of 30, 40, 50, 60, 70, 80, and 90 mg/m(2) were evaluated. A total of 131 cycles were administered (median per patient, 3; range, 1-6). Of the 39 patients, 8 completed the planned six cycles. Febrile neutropenia was dose limiting and defined the toxic dose of LipD as 70 mg/m(2). Other significant toxicities included asthenia (G2: 31%; G3: 8%), neutropenia (G3: 35%; G4: 29%), thrombopenia (G3: 15%; G4: 2%), anemia (G1-G2: 67%; G3-G4: 5%), mucositis (G1-G2: 32%, G3: 4%), and acute allergic reactions (G1-G2: 36%). Comparison of pharmacokinetic profiles of non-LipD and LipD showed that higher exposure was achieved with LipD. Stable disease was observed in 14 patients. We conclude that the LipD regimen, given as a 1-hour infusion every 3 weeks, is well tolerated and has a favorable pharmacokinetic profile. The recommended dose is 70 mg/m(2) with prophylactic antihistamines and corticoids to preempt allergic reaction.