Phase I study of MEN-10755, a new anthracycline in patients with solid tumours: a report from the European Organization for Research and Treatment of Cancer, Early Clinical Studies Group.

A phase I study was performed with MEN-10755, a novel anthracycline with promising preclinical antitumour activity, in patients with solid tumours to determine the maximum tolerated dose (MTD); the dose-limiting toxicities (DLTs); to document antitumour activity; and to propose a safe dose for phase II evaluation. MEN-10755 at a starting dose of 15 mg/m2/week was given by short intravenous infusion weekly for 3 weeks and cycles were repeated every 28 days. Twenty-four patients received 55 cycles. Doses of MEN-10755 were 15, 30, 40 and 45 mg/m2. At a dose of MEN-10755 45 mg/m2, treatment could not be given as planned due to neutropenia and one patient developed a decrease in cardiac function. This dose level was considered to be the MTD. Chemotherapy-naive patients could be treated with 40 mg/m2/week, and only one DLT (grade 4 neutropenia) was observed. At that dose, three of six chemotherapy pretreated patients developed a DLT during their first treatment cycle: one patient developed a grade 4 thrombocytopenia, one patient a grade 4 neutropenia and one patient developed a grade 3 acute hypersensitivity reaction resulting in discontinuation of treatment. At this dose level, one other patient did not receive treatment on day 15 as planned due to grade 3 neutropenia. No responses were observed. MEN-107555 at a dose of 30 mg/m2/week in pretreated patients and 40 mg/m2/week in chemotherapy-naive patients for three consecutive weeks followed by 1 week rest is recommended for phase II testing.