High-dose epirubicin for untreated patients with advanced tumours: a phase I study.

In a phase I study, epirubicin was administered as an intravenous bolus at an initial dose of 105 mg/m2 in untreated patients with advanced tumours considered resistant to antineoplastic treatment. A 15 mg/m2 dose escalation was done every 3 patients if toxicity was below grade 3 or every 6 patients if at least 1 patient had grade 3 toxicity. 18 patients entered the study. The dose was (mg/m2): 105 (3 patients), 120 (3), 135 (3), 150 (6) and 165 (3). The maximally tolerated dose was 165 mg/m2. The dose-limiting toxicity was neutropenia. Other side-effects were nausea/vomiting (78%) and alopecia (100%). 4 patients stopped treatment because of a decrease in left ventricular ejection function, without clinical signs of cardiotoxicity. A complete response was observed in a patient with abdominal metastases from unknown origin at 105 mg/m2 and a partial response in 2 out of 7 patients with non-operable non-small cell lung cancer, at 135 and 150 mg/m2, respectively. The recommended dose for phase II trial is 135-150 mg/m2.