A phase I study of paclitaxel and epirubicin, without and with filgrastim,for the treatment of platinum-resistant advanced ovarian cancer

The aim of the study was to determine the maximum tolerated dose (MTD) of e pirubicin combined with a fixed dose of paclitaxel, without and with suppor t of filgrastim, in patients with platinum resistant or refractory ovarian cancer. Paclitaxel (150 mg/m(2)) and epirubicin (starting dose 90 mg/m(2), 15 mg/m(2) escalation per level) were given on day 1, every 28 days for 4-6 cycles. Filgrastim (F) (5 mu g/kg/die) was given in case of grade 4 leukop enia (levels without support) or from day 4 up to leukocyte count >10,000/m m(3) after nadir (levels with support). Cohorts of 3 patients were enrolled at each level and further 3 patients were planned if 1 or 2 unacceptable t oxic events (UTE) were registered. MTD was determined first without and the n with filgrastim. Four levels were studied (90, 90+F, 105+F, 120+F) with 4 , 6, 5 and 4 patients enrolled, respectively. UTE (grade 4 neutropenia) wer e observed in 3 patients at level 1. Thus, 90 mg/m(2) was the MTD for epiru bicin without filgrastim. MTD of epirubicin with filgrastim was not reached at 120 mg/m(2). Hematological toxicity was mild. Grade 3 mucositis was rep orted in 1 patient. Among the 14 patients with measurable or evaluable dise ase, 3 objective responses were observed (1 complete and 2 partial) for an overall response rate of 21.4%. The combination of paclitaxel 150 mg/m(2) a nd epirubicin at 120 mg/m(2) with filgrastim is a feasible therapy. Grade 4 leukopenia is the dose limiting toxicity using epirubicin at 90 mg/m(2) wi thout filgrastim.