PACLITAXEL, IFOSFAMIDE AND CISPLATIN WITH GRANULOCYTE-COLONY-STIMULATING FACTOR OR RECOMBINANT HUMAN INTERLEUKIN-3 AND GRANULOCYTE-COLONY-STIMULATING FACTOR IN OVARIAN-CANCER - A FEASIBILITY STUDY

The tolerability and efficacy of four courses of paclitaxel and ifosfa mide plus cisplatin every 3 weeks was evaluated in patients with resid ual or refractory ovarian cancer. Additionally, supportive haematologi cal effects of recombinant human interleukin 3 (rhIL-3) and recombinan t human granulocyte colony-stimulating factor (G-CSF) were studied. Pa clitaxel starting dose was 135 mg m(-2) (day 1), with ifosfamide dose 1.2 g m(-2) day(-1) (days 2-4) and cisplatin dose 30 mg m(-2) day(-1) (days 2-4). All 16 patients received 5.0 mu g kg(-1) day(-1) G-CSF (da ys 7-16) and, in addition, eight patients were randomized to receive 1 0 mu g kg(-1) day(-1) rhIL-3 (days 5-9). Paclitaxel and ifosfamide dos es were reduced when grade IV haematological toxicity occurred. In the absence of grade IV haematological toxicity and normal recovery of ha ematopoiesis, paclitaxel dose was escalated. Toxicity was evaluable in 56 courses, with haematological effects in 52. Despite antiemetic tre atment, nausea and vomiting (greater than or equal to grade I) occurre d in 50 courses. Five patients had persisting peripheral neuropathy. R enal and liver function were not affected. Grade IV neutropenia occurr ed in 12 out of 52 courses, with neutropenic fever in two patients, bo th of whom died from fatal septicaemia. Grade IV thrombocytopenia with out bleeding was observed in 15 courses. Grade IV haematological toxic ity was associated with hepatic metastases and concurrent increases in alkaline phosphatase (P <0.001) and gamma-glutamyltransferase (P=0.00 7). No relation was found between haematological toxicity and pharmaco kinetic parameters of paclitaxel. Patients treated with rhIL-3 showed a tendency to a faster platelet recovery (not affecting platelet nadir ), and the cisplatin dose intensity was higher (P=0.025). Six of the n ine evaluable patients had a tumour response. The overall median progr ession-free survival was 7 months and the overall mean survival was 13 months. In conclusion, this potentially interesting combination as se cond-line treatment showed a low tolerability with unexpected mortalit y, while rhIL-3 administration tended to induce a more rapid platelet recovery.