Cisplatin-topotecan-paclitaxel weekly administration with G-CSF support for ovarian and small-cell lung cancer patients:: A dose-finding study

Purpose. Paclitaxel (PTX) and topotecan (TPT) have shown promising antitumor activity in both ovarian cancer (OC) and small-cell lung cancer (SCLC) patients. This phase I study was aimed at determining the maximum tolerable dose (MTD) of TPT given weekly over 30 min in combination with fixed doses of cisplatin (CDDP) and (PTX), and with G-CSF support. Patients and methods: Forty-four patients with OC (19) or SCLC (25), either chemo-naive (20) or pretreated (24) received CDDP 40 mg/m(2), PTX 85 mg/m(2) (one-hour infusion) and escalating TPT doses (starting from 0.75 mg/m(2)) in a 30-min infusion in weekly administration. Filgrastim 5 mg/kg was administered on days 3 to 5 of each week. Results: Eight different dose levels were tested for a total of 295 delivered cycles. The dose escalation was interrupted at the TPT dose of 2.50 mg/m(2). No toxic deaths occurred in this study. Grade 3 to 4 neutropenia, thrombocytopenia, and anemia occurred in 15 patients (36 cycles), seven patients (15 cycles), and four patients (five cycles), respectively. Severe vomiting and diarrhoea occurred in seven and four patients. Peripheral neuropathy was recorded in 11 patients (42 cycles), but it was never severe. An overall 11 of 19 (58%) OC and 11 of 25 (44%) SCLC patients obtained objective responses. Eight patients showed complete responses (three OC and three SCLC). Among the 20 chemo-naive patients, 9 of 11 (82%) OC and seven of nine (78%) SCLC responded. Conclusions. The CDDP/TPT/PTX weekly administration with filgrastim support represents a well-tolerated and active therapeutic approach in both chemo-naive and pretreated OC and SCLC patients. A weekly dose of TPT of 2.25 mg/m(2) is recommended for the phase II study.