Phase I study of a biweekly schedule of a fixed dose of cisplatin with increasing doses of paclitaxel in patients with advanced oesophageal cancer

We performed this dose-finding study with a fixed dose of cisplatin and increasing doses of paclitaxel given every 2 weeks to determine the maximum tolerable dose of this schedule. Sixty-four patients with advanced oesophageal cancer were treated with a cisplatin dose of 60 mg m−2 and increasing doses of paclitaxel from 100 mg m−2 up to 200 mg m−2 both administered over 3 h for a maximum of six cycles in patients with stable disease or eight cycles in responding patients. Patients were retreated when the granulocytes were > 0.75 × 109 l−1 and the platelets > 75 × 109 l−1. The dose of paclitaxel could be increased to 200 mg m−2 without encountering dose limiting haematological toxicity. At the dose levels 190 mg m−2 and 200 mg m−2 of paclitaxel cumulative sensory neurotoxicity became the dose-limiting toxicity. The dose intensity of paclitaxel calculated over six cycles rose from 50 mg m−2 per week to 85 mg m−2 per week. Only three episodes of granulocytopenic fever were encountered out of a total of 362 cycles of treatment. Of the 59 patients evaluable for response, 31 (52%) had a partial or complete response. In a biweekly schedule with a fixed dose of 60 mg m−2 cisplatin it is possible to increase the dose of paclitaxel to 180 mg m−2. At higher dose levels, neurotoxicity becomes the dose-limiting toxicity. The observed response rate warrants further investigation of this schedule. © 1999 Cancer Research Campaign