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 doselimiting 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.