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

ABSTRACT

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 x 10(9) l(-1) and the platelets > 75 x 10(9) 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.