We performed a phase I study of a fixed dose of cisplatin combined with increasing doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given in a biweekly schedule to determine the maximum tolerated dose in patients with advanced esophageal cancer. The starting dose was cisplatin 60 mg/m2 and paclitaxel 100 mg/m2, given by intravenous infusion every 2 weeks. Patients were re-treated when the granulocyte counts were greater than 0.75 x 10(9)L and the platelet counts were greater than 75 x 10(9)/L. The paclitaxel dose has been escalated to 160 mg/m2 and the maximum tolerated dose has not yet been reached. At the higher dose levels, more grade 3 and 4 granulocytopenia was observed, but no patient had to be hospitalized because of febrile neutropenia. Nonhematologic toxicity was mild at all dose levels. Increasing the dose of paclitaxel from 100 mg/m2 to 160 mg/m2 leads to an approximately 50% increase in the dose intensity, as calculated in milligrams per square meter per week (mg/m2/wk) over six cycles. Of the 31 patients evaluable for response, 17 (55%) achieved either a partial or a complete response. In conclusion, biweekly administration of cisplatin and paclitaxel, with re-treatment at a granulocyte level greater than 0.75 x 10(9)/L, is feasible and well tolerated, and has a promising response rate in patients with advanced esophageal cancer. Further accrual is ongoing to determine the maximum tolerated dose of this schedule.