A phase II trial of paclitaxel and cisplatin in patients with advanced carcinoma of the esophagus

PURPOSE In a phase II trial of paclitaxel, cisplatin, and fluorouracil in metastatic esophageal cancer, we identified significant activity for the combination of agents, but there was severe associated toxicity. We therefore undertook a phase II trial of paclitaxel and cisplatin without fluorouracil. PATIENTS AND METHODS Thirty-eight patients with carcinoma of the esophagus or gastroesophageal junction were treated. No patient who underwent prior chemotherapy was allowed to take part in the study. The majority (33 patients) had adenocarcinoma, and most (36 patients, 95%) had metastatic disease. Paclitaxel, 200 to 250 mg/ m(2), was given by 24-hour infusion on day 1, followed by cisplatin, 75 mg/m(2), on day 2, with granulocyte colony stimulating factor support. Treatment was cycled every 21 days in the outpatient setting. The first 16 patients received paclitaxel at 250 mg/m(2), but because of toxicity and treatment-related deaths, the dose was reduced to 200 mp/m(2). RESULTS Thirty-two patients were evaluable for response. Six patients were evaluated for toxicity after receiving only one cycle (due to toxicity or treatment-related death). Partial responses were seen in 14 patients (44%); responses occurred in 13/28 patients with adenocarcinoma (46%) and in one of four patients with squamous carcinoma (25%). Median duration of response was 3.9 months, and median survival was 6.9 months. Of twenty-five patients with dysphagia before therapy, eighteen patients (72%) had complete resolution of dysphagia, and two (8%) had partial resolution. Toxicity included grade 3/4 fatigue in 35% of patients and grade 4 neutropenia in 47% of patients. Nineteen patients (50%) required hospitalization for toxicity, and four patients (11%) died from therapy-related complications. CONCLUSION The combination of paclitaxel and cisplatin has significant activity in esophageal adenocarcinoma. Because of hospitalization for toxicity and deaths resulting from treatment, the combination of paclitaxel and cisplatin used in this trial cannot be recommended. The optimal dose and schedule of paclitaxel/cisplatin combination therapy remain to be established.