Therapy of patients with squamous cell carcinoma and adenocarcinoma of the esophagus or gastroesophageal junction with paclitaxel.

Metastatic or local-regional unresectable carcinoma of the esophagus or gastroesophageal junction results in a dismal prognosis. Most patients, succumb to either locally advancing disease or progressive widespread metastases. Chemotherapeutic agents given as single agent or in combination often result in either no benefit or only transient palliation. New active agents are needed to improve the outcome of these patients. A phase II NCI-sponsored study of Paclitaxel was conducted at UT M.D. Anderson Cancer Center, Houston, Texas and Memorial Sloan-Kettering Cancer Center, New York, simultaneously. Eligible patients included those with unresectable local-regional or metastatic carcinoma of the esophagus or gastroesophageal junction. The purpose of the study was to evaluate response rate, duration of response, and toxicity. Prior chemotherapy or biologic therapy was not alllowed. Patients with either squamous cell carcinoma or adenocarcinoma were eligible for this study. The starting dose of Paclitaxel was 250 mg/m2 administered by a 24-hour IV infusion repeated every 21 days. All patients were premedicated with dexamethasone, cimetidine, and diphenhydramine hydrochloride. In addition, all patients received granulocyte-colony stimulating factor(G-CSF; 5 mug/Kg)s.c. daily 24 hours after the completion of Paclitaxel to reduce the duration and severity of granulocytopenia. Fifty-three patients were registered. Two patients were inevaluable since they did not receive Paclitaxel. Fifty-one patients were assessable for response and response duration. Thirty-three patients had adenocarcinoma and 18 had squamous cell carcinoma. Forty-four patients were men and 6 were women. The median age was 57 years(range, 36 to 77 years). The median Zubrod PS was 1(range, 1 to 2). The median no. of courses was 4(range, 1-14+; total courses 229). The dose was reduced in 53 courses and increased in 15. Sixteen(32 percent) patients achieved a response(one complete and 15 partial) and eleven(22 percent) achieved a minor response. Among 33 patients with adenocarcinoma, 12(36 percent; 95 percent Confidence Interval, 14 percent to 58 percent) achieved either a complete(one patient)or partial resposne(11 patients) and 6 patients had a minor response. Four(22 percent; 95 percent Confidence Interval, 3 percent to 41 percent) of 18 patients with squamous cell carcinoma had a partial response and 4 (22 percent) had a minor response. The median duration of partial response was 17 weeks(range, 7 to 58 weeks). At a median follow up of 12+ months, 28 patients remain alive with an actuarial median survival duration of 10.2 months (range, 2 months to 20+ months). Paclitaxel was well tolerated. Granulocytopenia was frequent resulting in 11 hospitalizations in 9 patients in 9 patients. Grade 3 neuropathy was observed in three patients. Our data suggest that Paclitaxel is an active agent against adenocarcinoma as well as squamous cell carcinoma of the esophagus. Plans to study Paclitaxel in combination with cisplatin and 5-fluorouracil in this group of patients are underway.