Phase II clinical trial of 13-cis-retinoic acid and interferon-alpha-2a inpatients with advanced esophageal carcinoma

BACKGROUND. Interferon in combination with 5-fluorouracil has been shown to be active in squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus. 13-cis-retinoic acid (CRA) has chemopreventive activity in SCC o f the head and neck, and, in combination with interferon, has antitumor act ivity in SCC of the skin and cervix. METHODS. The activity and toxicity of CRA and interferon-alpha-2a (IFN) in patients with advanced esophageal carcinoma was evaluated in a Phase II sin gle institution trial. Patients had unresectable or metastatic AC or SCC of the esophagus. One prior chemotherapy regimen was allowed. IFN was given b y daily subcutaneous injection at a dose of 3 million U and CRA was taken o rally at a dose of 1 mg/kg/day in 2 divided doses. Treatment was given in c ycles of 4 weeks and continued until documented disease progression. RESULTS. Of the 19 patients entered, 15 were evaluable for response and tox icity. One patient was evaluable for response only and one patient was eval uable for toxicity only. Evaluable patients were predominantly male (15 pat ients), and had AC (13 patients). All had AJCC Stage IV disease and 12 were pretreated. Patients completed an average of two cycles of therapy (range, one to six cycles) prior to progression of disease. National Cancer Instit ute Common Toxicity Criteria Grade 3/4 toxicity was notable for nausea (25% ) and fatigue (31%). No major objective responses were recorded. Eleven pat ients with AC and 3 patients with SCC had rapid progression of disease. One patient with AC was found to have a minor response for 22 weeks and 1 pati ent with AC had stable disease for 45 weeks. CONCLUSIONS. This regimen had no significant activity in patients with adva nced AC of the esophagus. Further evaluation of IFN plus CRA, using this do se and schedule, is not recommended. In comparison with prior trials of thi s therapy, a surprising amount of severe nausea and fatigue was observed in this trial. Cancer 1999;85:1213-7. (C) 1999 American Cancer Society.