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The synergistic activity observed in vitro in V-79 hamster lung cells after treatment with 4-epi-doxorubicin (4-epi-DX) combined with irradiation stimulated a pilot study of 38 patients with inoperable locoregionally advanced squamous cell esophageal cancer. The patients (30 males, 8 females; mean age 60 years) had undergone no prior radiation or cytostatic drug therapy. Twenty tumors were localized in the middle third of the esophagus, and the remainder in the upper or lower third. Histological evidence of the tumor was obtained in all patients before treatment by endoscopy. The 33 evaluable cases included 30 squamous cell carcinomas, 2 anaplastic (squamous cell) carcinomas and 1 adenocarcinoma. The patients were irradiated in two opposite thoracic fields (Betatron-Siemens) with a total dosage of 3600-4000 cGy (200 cGy daily, 1000 weekly). The patients were concurrently administered 4-epi-DX at the dose of 50 mg/m2i.v. daily on days 1, 2, 22 and 23; the total 4-epi-DX dosage was 200 mg/m2. The results showed that 4-epi-DX combined with irradiation had a pronounced antitumorigenic activity, since the 33 evaluable patients included 11 complete and 12 partial remissions, with a response rate of 70% (23/33). A minor regression (< 50%) was observed in 6 cases, and progression of the disease in 4. The median duration of the remissions was 9 + months (14 + months in complete responders). In 8 patients with a complete clinical response even the endoscopic biopsy samples were negative. Toxicity was moderate and reversible, and mainly accounted for by radiation mucositis and retrosternal pain, alopecia and mild bone marrow suppression. Transient ECG changes were observed in 3 cases. The results of the pilot study show that the combination of 4-epi-DX and irradiation might constitute successful palliative treatment for squamous cell esophageal cancer.

The purpose of this study was to test the type and the degree of cytotoxic effects of epirubicin and radiation in combined treatment on Chinese hamster lung cells in vitro. Experiments were performed with proliferating tissue culture cells. Cell kill was determined by colony-forming ability. The maximum killing effects were obtained when simultaneous action of drug treatment and irradiation occurred. Their interaction was synergistic. Synergism depended on time of drug incubation (epirubicin present for 1 h). Slight antagonism was noted after prolonged drug action (24 h).