The Value of Two Combined Chemoradiotherapy Approaches in the Treatment of Inoperable Esophageal Cancer

Abstract

The antitumor activity of 5-fluorouracil (5-FU), combined either with bleomycin or adriamycin plus radiation, was studied in a controlled randomized clinical trial. Sixty-one previously untreated inoperable esophageal cancer patients entered the study and 56 have been evaluated: 58 male and 3 female patints with a mean age of 57 years (range 37–74). Concerning localization of the tumors in the esophagus, 2 were in the upper third, 36 in the middle third and 18 in the lower third. The length of the filling defects in the esophagogram (X-ray) was in 9 patients < 5 cm, in 31 5–8 cm, and in 16 patients > 8 cm. Squamous cell carcinoma was found in 51 patients, adenocarcinoma in 3, and anaplastic (squamous cell) carcinoma in 2 patients. Modality A consisted of a combination of 5-FU (10 mg/kg i.v. 2 × weekly, 4 weeks) and bleomycin (10 mg/m² i.v., 2 × 4 weeks) which was given concurrently with radiation (3600–4000 rad - 1000 rad weekly). In modality B the combination of 5-FU (same dose) and adriamycin (30 mg/m² i.v. day 1, 2, 23 and 24) was applied with the same schedule and dosage of radiation. Seventy-five percent of the patients (21/28) have responded to treatment (CR + PR) in modality A, with 11 complete and 10 partial responses. In arm B, response was recorded in 64 % of patients (18/28), with 2 complete and 16 partial responses. The difference in complete responses (39 % vs 8 %) was statistically significant (P < 0.05). The median remission duration in complete responders was 12 months in modality A (range 6–18 months), and 6.8 months in modality B (range 3–10 months). All the responses occurred in patients with squamous cell carcinoma, except one partial response in a case of adenocarcinoma. As far as the age is concerned (< 55 vs > 55 years), no significant difference in response rate was found (67 % vs 71 %). More favorable results were observed in the group of patients with < 10 % weight loss (79 % vs 63 %). Toxicity was moderate (myelosuppression, cardiotoxicity), but one treatment-related death (pulmonary fibrosis, cardiac failure) was recorded in arm A, as well as one death (rupture of aorta) in group B. Approximately 60 % of patients in both modalities suffered from severe mucositis and retrosternal pain. The results of the study showed that the combination of 5-FU with adriamycin and particularly with bleomycin, given concurrently with lower radiation dosage, is an effective palliative treatment for inoperable esophageal cancer.