CHEMOTHERAPY RAPIDLY ALTERNATING WITH TWICE-A-DAY ACCELERATED RADIATION-THERAPY IN CARCINOMAS INVOLVING THE HYPOPHARYNX OR ESOPHAGUS - AN UPDATE

Laboratory studies have suggested that rapidly alternating chemotherap y and radiation therapy might act synergistically. We undertook this s tudy to evaluate the toxicity and effectiveness of this approach in pa tients with carcinoma involving the hypopharynx or esophagus. Between 1987 and 1991, we treated 47 patients (23 with carcinoma involving the hypopharynx and 24 with carcinoma involving the esophagus) by three c ycles of chemotherapy (during weeks 1, 4, and 7) rapidly alternating w ith twice-a-day radiation therapy (during weeks 2, 5, and 8). Chemothe rapy consisted of cisplatin 100 mg/m(2) and 5-fluorouracil 3-4 g/m(2) given over 4 days. Radiation therapy consisted of 180-200 cGy twice ea ch day to 2000 cGy/cycle, total 6000 cGy over 7 week. The histology wa s squamous cell carcinoma in 44 patients and adenocarcinoma in 3 patie nts with esophagus cancer. Median follow-up is 2 years (range 1-5 year s). The observed survival rate for all 47 patients was 54% at 1 year a nd 38% at 2 years. Acute toxicity was considerable. Twelve patients (2 5%) died during therapy from toxicity, without tumor progression, leav ing 35 patients (18 hypopharynx, 17 esophagus) evaluable for response. Among the hypopharyngeal patients, 83% had a complete response, 11% h ad a partial response, and 6% had no response. Among the esophageal pa tients, 94% had a complete response, and 6% had a partial response. Lo cal control was better for the esophageal patients than the hypopharyn geal patients (98% vs. 52% at 2 years, p = 0.038). The incidence of di stant metastases was 25% at 2 years and not significantly different be tween the two groups. A high rate of local control was,as achieved, pa rticularly in esophageal cancer, by delivering chemotherapy and radiat ion therapy in a rapidly, alternating fashion. This was achieved at a considerable cost in terms of toxicity, however, Although our response rates and local control compare favorably with those of other recentl y published studies of combined modality therapy in esophagus or head and neck cancer, much additional work is required to reduce the toxici ty and, in hypopharyngeal cancer, to further improve the local control .