Combination of cytostatics and radiation--a new trend in the treatment of inoperable esophageal cancer.

The prognosis of patients with squamous cell carcinoma of the esophagus remains dismal, in spite of technical advances in both surgery and radiation therapy. Chemotherapy as a palliative approach is still in the investigational phase and the very moderate antitumor activity has been observed with only a few single agents (Bleomycin, Adriamycin, Cis Platinum, 5-Fluorouracil, Vindesine). In an attempt to improve therapeutic results, cytostatic agents, which interacts with radiation, are now combined with radiotherapy. In a sequential manner several controlled clinical studies were performed in more than 250 patients, using antitumor drugs alone or in combination with radiation. The results of these studies showed superiority of combined approach, either in remission rate or remission duration. Combination of Bleomycin + radiation achieved a response rate of 62%, Adriamycin + radiation 60%, while both drugs combined with radiation showed the same response rate but higher toxicity. By adding 5-Fluorouracil to Adriamycin/Bleomycin + radiation therapy, 64% and even 75% responses were observed compared to only 30-40% with cytostatics alone. With combined approach a median remission duration of 16 months was reached. An ongoing clinical trial, based upon in vitro proved synergism of 4-epi-doxorubicin and radiation, showed very promising results. Namely, this new analogue of Adriamycin, when combined with radiation, resulted in 6 complete and 7 partial remissions out of 17 patients entered the study (13/17 - 76%). Furthermore, 4 patients showed a minor regression (less than 50%), and no progression was observed. The advantages of chemoradiotherapy in esophageal cancer could be summarized as follows: higher response rate (60-80%), higher proportion of complete responses (up to 45%), longer remission duration, lower radiation dosage (3,200-4,000 cGy) and consequently better tolerance of treatment (less morbidity). The longer follow up will show, whether combined approach could increase 5-year survival rate of these patients.