THE USE OF MITOMYCIN IN ESOPHAGEAL CANCER

Concurrent administration of chemotherapeutic agents and radiation wit h or without surgery has yielded better local disease control and more prolonged survival than has standard radiation therapy or surgery alo ne in patients with esophageal cancer. Combinations of 5-fluorouracil (5-FU) and either cisplatin or mitomycin have proven most effective in this setting. As a single agent, mitomycin has generated response rat es of 14-42% in patients with squamous cell carcinoma of the esophagus . The response of patients with esophageal adenocarcinoma to single-ag ent mitomycin is unknown. The clinical use of mitomycin concurrent wit h 5-FU and radiation is well established in esophageal cancer. There i s some experimental evidence to suggest that synergy may occur between 5-FU and mitomycin. Mitomycin is preferentially cytotoxic to hypoxic cells, which are relatively radioresistant. It is not clear whether us e of mitomycin with radiation is additive or supra-additive as experim ental evidence exists to support both types of interaction. Nonrandomi zed clinical trials suggest that using either cisplatin or mitomycin c oncurrently with 5-FU and relatively low-dose radiation (30 Gy) prior to esophagectomy can result in comparable rates of pathologic complete response (20-30%) and median survival (12-19 months). Hematologic tox icity is frequently severe if all 3 drugs are used concurrently in com bination with radiation. In patients with advanced disease (stage III or IV), combination chemotherapy/radiation therapy can result in signi ficant palliation with tolerable morbidity. The use of concurrent chem otherapy and radiation has changed the pattern of failure in esophagea l cancer from one dominated by inability to control local disease to o ne where systemic failure predominates. Current and proposed trials in esophageal cancer have changed their focus accordingly to meet this n ew treatment challenge.