The use of mitomycin in esophageal cancer

Concurrent administration of chemotherapeutic agents and radiation with or without surgery has yielded better local disease control and more prolonged survival than has standard radiation therapy or surgery alone 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 rates of 14-42% in patients with squamous cell carcinoma of the esophagus. The response of patients with esophageal adenocarcinoma to single-agent mitomycin is unknown. The clinical use of mitomycin concurrent with 5-FU and radiation is well established in esophageal cancer. There is 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 use of mitomycin with radiation is additive or supra-additive as experimental evidence exists to support both types of interaction. Nonrandomized clinical trials suggest that using either cisplatin or mitomycin concurrently 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 toxicity is frequently severe if all 3 drugs are used concurrently in combination with radiation. In patients with advanced disease (stage III or IV), combination chemotherapy/radiation therapy can result in significant palliation with tolerable morbidity. The use of concurrent chemotherapy and radiation has changed the pattern of failure in esophageal cancer from one dominated by inability to control local disease to one where systemic failure predominates. Current and proposed trials in esophageal cancer have changed their focus accordingly to meet this new treatment challenge.