Concomitant continuous infusion chemotherapy and radiation

Attempts to duplicate the cytotoxic effect of oxygen on radioresistant tissues spurred a search by radiation oncologists for other radiosensitizing techniques. This led to large‐scale investigations using neutrons and other heavy particle radiations, hyperthermia, altered fractionation schedules, and the systemic use of the halogenated pyrimidines and the electron‐affinic compounds. Unfortunately, the promise that the nitroimidazole compounds would selectively sensitize the radioresistant tumor cells and prove to be an effective systemic agent has not been borne out in clinical trials thus far. Existing pharmokinetic and cytokinetic studies have suggested that continuous infusion chemotherapy given concomitantly (CCIC) with irradiation (RT) acts synergistically, resulting in a significant increase in tumor cell killing. These observations have been supported by clinical research studies treating certain epithelial cancers that have resulted in considerably higher locoregional control rates and improved survival. Although initially used in treatment of only advanced or inoperable epithelial carcinomas, CCIC and RT are now being employed in the treatment of lower staged cancers as an organ‐sparing procedure. Carcinoma of the anus treated by anteroposterior (AP) resection alone have reported 5‐year survival rates of 30% to 60%. CCIC and RT using 5‐fluorouracil (5‐FU) and mitomycin C have achieved a local control rate of 90% to 100% and a 5‐year survival rate of 80% to 86% with sphincter preservation in 90% of these cases. The 5‐year survival rate in advanced urinary bladder carcinoma is 25% to 30% for either radiation or surgery and 42% when combined in a preoperative radiation schedule. Using 5‐FU CCIC and RT, the local control rate of transitional cell carcinoma of the bladder has been 71% to 86% with a 5‐year survival of 62%. 5‐FU CCIC and cisplatin and RT used in the treatment of Stages III and IV carcinoma of the cervix yields a locoregional control of 74% compared with the radiation alone local control of 63% for Stage III and 30% for Stage IV disease. Advanced head and neck and paranasal sinus carcinomas treated by cisplatin CCIC and RT show improved tumor clearance even in the presence of bone destruction. A complete response rate of 87% has been reported with the use of cisplatin CCIC and hyperfractionated radiation. Hyperfractionated radiation also appears to improve the local control of advanced head and neck cancers over patients treated with single fractions of radiation with 66% surviving at 22 months. In carcinoma of the esophagus several trials with preoperative CCIC and RT using 5‐FU and mitomycin showed patients receiving 3000 cGy had a complete response rate of 25% at surgery, which increased to a 70% complete response at biopsy when 5000 cGy were delivered with the addition of 5‐FU and cisplatin. Such preliminary work requires further clinical trials to determine the best chemotherapeutic agent, dose fractionation, and required total dose for individual tumors.