A PILOT-STUDY OF A NEW THERAPEUTIC APPROACH IN THE TREATMENT OF LOCALLY ADVANCED STAGES OF RECTAL-CANCER - NEOADJUVANT RADIATION, CHEMOTHERAPY AND REGIONAL HYPERTHERMIA

The synergistic effects of hyperthermia (temperatures greater than or equal to 41 degrees C) when combined with radiotherapy or cytotoxic dr ugs, as well as a modulation of tumour-related immunological phenomena have been demonstrated preclinically. Local or regional hyperthermia in combination with radiation or chemotherapy has been studied in pati ents during recent years, and has convincingly demonstrated that hyper thermia is feasible and tolerated by patients. Furthermore, there is s trong evidence that hyperthermia may provide an improvement in local c ontrol as compared with radiotherapy or chemotherapy alone. Systems ba sed on radiowave irradiation allow sufficiently tolerable and effectiv e regional hyperthermic therapy in patients with rectal carcinomas. Us ed as part of curative pre-operative and postoperative multimodal ther apeutic strategies in high-risk patients with locally advanced rectal carcinomas, hyperthermia may result in improved local control and a hi gher rate of sphincter-sparing procedures. 20 patients with non-resect able, locally advanced primary or recurring rectal carcinoma T3/4 ente red a phase I/II study of pre-operative radiochemothermotherapy with f olinic acid and 5-fluorouracil, radiation (45 Gy HD), as well as regio nal hyperthermia once a week followed by chemotherapy after surgery. T he regimen proved to be sufficiently tolerable. Acute grade III or IV toxicities did not occur after hyperthermia. Tumour resections were pe rformed on 14 of the 20 patients, with 13 being complete. In 9 of the carcinomas, downstaging compared with the pretherapeutic stage was ach ieved. In 3 of 6 patients with persistent non-resectable tumours, loca l control has now been maintained for more than 12 months. One patient progressed locally during neoadjuvant combination therapy. These resu lts prompted the initiation of a prospective randomised study to evalu ate the relative importance of regional hyperthermia in this setting.