CONTINUOUS HYPERFRACTIONATED ACCELERATED RADIOTHERAPY WITH WITHOUT MITOMYCIN-C IN HEAD AND NECK-CANCER/

Purpose: To evaluate the effect of mitomycin C to an accelerated hyper fractionated radiation therapy. The aim was to test a very short sched ule with/without mitomycin C (MMC) with conventional fractionation in histologically verified squamous cell carinoma of the head and neck re gion. Methods and Materials: From October 1990 to December 1996, 188 p atients entered the trial. Tumors originated in the oral cavity in 54, oropharynx in 82, larynx in 20, and hypopharynx in 32 cases, respecti vely. Patients' stages were predominantly T3 and T4 (158/188, 84%) and most patients had lymph node metastases (144/188; 77%) at diagnosis. Only 22 patients were female, 166 were male, the median age of patient s was 57 years (range 34 to 76 years). Patients were randomized to one of the following three treatment options: conventional fractionation (CF) consisting of 70 Gy in 35 fractions over 7 weeks (65 patients) or continuous hyperfractionated accelerated radiation therapy (V-CHART; 62 patients) or continuous hyperfractionated accelerated radiation the rapy with 20 mg/sqm MMC on day 5 (V-CHART + MMC; 61 patients). By the accelerated regimens, the total dose of 55.3 Gy was delivered within 1 7 consecutive days, by 33 fractions. On day 1, a single dose of 2.5 Gy was given, from day 2 to 17 a dose of 1.65 Gy was delivered twice: th e interfraction interval was 6 hours or more. Results: Mucositis was v ery intense after accelerated therapy, most patients experiencing a gr ade III/IV reaction. The mucosal reaction did not differ whether MMC w as administered or not. Patients treated by accelerated fractionation experienced a confluent mucosal reaction 12-14 days following start of therapy and recovered (no reaction) within 6 weeks. The skin reaction was not considered different in the three treatment groups. Those pat ients treated with additional chemotherapy experienced a grade III/IV hematologic toxicity in 12/61 patients. Initial complete response (CR) was recorded in 43% following CF, 58% after V-CHART, and 67% after V- CHART + MMC, respectively (p < 0.05). Actuarial survival (Kaplan-Meier ) was significantly improved in the combined treated patients. Local t umor control was 28%, 32%, and 56% following CF, V-CHART, and V-CHART + MMC, respectively (p < 0.05). Conclusion: We conclude that our conti nuous hyperfractionated accelerated radiation therapy regimen is equal to conventional fractionation, suggesting that by shortening the over all treatment time from 7 weeks to 17 days a reduction in dose from 70 Gy to 55.3 Gy is possible, with maintenance of local tumor control ra tes. The administration of MMC to the accelerated regimen is tolerable and improves the outcome for patients significantly. (C) 1998 Elsevie r Science Inc.