Accelerated RT + Mitomycin Improves Head & Neck Cancer

SAN ANTONIO—Accelerated radiation therapy given concomitantly with mitomycin C (Mutamycin) produced significantly improved results over standard radiation in patients with advanced head and neck cancer, Werner H. Dobrowsky, MD, reported at the at 41st Annual Scientific Meeting of the American Society for Therapeutic Radiology and Oncology.

Large, hypoxic tumors appeared to receive the most benefit from the addition of mitomycin. “Thus, mitomycin might overcome some of the problems due to hypoxia in head and neck cancers,” said Dr. Dobrowsky, of the Department of Radiotherapy and Radiobiology, University of Vienna.

The study included 229 patients, predominantly male (median age, 56), with squamous cell cancer of the head and neck region. Most had very advanced disease. “Most patients had actually been considered inoperable by the referring surgeons. About 85% had T3/T4 tumors, and almost 80% had lymph node metastasis,” he said.

This three-arm randomized trial was conducted between October 1990 and December 1997, and consisted of the following groups:

A conventional fractionation arm receiving 70 Gy in 35 fractions over 7 weeks.

An accelerated fractionation arm receiving 2.5 Gy on day 1 and two fractions of 1.65 Gy at least 6 hours apart on days 2 to 17, for a total dose of 55.3 Gy.

An accelerated fractionation arm as above with the addition of mitomycin given on day 5 at a dose of 20 mg/m².

The results with standard radiotherapy alone were comparable to those with hyperfractionated accelerated radiotherapy alone. “So we can conclude that 70 Gy in 7 weeks is comparable to 55.3 Gy in 17 consecutive days. That is, you can save some dose by shortening treatment time,” Dr. Dobrowsky said.

Both local tumor control and survival were significantly improved in patients treated with combined accelerated radiotherapy and mitomycin administration.

Local tumor control was 31% after standard radiation, 34% after accelerated radiation, and 48% following accelerated radiation administered concomitantly with mitomycin. Two-year survival was 27% with standard radiation, 28% with accelerated radiation, and 39% with accelerated radiation administered concomitantly with mitomycin.

All patients developed mucositis at the end of the second treatment week, with marked toxicity, especially in those patients treated with accelerated fractionation, with and without mitomycin, Dr. Dobrowsky reported, but the total duration of the mucositis did not differ among the three treatment groups.

Dr. Dobrowsky and his colleagues concluded that the addition of mitomycin to the accelerated radiation therapy regimen improved results significantly with regard to local tumor control and to actuarial overall survival. “From our results, we also conclude that hypoxia is a major factor for local failure, and this can, in part, be overcome by administration of mitomycin, which is more toxic to hypoxic cells,” he said.