Fulton D S, Urtasun R C, Shin K H, Geggie P H, Thomas H, Muller P J, Moody J, Tanasichuk H, Mielke B, Johnson E
Int J Radiat Oncol Biol Phys. 1984 Sep;10(9):1709-12. doi: 10.1016/0360-3016(84)90533-9.
Multiple daily fractionated radiation therapy (MDF) may be more effective than conventionally fractionated radiation therapy (CF) in the treatment of malignant glioma. The hypoxic cell sensitizer misonidazole (MISO) could be more effective when employed with small fractions of radiation every 4 hours to take advantage of the long half-life of the drug. To evaluate MDF and MDF in combination with MISO, a randomized prospective trial was initiated. Between January 1981, and December 1982, patients with histologically verified astrocytoma with anaplastic foci or glioblastoma multiforme were randomized to CF (5800 cGy, 30 fractions, 6 weeks), MDF (6141 cGy, 69 fractions, 4 1/2 weeks, at 89 cGy every 4 hours 3 times daily) and MDF in combination with MISO (1.25 gm/M2 three times weekly for the first 3 weeks). In January 1983, the CF arm was dropped and a high dose MDF arm added (7120 cGy, 80 fractions, 5 1/2 weeks, at 89 cGy per fraction every 4 hours 3 times daily). CCNU chemotherapy was given at the time of tumor progression. One hundred and twenty-eight patients were evaluated (38 CF, 42 MDF, 37 MDF plus MISO, and 11 high dose MDF). Median survival was 29 weeks for CF, 45 weeks for MDF and 50 weeks for MDF plus MISO. Survival was significantly improved for patients treated with MDF compared to patients treated with CF (p less than .002). The addition of MISO to MDF did not result in further improvement in survival. Acute toxicity was acceptable. No clinically apparent delayed toxicity was observed.
在恶性胶质瘤的治疗中，每日多次分割放射治疗（MDF）可能比传统分割放射治疗（CF）更有效。缺氧细胞增敏剂米索硝唑（MISO）与每4小时小剂量放射治疗联合使用时可能更有效，因为该药半衰期长。为了评估MDF以及MDF与MISO联合使用的效果，开展了一项随机前瞻性试验。1981年1月至1982年12月期间，组织学确诊为间变灶星形细胞瘤或多形性胶质母细胞瘤的患者被随机分为CF组（5800 cGy，30次分割，6周）、MDF组（6141 cGy，69次分割，4.5周，每4小时89 cGy，每日3次）和MDF联合MISO组（前3周每周3次，1.25 gm/M2）。1983年1月，取消CF组，增加高剂量MDF组（7120 cGy，80次分割，5.5周，每4小时每次分割89 cGy，每日3次）。肿瘤进展时给予洛莫司汀化疗。共评估了128例患者（38例CF组、42例MDF组、37例MDF加MISO组和11例高剂量MDF组）。CF组的中位生存期为29周，MDF组为45周，MDF加MISO组为50周。与CF组患者相比，MDF组患者的生存期显著改善（p<0.002）。MDF联合MISO未使生存期进一步改善。急性毒性可接受。未观察到明显的临床延迟毒性。
