Shibamoto Y, Ohshio G, Hosotani R, Nishimura Y, Manabe T, Imamura M, Abe M
Department of Radiology, Faculty of Medicine, Kyoto University, Japan.
Br J Cancer. 1997;76(11):1474-9. doi: 10.1038/bjc.1997.580.
A fluorinated 2-nitroimidazole radiosensitizer KU-2285 was given before intraoperative radiotherapy (IORT) to 30 patients with unresectable, unresected or macroscopic residual tumours. Twenty-three patients had pancreatic cancer and five had osteosarcoma. The IORT dose was 30 Gy for unresectable pancreatic cancer and 60 Gy for osteosarcoma. The dose of KU-2285 administered ranged from 1 to 9 g m-2. Four patients received a dose of 9 g m-2, and ten received 6.8-7 g m-2. All patients tolerated KU-2285 well, and no drug-related toxicity was observed. The average tumour concentration of KU-2285 immediately after IORT was 166 microg g-1 at dose of 6.8-7 g m-2 and 333 microg g-1 at 9 g m-2. The average tumour-plasma ratio was > or = 0.82. Eleven patients with unresectable but localized pancreatic cancer treated with KU-2285 plus IORT and external beam radiotherapy had a median survival time of 11 months and 1-year local control rate of 50%, which compares favourably with those of 8 months (P = 0.26) and 28% (P = 0.10) for 22 matched historical control patients. The five patients with osteosarcoma attained local control. The results of this first study on KU-2285 and IORT appear encouraging, and further studies of this compound seem to be warranted.
在术中放疗（IORT）前，对30例患有无法切除、未切除或有肉眼可见残留肿瘤的患者给予氟化2-硝基咪唑放射增敏剂KU-2285。23例患者患有胰腺癌，5例患有骨肉瘤。对于无法切除的胰腺癌，IORT剂量为30 Gy，对于骨肉瘤为60 Gy。KU-2285的给药剂量范围为1至9 g m-2。4例患者接受了9 g m-2的剂量，10例接受了6.8 - 7 g m-2的剂量。所有患者对KU-2285耐受性良好，未观察到与药物相关的毒性。IORT后立即测得的KU-2285平均肿瘤浓度，在剂量为6.8 - 7 g m-2时为166 μg g-1，在9 g m-2时为333 μg g-1。平均肿瘤与血浆比值≥0.82。11例接受KU-2285加IORT及外照射放疗的无法切除但局限的胰腺癌患者，中位生存时间为11个月，1年局部控制率为50%，与22例匹配的历史对照患者的8个月（P = 0.26）和28%（P = 0.10）相比更具优势。5例骨肉瘤患者实现了局部控制。这项关于KU-2285与IORT的首次研究结果似乎令人鼓舞，对该化合物的进一步研究似乎是有必要的。
