A phase I/II study of a hypoxic cell radiosensitizer KU-2285 in combination with intraoperative radiotherapy.
A phase I/II study of a hypoxic cell radiosensitizer KU-2285 in combination with intraoperative radiotherapy.
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DOI：
10.1038/bjc.1997.580
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发表时间：
1997
影响因子：
8.8
通讯作者：
Abe, M
中科院分区：
文献类型：
--
作者：
Shibamoto, Y;Ohshio, G;Hosotani, R;Nishimura, Y;Manabe, T;Imamura, M;Abe, M
氟化2-硝基咪唑放射增敏剂KU-2285术前放疗（IORT）30例患者不可切除，未切除或肉眼可见的残留肿瘤。23名患者患有胰腺癌，5名患有骨肉瘤。对于不能切除的胰腺癌，IORT剂量为30戈伊，对于骨肉瘤，IORT剂量为60戈伊。KU-2285的给药剂量范围为1 - 9 g m-2。4名患者接受了9 g m-2的剂量，10名患者接受了6.8-7 g m-2的剂量。所有患者对KU-2285耐受良好，未观察到药物相关毒性。IORT后即刻KU-2285的平均肿瘤浓度在6.8-7 g m-2剂量下为166 microg g g-1，在9 g m-2剂量下为333 microg g g-1。平均肿瘤-血浆比率>或= 0.82。KU-2285联合IORT和外照射治疗的11例不可切除但局限性胰腺癌患者的中位生存时间为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，这一结果更为有利。5例骨肉瘤患者均获得局部控制。对KU-2285和IORT的首次研究结果似乎令人鼓舞，对这种化合物的进一步研究似乎是必要的。
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.