title: A phase I/II study of a hypoxic cell radiosensitizer KU-2285 in combination with intraoperative radiotherapy.
abstract: 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.
authors.affiliation: Department of Radiology, Faculty of Medicine, Kyoto University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Shibamoto
authors.forename: G
authors.initials: G
authors.lastname: Ohshio
authors.forename: R
authors.initials: R
authors.lastname: Hosotani
authors.forename: Y
authors.initials: Y
authors.lastname: Nishimura
authors.forename: T
authors.initials: T
authors.lastname: Manabe
authors.forename: M
authors.initials: M
authors.lastname: Imamura
authors.forename: M
authors.initials: M
authors.lastname: Abe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000532:radiotherapy* / Q000601:surgery*; D002648:Child; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007430:Intraoperative Care; D008297:Male; D008875:Middle Aged; D009593:Nitroimidazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012516:Osteosarcoma / Q000532:radiotherapy* / Q000601:surgery*; D010190:Pancreatic Neoplasms / Q000532:radiotherapy* / Q000601:surgery*; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C069296:KU 2285