A PHASE I II STUDY OF A HYPOXIC CELL RADIOSENSITIZER KU-2285 IN COMBINATION WITH INTRAOPERATIVE RADIOTHERAPY/

A fluorinated 2-nitroimidazole radiosensitizer KU-2285 was given befor e 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 dos e of KU-2285 administered ranged from 1 to 9 g m(-2). Four patients re ceived a dose of 9 g m(-2), and ten received 6.8-7 g m(-2). All patien ts tolerated KU-2285 well, and no drug-related toxicity was observed. The average tumour concentration of KU-2285 immediately after IORT was 166 mu g g(-1) at dose of 6.8-7 g m(-2) and 333 mu g g(-1) at 9 g m(- 2). The average tumour-plasma ratio was greater than or equal to 0.82. Eleven patients with unresectable but localized pancreatic cancer tre ated with KU-2285 plus IORT and external beam radiotherapy had a media n survival time of 11 months and 1-year local control rate of 50%, whi ch compares favourably with those of 8 months (P = 0.26) and 28% (P = 0.10) for 22 matched historical control patients. The five patients wi th osteosarcoma attained local control. The results of this first stud y on KU-2285 and IORT appear encouraging, and further studies of this compound seem to be warranted.