A toxicity and pharmacokinetic study in man of the hypoxic-cell radiosensitiser RSU-1069

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Abstract
RSU-1069 is the principal member of a new group of hypoxiccell radio- and chemo- (“mixed function”) sensitisers. They contain both a 2-nitroimidazole ring similar to that of misonidazole and an aziridine ring which may function to bind the molecule to DNA (Adams et al, 1984; Walling et al, 1986). The compound was selected for clinical evaluation because of the high sensitiser enhancement ratio (SER) achieved following radiotherapy of hypoxic cells in vitro and in animal tumour studies (Adams et al, 1984); at 0.2 mM RSU-1069 the SER was 2.0 (cf 0.2 mM misonidazole, SER ≤ 1.6) and the concentration of RSU-1069 required to achieve an SER of 1.6 (C1.6) was 7.5 × 10−5M to 1 × 10−4M (cf misonidazole C1.6 = 3 × 10−4M) (Adams et al, 1984; Ahmed et al, 1986). A toxicity study has been performed to define the tolerated single dose in man, and the plasma pharmacokinetics of RSU-1069 have been analysed in three patients treated at the high end of the dose range studied.