The Cancer Research UK experience of pre-clinical toxicology studies to support early clinical trials with novel cancer therapies.
Pre-clinical toxicology studies in rodents and Phase I clinical trial data are summarised for 14 novel anticancer therapies. With only one exception, an antifolate antimetabolite, rodent toxicology predicted a safe Phase I trial starting dose and the majority of the dose limiting toxicities, in particular haematological toxicity. For targeted agents with well-defined pharmacodynamic markers, illustrated in the current study by 3 anti-endocrine drugs and one resistance modifier, the definition of a maximum tolerated dose can be avoided. Together with earlier data, the current study confirms that pre-clinical toxicology studies in a non-rodent species are not routinely needed for the safe conduct of early clinical trials with new cancer chemotherapies.
Newell
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Drug Development Office, Cancer Research UK, PO Box 123, WC2A 3PX London, UK.
Silvester
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J
McDowell
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Burtles
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D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017321:Clinical Trials, Phase I as Topic; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D051381:Rats
D000970:Antineoplastic Agents