title: The Cancer Research UK experience of pre-clinical toxicology studies to support early clinical trials with novel cancer therapies.
abstract: 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.
authors.affiliation: Drug Development Office, Cancer Research UK, PO Box 123, WC2A 3PX London, UK.
authors.forename: D R
authors.initials: DR
authors.lastname: Newell
authors.forename: J
authors.initials: J
authors.lastname: Silvester
authors.forename: C
authors.initials: C
authors.lastname: McDowell
authors.forename: S S
authors.initials: SS
authors.lastname: Burtles
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents