The Cancer Research UK experience of pre-clinical toxicology studies to support early clinical trials with novel cancer therapies

Eur J Cancer. 2004 Apr;40(6):899-906. doi: 10.1016/j.ejca.2003.12.020.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Clinical Trials, Phase I as Topic*
  • Female
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Mice
  • Neoplasms / drug therapy*
  • Rats

Substances

  • Antineoplastic Agents