Barriers in phase I cancer clinical trials referrals and enrollment: five-year experience at the Princess Margaret Hospital

A retrospective chart review was performed for all new patients referred and seen in the phase I clinic at the Princess Margaret Hospital between January 2000 and June 2005. Data on their demographics, medical history, and details of trial participation or non-entry were recorded.A total of 667 new phase I referrals were seen during the stated period. Of these patients, 197 (29.5%) patients were enrolled into a phase I trial, and 64.5% of them started trial within 1 month of the initial visit. About a quarter (165 of 667) of the patients referred were deemed ineligible at their first visit, with the most frequent reasons for ineligibility being poor performance status, unacceptable bloodwork, too many prior treatments and rapid disease progression. The remaining 305 patients (45.7%) were potentially eligible at their initial visit, but never entered a phase I trial. The main reasons for their non-entry were patient refusal, other treatment recommended first, and lack of available trials or trial spots.This study provides information on the clinical realities underlying a referral to a phase I clinic and eventual trial enrollment. Better selection of patients, appropriate education of referring physicians, and opening phase I trials with fewer restrictions on some criteria such as prior therapy may enhance their recruitment rates.Phase I clinical trials evaluate the dosing and toxicities of novel agents or combinations of agents in humans after appropriate preclinical testing of safety, toxicology and pharmacology. Oncology patients who have been referred to the phase I trials clinic represent the unique subset of patients who have exhausted standard treatment options, yet continue to be functionally well. Because the risks associated with an investigational drug are unknown, and the likelihood of therapeutic response is relatively small [1], multiple studies have examined the motivations of these patients for participating in phase I oncology trials. While patients