Oncology Research Today is a free monthly online journal that collates and summarizes the latest research about Oncology, including details on cancer, surgery, chemotherapy, radiotherapy.

Risks and benefits associated with novel phase 1 oncology trial designs.

Koyfman SA, Agrawal M, Garrett-Mayer E, Krohmal B, Wolf E, Emanuel EJ, Gross CP

Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH, USA.

BACKGROUND: Although aggressive dose escalation strategies were designed to improve the risk-benefit profile of phase 1 oncology trials, they have not been adequately studied. The prevalence of several novel trial designs and their association with a variety of clinical endpoints was evaluated. METHODS: A review of the literature was performed to identify phase 1 oncology studies of cytotoxic agents published from 2002 through 2004. RESULTS: Of 955 phase 1 oncology articles initially identified, 149 studies, comprising 4532 patients, were analyzed. Only 34% of studies utilized aggressive dose escalation schemes, 22% permitted intrapatient dose escalation, and only 28% enrolled fewer than 3 patients to any dose level. Studies that allowed intrapatient dose escalation or used fewer than 3 patients per dose were not associated with different rates of response or toxicity, nor did they increase the number of patients who received the recommended phase 2 dose. However, aggressive dose escalations were associated with increased rates of both hematologic (17% vs 10%) and nonhematologic (17% vs 13%) toxicity with similar response rates. Only studies that used conservative dose escalation designs and those that studied U.S. Food and Drug Administration (FDA)-approved agents required fewer patients to complete a trial. Trials of FDA-approved agents were also associated with higher response rates than trials of non-FDA-approved agents (10% vs 2%), without an increased risk of toxicity. CONCLUSIONS: Several novel aggressive design strategies intended to improve the risk-benefit profile of phase 1 oncology trials are not associated with improved clinical outcome, and may be harmful in certain instances.

Published 20 September 2007 in Cancer, 110(5): 1115-24.
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