The impact of concomitant medication use on patient eligibility for phase i cancer clinical trials

Abstract

Concomitant medication (CM) use may result in Phase I cancer clinical trial ineligibility due to concern for potential CM-investigational drug interactions or alteration of investigational drug absorption. Few studies have examined the impact of CM use on trial eligibility. Methods: We reviewed records of 274 patients on Phase I trials at a single academic institution. De-mographics, CM identities and classes, CM discontinuation, reasons, and incidence of CM substitution were recorded. CM-investigational drug cytochrome P450 (CYP) enzyme in-teractions were documented. Statistical analysis was performed using descriptive statistics. Results: 273 of 274 patients (99.6%, 95% confidence interval [CI] 98.9-100%) took CM, with a median of 8 CM per patient (range 0 - 42). CM discontinuation occurred in 67 cases (25%, 95% CI 19-30%). The most common CM classes discontinued were herbal (17 cases, 25%, 95% CI 16-37%) and proton pump inhibitors (15 cases, 22%, 95% CI 12-32%). CM discon-tinuation reasons were: protocol prohibition (32 cases, 48%, 95% CI 36-60%); potential CM-investigational drug interaction (25 cases, 37%, 95% CI 26-49%); other (10 cases, 15%, 95% CI 6-23%). A potential CM-investigational drug CYP interaction was noted in 122 cases (45%, 95% CI 39-50%). CM potentially weakly decreased investigational drug metabolism in 52 cases (43%, 95% CI 34-51%), and potentially strongly decreased investigational drug metab-olism in 17 cases (14%, 95% CI 8-20%). Investigational drug potentially weakly decreased CM metabolism in 39 cases (32%, 95% CI 24-40%), and potentially strongly decreased CM me-tabolism in 28 cases (23%, 95% CI 15-30%). CM substitution occurred in 36/67 cases (54%, 95% CI 41-66%) where CM were discontinued to allow for eventual participation in clinical trials. Overall in 2 cases (0.7%, 95% CI 0.1-2.6%), patients were protocol ineligible because CM could not be discontinued or substituted. Conclusions: This study highlights the high prevalence of concomitant medication use among cancer patients enrolled in phase I clinical trials. Most patients did meet trial eligibility criteria with careful substitution and discontin-uation of CM. The most common reason for discontinuation of CM was protocol prohibition. The most common medications discontinued were herbal, proton pump inhibitors, selective serotonin reuptake inhibitor anti-depressants, and non-steroidal anti-inflammatory drugs. © Ivyspring International Publisher.