Predictors for early trial discontinuation of patients with cancer participating in phase I clinical trials

Abstract Background Patients with cancer who are refractory to standard treatments may participate in phase I clinical trials. Despite stringent eligibility criteria for trial participation, early discontinuation often occurs. These patients do not benefit from study treatment and may experience additional burden from participation, while adequate evaluation of novel treatment strategies is hampered. The aim of this study was to identify predictors for early discontinuation of phase I clinical trials. Methods Data from patients with solid tumors who participated in phase I trials in our center were pooled for the current analysis. Early trial discontinuation was defined as (i) trial discontinuation within 28 days after administration of the first dose of the investigated drug or (ii) discontinuation before administration of the first dose in patients who were found to be eligible. Based on the literature, the following potential predictors were examined: opioid use, number of metastatic sites, body mass index, ECOG/WHO performance status, comorbidity history of thromboembolism, hemoglobin level, platelet count, leukocytes, lymphocytes, absolute neutrophil count, serum sodium level, creatinine clearance, serum albumin level, serum alkaline phosphatase level, serum aspartate aminotransferase level (AST), serum lactate dehydrogenase level and. Multilevel logistic regression analyses were conducted and Odds ratio (OR) and 95% confidence interval (95%CI) were reported. Results Data from 154 patients recruited in 8 phase I clinical trials were analyzed. Thirty-six (23%) participants discontinued the trial early. Baseline hyponatremia (OR = 3.69, 95%CI=1.09-12.47) and an elevated AST level (OR = 2.57, 95%CI=1.10-6.01) were independent predictors for early trial discontinuation. Conclusions Hyponatremia and an elevated serum AST level were identified as significant independent predictors for early trial discontinuation in patients with cancer participating in phase I clinical trials. These predictors will be further investigated in a prospective study, to determine their added value in minimizing early trial discontinuation of patients participating in phase I oncology trials. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.