Survival of patients in a Phase 1 clinic

BACKGROUND: Patients with advanced malignancies for whom standard therapy is ineffective may participate in phase 1 trials. To gain a better understanding of the clinical features that could influence benefit versus risk, the authors of this report assessed prognostic factors and survival for patients who were referred to a phase 1 clinic focused primarily on targeted agents. METHODS: The medical records of 200 sequential patients who presented to the Phase 1 Clinic at The University of Texas M. D. Anderson Cancer Center were reviewed, and their characteristics and survival were analyzed. RESULTS: The median patient age was 58 years (range, 12‐85 years), and 57% of patients were men. The median number of prior therapies was 4. Of 200 patients, 182 were treated on at least 1 phase 1 clinical trial. The median follow‐up of surviving patients was 21 months, and the median overall survival was 9 months (95% confidence interval [CI], 7.4‐10.8). In univariate analysis, the factors that predicted shorter survival were primary tumor in the gastrointestinal tract; a history of thrombosis, liver metastases, and elevated levels of serum lactate dehydrogenase; platelet count; carbohydrate antigen 9 (Ca19‐9) and Ca‐125 levels; aspartate aminotransferase levels, and alkaline phosphatase levels (P < .05 for each). In multivariate analysis, independent factors that predicted shorter survival were a history of thromboembolism (hazard ratio [HR], 2.38; 95% CI, 1.29‐4.39; P = .005), platelets ≥440 × 109/L (HR, 1.72; 95% CI, 1.12‐2.65; P = .014), and the presence of liver metastases (HR, 1.51; 95% CI, 1.09‐2.09; P = .013). CONCLUSIONS: Patients who were referred to phase 1 studies had a short median survival (9 months). Patients with thrombocytosis, liver metastases, and a history of thromboembolism had worse outcomes. A prognostic score is proposed. Cancer 2009. © 2009 American Cancer Society. In this analysis of patients who were seen in the Phase 1 Clinic at The University of Texas M. D. Anderson Cancer Center, overall survival and risk factors that were predictive of survival were identified. In multivariate analysis, independent factors that predicted shorter survival were a history of thromboembolism, a platelet count ≥440 × 109/L, and the presence of liver metastases. These factors can be used to identify specific risk groups, to compare results among different phase 1 clinical trials, and to improve patient selection for these trials.