Prospective Validation of a Prognostic Score to Improve Patient Selection for Oncology Phase I Trials

作者：Hendrik‐Tobias Arkenau, Jorge Barriuso, David Olmos, Joo Ern Ang, Johann Sebastian De Bono, Ian Robert Judson, Stan B. Kaye · 发表于：Journal of Clinical Oncology · 年份：2009 · DOI：10.1200/jco.2008.19.5081 · 被引用次数：212 · 研究领域：Statistical Methods in Clinical Trials、Cancer Treatment and Pharmacology、Prostate Cancer Diagnosis and Treatment

PURPOSE: With the aim of improving patient selection for phase I trials, we previously performed a retrospective analysis of 212 phase I oncology patients where we were able to develop a prognostic score predicting overall survival (OS). This prospective study was performed to test the validity of the prognostic score. PATIENTS AND METHODS: On the basis of our retrospective multivariate analysis, three factors were associated with poor survival (albumin < 35 g/L, lactate dehydrogenase [LDH] > upper limit of normal [ULN], and > two sites of metastases). We integrated these into a prognostic score ranging from 0 to 3 and analyzed this score in a prospectively selected cohort of 78 patients enrolled onto phase I trials. RESULTS: All patients had progressive disease before study entry. The median age was 56 years (range, 18 to 79 years). After a median follow-up time of 27.3 weeks, patients with a prognostic score of 0 to 1 (n = 43) had superior OS (33.0 weeks; 95% CI, 24 to 42 weeks) compared with patients with a score of 2 to 3 (n = 35; 15.7 weeks; 95% CI, 11 to 21 weeks). Our multivariate analysis confirmed that our prognostic score was an independent marker for OS, with a hazard ratio of 1.4 (95% CI, 1.02 to 1.9; P = .036). CONCLUSION: This is the first prospective analysis confirming that a prognostic score based on objective markers, including albumin less than 35 g/L, LDH more than ULN, and more than two sites of metastasis, is a helpful tool in the process of patient sele...