Originally published as JCO Early Release 10.1200/JCO.2008.19.5081 on March 30 2009

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

Hendrik-Tobias Arkenau, Jorge Barriuso, David Olmos, Joo Ern Ang, Johann de Bono, Ian Judson, Stan Kaye

From the Royal Marsden Hospital and Institute of Cancer Research, Sutton, United Kingdom.

Corresponding author: Stan Kaye, MD, Royal Marsden Hospital and Institute of Cancer Research, Drug Development Unit, Downs Rd, SM2 5PT, Sutton, United Kingdom; e-mail: stan.kaye{at}rmh.nhs.uk.

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 selection for phase I trial entry.

H.T.A. and J.B. contributed equally to this work.

Support to the Drug Development Unit provided by Cancer Research UK and the Department of Health through a Programme Grant, an Experimental Cancer Medicine Centre grant (Grant No. C51/A7401), and as part of the National Institute for Health Research Biomedical Research Centre at the Royal Marsden Hospital. H.-T.A. was recipient of an American Society of Clinical Oncology merit award for the oral presentation at the 44th Annual Meeting of the American Society of Clinical Oncology (2008). J.B. is supported by the Fondo de Investigación Sanitaria Grant No. CM05/00,143 and Fundación para la Investigación Biomédica Hospital La Paz. D.O. was a recipient of the European Society of Medical Oncology fellowship 2006 to 2007.

Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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