Journal
JOURNAL OF CLINICAL ONCOLOGY
Volume 30, Issue 9, Pages 996-1004Publisher
AMER SOC CLINICAL ONCOLOGY
DOI: 10.1200/JCO.2010.34.5074
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Funding
- Drug Development Unit of the Royal Marsden National Health Service (NHS) Foundation
- Institute of Cancer Research
- European Drug Development Network (EDDN) centres
- Cancer Research UK
- Experimental Cancer Medicine Centre [110722]
- National Institute of Health Research Biomedical Research Centre [CA51/A7401]
- Departments of Health
- ASCO Cancer Foundation
- ESMO Foundation
- Cancer Research UK [11650] Funding Source: researchfish
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Purpose The appropriate selection of patients for early clinical trials presents a major challenge. Previous analyses focusing on this problem were limited by small size and by interpractice heterogeneity. This study aims to define prognostic factors to guide risk-benefit assessments by using a large patient database from multiple phase I trials. Patients and Methods Data were collected from 2,182 eligible patients treated in phase I trials between 2005 and 2007 in 14 European institutions. We derived and validated independent prognostic factors for 90-day mortality by using multivariate logistic regression analysis. Results The 90-day mortality was 16.5% with a drug-related death rate of 0.4%. Trial discontinuation within 3 weeks occurred in 14% of patients primarily because of disease progression. Eight different prognostic variables for 90-day mortality were validated: performance status (PS), albumin, lactate dehydrogenase, alkaline phosphatase, number of metastatic sites, clinical tumor growth rate, lymphocytes, and WBC. Two different models of prognostic scores for 90-day mortality were generated by using these factors, including or excluding PS; both achieved specificities of more than 85% and sensitivities of approximately 50% when using a score cutoff of 5 or higher. These models were not superior to the previously published Royal Marsden Hospital score in their ability to predict 90-day mortality. Conclusion Patient selection using any of these prognostic scores will reduce non-drug-related 90-day mortality among patients enrolled in phase I trials by 50%. However, this can be achieved only by an overall reduction in recruitment to phase I studies of 20%, more than half of whom would in fact have survived beyond 90 days. J Clin Oncol 30: 996-1004. (C) 2012 by American Society of Clinical Oncology
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