Patient selection for oncology phase I trials: A multi-institutional study of prognostic factors

David Olmos, Roger P. A'Hern, Silvia Marsoni, Rafael Morales, Carlos Gomez-Roca, Jaap Verweij, Emile E. Voest, Patrick Schof̈fski, Joo Ern Ang, Nicolas Penel, Jan H. Schellens, Gianluca Del Conte, Andre T. Brunetto, T. R Jeffry Evans, Richard Wilson, Elisa Gallerani, Ruth Plummer, Josep Tabernero, Jean Charles Soria, Stan B. Kaye

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)996-1004
Number of pages9
JournalJournal of Clinical Oncology
Issue number9
Publication statusPublished - Mar 20 2012

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)


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