Survival of patients in a Phase 1 Clinic: the M. D. Anderson Cancer Center experience

Cancer. 2009 Mar 1;115(5):1091-9. doi: 10.1002/cncr.24018.

Abstract

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 >or=440 x 10(9)/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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Child
  • Clinical Trials, Phase I as Topic / mortality*
  • Drug Delivery Systems
  • Female
  • Humans
  • Liver Neoplasms / secondary
  • Male
  • Middle Aged
  • Neoplasms / complications
  • Neoplasms / drug therapy*
  • Neoplasms / mortality*
  • Neoplasms / pathology
  • Prognosis
  • Retrospective Studies
  • Risk Assessment
  • Survival Analysis
  • Thrombocytosis / complications
  • Thromboembolism / complications
  • Treatment Outcome

Substances

  • Antineoplastic Agents