Prognostic factors of metastatic renal cell carcinoma after failure of immunotherapy: new paradigm from a large phase III trial with shark cartilage extract AE 941

J Urol. 2007 Nov;178(5):1901-5. doi: 10.1016/j.juro.2007.07.035. Epub 2007 Sep 17.

Abstract

Purpose: We analyzed prognostic factors, described survival and generated a prognostic model in patients with metastatic renal cell carcinoma in whom immunotherapy failed and who were potentially eligible for novel agents.

Materials and methods: An analysis of the relationship between clinical features and survival was performed in 300 patients with advanced renal cell carcinoma in whom immunotherapy had failed and who were subsequently treated as part of a single, phase III clinical trial with the anti-angiogenic agent Neovastat (shark cartilage extract AE 941). Clinical features were first examined univariately and a stepwise modeling approach based on Cox proportional hazard regression was then performed to generate a multivariate model.

Results: Median and progression-free survival (prognostic factors) for the whole cohort was 12.6 and 2 months, respectively. Prognostic features associated with shorter survival on multivariate analysis were the number of metastatic sites (greater than 1), time from nephrectomy to metastatic disease (less than 2 years), high alkaline phosphatase, abnormal corrected serum Ca and high lactate dehydrogenase (greater than 1.5 x the upper limit of normal). Four prognostic subgroups were identified by counting the number of adverse prognostic factors. Median survival in patients with zero adverse prognostic factors was 15.6 months compared to 11.7 months in patients with 1, 8.5 months in patients with 2 and 3.5 months in patients with 3 or more.

Conclusions: We identified 4 risk groups to predict survival in previously treated patients with renal cell carcinoma. This model was based on data from what is to our knowledge the largest experience in this population. It should be used in clinical trial design, risk stratification and patient counseling.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alberta / epidemiology
  • Biopsy
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / secondary
  • Carcinoma, Renal Cell / therapy*
  • Cartilage
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • France / epidemiology
  • Humans
  • Immunotherapy / methods*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / therapy*
  • Male
  • Middle Aged
  • Ohio / epidemiology
  • Poland / epidemiology
  • Prognosis
  • Proportional Hazards Models
  • Quebec / epidemiology
  • Retrospective Studies
  • Risk Factors
  • Survival Rate
  • Tissue Extracts / therapeutic use*
  • Treatment Failure

Substances

  • Tissue Extracts
  • shark cartilage extract