Cytokines and angiogenic factors in patients with metastatic renal cell carcinoma treated with interferon-alpha: association of pretreatment serum levels with survival

Ann Oncol. 2009 Oct;20(10):1682-7. doi: 10.1093/annonc/mdp054. Epub 2009 Jun 18.

Abstract

Background: To correlate serum cytokine and angiogenic factor (CAF) levels with overall survival (OS) in metastatic renal cell carcinoma (mRCC) treated with interferon-alpha (IFN-alpha).

Patients and methods: Serum CAF levels were measured in 103 patients treated on a randomized trial with IFN-alpha 0.5 million units (MU) twice daily or 5 MU daily. Concentrations of 17 analytes were determined by multiplex bead immunoassays [vascular endothelial growth factor A (VEGF(A)) and several cytokines] or enzyme-linked immunosorbent assay (basic fibroblast growth factor). We used proportional hazards models to evaluate the effect of CAF levels and clinical factors on OS.

Results: Pretreatment serum interleukin (IL) 5, IL-12 p40, VEGF(A), and IL-6 levels and Memorial Sloan-Kettering Cancer Center risk grouping independently correlated with OS, with hazard ratios of 2.33, 2.00, 2.07, 1.82, and 0.39, respectively (concordance index = 0.69 for the combined model versus 0.60 for the CAF model versus 0.52 for the clinical model). Based on an index derived from these five risk factors (RFs), patients with 0-2 RF had a median OS time of 32 months versus 9 months for patients with 3-5 RF (P < 0.0001).

Conclusions: Serum CAF profiling contributes to prognostic evaluation in mRCC and helps to identify a subset of patients with 20% 5-year OS.

MeSH terms

  • Angiogenesis Inducing Agents / blood
  • Angiogenesis Inducing Agents / therapeutic use*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / secondary*
  • Chi-Square Distribution
  • Cytokines / blood
  • Cytokines / therapeutic use*
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fibroblast Growth Factor 2 / blood
  • Follow-Up Studies
  • Humans
  • Immunoassay
  • Interferon-alpha / therapeutic use*
  • Interleukin-12 Subunit p40 / blood
  • Interleukin-12 Subunit p40 / therapeutic use
  • Interleukin-5 / blood
  • Interleukin-5 / therapeutic use
  • Interleukin-6 / blood
  • Interleukin-6 / therapeutic use
  • Kaplan-Meier Estimate
  • Male
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Survival Analysis
  • Time Factors
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor A / therapeutic use

Substances

  • Angiogenesis Inducing Agents
  • Cytokines
  • Interferon-alpha
  • Interleukin-12 Subunit p40
  • Interleukin-5
  • Interleukin-6
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2