Predictive factors for response to treatment in patients with advanced renal cell carcinoma

Invest New Drugs. 2012 Dec;30(6):2443-9. doi: 10.1007/s10637-012-9836-4. Epub 2012 May 27.

Abstract

Introduction: The analysis of predictive factors of response may aid in predicting which patients with advanced renal cell carcinoma (RCC) would be good candidates for systemic treatments.

Materials and methods: The expression of several biomarkers was retrospectively analyzed using immunohistochemistry (IHC), as well as 2 analytical variables in 135 patients with advanced RCC treated with cytokines (CK) and/or new targeted drugs (NTD).

Results: 67 patients were treated solely with NTD and 68 with CK (23 also received NTD). Univariate analysis: HIF1α did not correlate significantly with response to these drugs. Overexpression of CAIX was associated with more responses (%) to NTD (64.7 vs. 21.1; p = 0.004) and CK (22.6 vs. 0; p = 0.038). PTEN demonstrated predictive value of response to sunitinib (70.8 vs. 34.1; p = 0.005). p21 was associated with a lower response to sunitinib (35.9 vs. 65.4; p = 0.025). Thrombocytosis was not significantly associated with response to NTD, although it was with CK (0 vs. 20; p = 0.017). Neutrophilia correlated with a lower response to NTD (29.6 vs. 57.5; p = 0.045), although not with CK. Multivariate analysis: Overexpression of CAIX was an independent predictor of significantly higher response to NTD and CK; OR = 8.773 (p < 0.001).

Conclusions: Our findings highlight the usefulness of CAIX in selecting patients with advanced RCC as candidates for systemic treatment. PTEN and p21 may be important in predicting response to sunitinib. Thrombocytosis and neutrophilia correlate well with response to CK and NTD, respectively.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / metabolism
  • Antineoplastic Agents / therapeutic use*
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / metabolism
  • Carcinoma, Renal Cell / diagnosis
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cytokines / therapeutic use*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Kidney Neoplasms / diagnosis
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / metabolism*
  • Leukocyte Disorders / diagnosis
  • Middle Aged
  • PTEN Phosphohydrolase / metabolism
  • Prognosis
  • Thrombocytosis / diagnosis

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cytokines
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases