Intrinsic resistance to tyrosine kinase inhibitors is associated with poor clinical outcome in metastatic renal cell carcinoma

BMC Cancer. 2011 Jul 14:11:295. doi: 10.1186/1471-2407-11-295.

Abstract

Background: Data on sequential therapy in patients with metastatic renal cell carcinoma (mRCC) and intrinsic resistance to receptor tyrosine kinase inhibitor (rTKI) treatment remains vague.

Methods: We retrospectively studied treatment characteristics and outcome of mRCC patients refractory to first rTKI therapy.

Results: Thirty-five mRCC patients (male, 18; female, 11) with primary resistance to first rTKI therapy (sunitinib, n = 28; sorafenib, n = 7) and a median treatment interval of 2.4 months (1 - 4.6) were identified. In 22 patients, progressive disease (PD) was determined by a new metastatic lesion. Of these, 16 patients received subsequent therapy with 12 patients remaining refractory and 4 patients achieving disease stabilization. In 13 patients continuous growth of existing metastatic lesions determined PD. Of these, 9 received sequential therapy with 6 achieving disease stabilization. Altogether, 25 patients were treated sequentially (rTKI: n = 15; mTOR-inhibitor: n = 10) and achieved a median PFS of 3.2 months (range, 1-16.6). Fifteen patients failed to respond to either line of therapy. Disease control was not associated with type of subsequent therapy. Median OS was 14.9 months (CI: 5.5-24.4).

Conclusion: Intrinsic resistance to rTKI is associated with a low chance of response to sequential therapy and a poor prognosis in mRCC patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Benzenesulfonates / therapeutic use
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Indoles / therapeutic use
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Niacinamide / analogs & derivatives
  • Phenylurea Compounds
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyridines / therapeutic use
  • Pyrroles / therapeutic use
  • Retrospective Studies
  • Sorafenib
  • Sunitinib
  • Time Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Benzenesulfonates
  • Indoles
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Pyridines
  • Pyrroles
  • Niacinamide
  • Sorafenib
  • Sunitinib