A phase II study of presurgical sunitinib in patients with metastatic clear-cell renal carcinoma and the primary tumor in situ

Urology. 2011 Oct;78(4):832-7. doi: 10.1016/j.urology.2011.05.034. Epub 2011 Jul 29.

Abstract

Objective: To investigate response rate (RR) of the primary tumor after presurgical sunitinib before planned cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC). Secondary endpoints were safety and if this strategy can be used to identify patients who progress rapidly and may not benefit from CN.

Methods: Prospective study to detect a 25% response evaluation criteria in solid tumors RR (RECIST-RR) in the primary tumor (Simon two-stage design). CN was performed after 2 cycles of sunitinib 50 mg/d. Response in the primary tumor and metastatic sites, change of longest diameter of the primary tumor (Δ-LDT), progression-free survival (PFS), and adverse events were assessed.

Results: Twenty-two patients with primary mRCC were included. The trial did not enter the second stage because only 1 primary tumor responded partially in the first stage (4.5%). Median Δ-LDT was -9.5% (range 2.2 to -36%). A >10% Δ-LDT was significantly associated with a high probability to survive 2 years (P = .01). At metastatic sites, 7 patients developed a partial response (31.8%), 7 stable disease (31.8%), and 8 progressive disease (36.4%). Subsequently 3 (13.6%) developed a complete response after CN and continued taking sunitinib. Median PFS is 7 months (range 0-41). Median follow-up is 23 months (range 2-41). Median overall survival has not been reached.

Conclusions: Downsizing of primary tumors after 2 cycles of sunitinib is modest but associated with long-term survival. Patients with progression of metastases after pretreatment have short survival and are unlikely to benefit from CN.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / surgery*
  • Combined Modality Therapy
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Humans
  • Indoles / therapeutic use*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / surgery*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Probability
  • Prospective Studies
  • Pyrroles / therapeutic use*
  • Sunitinib
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Indoles
  • Pyrroles
  • Sunitinib

Supplementary concepts

  • Clear-cell metastatic renal cell carcinoma