The outcome of patients treated with sunitinib prior to planned nephrectomy in metastatic clear cell renal cancer

Eur Urol. 2011 Sep;60(3):448-54. doi: 10.1016/j.eururo.2011.05.028. Epub 2011 May 17.

Abstract

Background: The role of cytoreductive nephrectomy in metastatic clear cell renal cell carcinoma (ccRCC) is controversial.

Objective: To determine the outcome of patients with metastatic ccRCC who receive sunitinib prior to planned nephrectomy.

Design, setting, and participants: The study combined the data from two prospective phase 2 studies that assessed upfront sunitinib (12-16 wk) prior to nephrectomy in previously untreated patients with metastatic renal cell carcinoma (RCC). Sunitinib was discontinued during the perioperative period (median: 29 d).

Intervention: Sunitinib 50mg in six weekly cycles (4 wk on, 2 wk off).

Measurements: Progression-free (PFS) and overall survival (OS) using the Kaplan-Meier method.

Results and limitations: Twenty-one patients (32%) had Memorial Sloan-Kettering Cancer Centre (MSKCC) poor-risk disease; 45 (68%) had intermediate-risk disease. Nephrectomy was not performed in 19 (29%), most commonly due to disease progression (n = 12). The PFS for the cohort was 6.3 mo (95% confidence interval [CI], 5.1-8.5). Seventeen (36%) patients progressed during the treatment break, 13 (76%) of whom stabilised upon reinitiating of sunitinib. The OS for the cohort was 15.2 mo (95% CI, 10.3-NA). The OS for the intermediate MSKCC risk group was significantly longer than that for the poor-risk group (26.0 mo [95% CI, 13.6-NA] and 9.0 mo [95% CI, 5.8-20.5], respectively; p < 0.01). In multivariate analysis, progression of disease prior to planned nephrectomy (hazard ratio [HR]: 5.34; 95% CI, 3.17-13.27), high Fuhrman grade (HR 3.27; 95% CI, 1.38-7.72), and MSKCC poor risk at diagnosis (HR 4.75; 95% CI, 2.05-11.02) were associated with short survival (p < 0.01). However, in the absence of randomised studies it is not possible to determine if this approach is beneficial.

Conclusions: Upfront sunitinib prior to planned nephrectomy in intermediate-risk disease is associated with a median survival of >2 yr despite frequent progression during treatment break. Progression in metastatic sites prior to planned surgery and MSKCC poor-risk disease was associated with a poor outcome.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / secondary
  • Carcinoma, Renal Cell / surgery*
  • Chemotherapy, Adjuvant
  • Clinical Trials, Phase II as Topic
  • Disease Progression
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Humans
  • Indoles / administration & dosage*
  • Indoles / adverse effects
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / surgery*
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Nephrectomy* / adverse effects
  • Nephrectomy* / mortality
  • Patient Selection
  • Proportional Hazards Models
  • Prospective Studies
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects
  • Pyrroles / administration & dosage*
  • Pyrroles / adverse effects
  • Risk Assessment
  • Risk Factors
  • Sunitinib
  • Survival Rate
  • Time Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Indoles
  • Protein Kinase Inhibitors
  • Pyrroles
  • Sunitinib