Combined immunotherapy with low-dose IL-2 plus IFN-alpha for metastatic renal cell carcinoma: survival benefit for selected patients with lung metastasis and serum sodium level

Jpn J Clin Oncol. 2011 Aug;41(8):1023-30. doi: 10.1093/jjco/hyr067. Epub 2011 Jun 4.

Abstract

Objective: To clarify the survival benefit of immunotherapy for renal cell carcinoma patients with lung metastasis using low-dose interleukin-2 plus interferon-α, we examined survival outcomes and factors associated with prognosis.

Methods: This was a multicenter prospective study. Nephrectomized renal cell carcinoma patients with lung metastasis were treated with interleukin-2 (0.7 × 10(6) unit, 5 days a week) and interferon-α (6 × 10(6) IU, 3 days a week) for the first 8 weeks, and then with both interleukin-2 and interferon-α, 2 or 3 days a week for 16 additional weeks.

Results: Median follow-up period for 42 patients was 28.3 months (range: 4.2-43.8). Two-year overall survival rate was 82% and the probability of 3 year survival rate was 71%. Median progression-free survival was 10.4 months. While no difference was found in survival among patients assessed as complete response, partial response and no change, survival of patients assessed as NC or better was significantly better than those assessed as progressive disease (P < 0.0001). Furthermore, multivariate analyses identified pre-treatment serum sodium (P = 0.004) as an independent prognostic factor. The sodium level was also statistically associated with tumor response (p = 0.035). Patients with normal sodium level survived significantly longer (P = 0.0005) than those with low sodium level showing median survival of 12.2 months.

Conclusions: Combination immunotherapy with low-dose interleukin-2 plus interferon-α showed survival benefit for patients with lung metastasis whose tumor responded as no change or better. This combination immunotherapy could be beneficial for patients selected by metastatic organ and their pre-treatment serum sodium level.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / secondary*
  • Disease-Free Survival
  • Female
  • Humans
  • Immunologic Factors / therapeutic use
  • Interferon-alpha / administration & dosage
  • Interleukin-2 / administration & dosage
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / secondary*
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Sodium / blood
  • Treatment Outcome

Substances

  • Immunologic Factors
  • Interferon-alpha
  • Interleukin-2
  • Sodium