Phase II trial of sorafenib plus interferon alfa-2b as first- or second-line therapy in patients with metastatic renal cell cancer

J Clin Oncol. 2007 Aug 1;25(22):3288-95. doi: 10.1200/JCO.2007.10.8613.

Abstract

Purpose: We undertook this study to determine the activity and tolerability of sorafenib administered with interferon alfa-2b (IFN-alpha-2b) as first- or second-line therapy in metastatic renal cell cancer (RCC).

Patients and methods: Between November 2004 and October 2006, 40 patients at two sites were enrolled onto a phase II trial of sorafenib plus IFN-alpha-2b. Treatment consisted of 8-week cycles of sorafenib 400 mg orally bid plus IFN-alpha-2b 10 million U subcutaneously three times a week followed by a 2-week break. Patients were eligible to receive additional cycles of therapy until disease progression. Dose reduction of both drugs by 50% was permitted once for toxicity.

Results: The response rate was 33% (95% CI, 19% to 49%; 13 of 40 patients), including 28% partial responses (n = 11) and 5% complete responses (n = 2). Responses were seen in treatment-naïve and interleukin-2 (IL-2) -treated patients within the first two cycles. The median duration of response was 12 months. With a median follow-up time of 14 months, median progression-free survival time was 10 months (95% CI, 8 to 18 months), and median overall survival time has not yet been reached. Fatigue, anorexia, anemia, diarrhea, hypophosphatemia, rash, nausea, and weight loss were the most common toxicities. Grade 3 toxicities were uncommon but included hypophosphatemia, neutropenia, rash, fatigue, and anemia. Dose reductions were required in 65% of patients.

Conclusion: The combination of sorafenib and IFN-alpha-2b has substantial activity in treatment-naïve and IL-2-treated patients with RCC. The toxicity exceeded that of either drug alone, but dose reductions and breaks between cycles allowed for chronic therapy. A larger, randomized trial would determine whether there is any advantage to this regimen compared with sorafenib alone.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzenesulfonates / administration & dosage*
  • Benzenesulfonates / adverse effects
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / secondary*
  • Female
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / adverse effects
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Niacinamide / analogs & derivatives
  • North Carolina
  • Phenylurea Compounds
  • Pyridines / administration & dosage*
  • Pyridines / adverse effects
  • Recombinant Proteins
  • Sorafenib
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Benzenesulfonates
  • Interferon alpha-2
  • Interferon-alpha
  • Phenylurea Compounds
  • Pyridines
  • Recombinant Proteins
  • Niacinamide
  • Sorafenib