Phase-II trial of combination treatment of interferon-α, cimetidine, cyclooxygenase-2 inhibitor and renin-angiotensin-system inhibitor (I-CCA therapy) for advanced renal cell carcinoma

Cancer Sci. 2011 Jan;102(1):137-43. doi: 10.1111/j.1349-7006.2010.01756.x. Epub 2010 Oct 26.


We have recently reported favorable responses to a combination treatment comprising cimetidine, a cyclooxygenase-2 inhibitor and a renin-angiotensin-system inhibitor in metastatic renal cell carcinoma (RCC). In view of the potential synergistic effects of these three agents and interferon-α (I-CCA therapy), we conducted a phase-II trial to examine the efficacy and toxicity of I-CCA as first-line treatment. Fifty-one patients with advanced RCC received natural interferon-α (3-6 million U thrice/week) and cimetidine (800 mg), cyclooxygenase-2 inhibitor meloxicam (10 mg), and renin-angiotensin-system inhibitor candesartan (4 mg) or perindopril (4 mg) orally daily. Memorial Sloan-Kettering Cancer Center prognostic categories were favorable, intermediate and poor in 10 (20%), 31 (61%) and 10 (20%) patients, respectively. The primary end-point was the objective response rate (ORR) and the secondary end-points included clinical benefit, progression-free survival (PFS), overall survival (OS) and safety. Median follow-up was 19 months. Complete response (CR) was observed in four patients (8%) and partial response in seven (14%), yielding an ORR of 22%. None of the four patients who achieved CR relapsed during the 16- to 81-month follow up. The ORR were 17% in the favorable- or intermediate-risk group and 40% in the poor-risk group. The other 24 patients (45%) had stable disease for at least 6 months, resulting in a clinical benefit rate of 67%. The median PFS and OS were 12 and 30 months, respectively. Grade 3/4 toxicities were never observed. The I-CCA therapy, providing favorable responses and low toxicity profiles, is worthy of further consideration as a first-line therapy for metastatic RCC.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzimidazoles / administration & dosage
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / mortality
  • Cimetidine / administration & dosage
  • Cyclooxygenase 2 Inhibitors / administration & dosage
  • Disease-Free Survival
  • Female
  • Humans
  • Interferon-alpha / administration & dosage
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / mortality
  • Male
  • Middle Aged
  • Perindopril / administration & dosage
  • Tetrazoles / administration & dosage


  • Benzimidazoles
  • Cyclooxygenase 2 Inhibitors
  • Interferon-alpha
  • Tetrazoles
  • Cimetidine
  • candesartan
  • Perindopril