Journal of Cancer Research and Clinical Oncology

, Volume 132, Issue 8, pp 499–504 | Cite as

Prospective randomized trial of natural interferon-alpha versus natural interferon-alpha plus cimetidine in advanced renal cell carcinoma with pulmonary metastasis

  • Toshiaki Kinouchi
  • Junichi Sakamoto
  • Taiji Tsukamoto
  • Hideyuki Akaza
  • Yoshinobu Kubota
  • Seiichiro Ozono
  • Hiroshi Kanetake
  • Tetsuo Taguchi
  • Toshihiko Kotake
  • Immunotherapy Oncology Group for Renal Cell Carcinoma
Original Paper


Purpose: In a preliminary non-randomized study, combination therapy with natural (i.e. non-recombinant) interferon-alpha plus cimetidine obtained a high response rate in patients with advanced renal cell carcinoma. We conducted a prospective randomized phase III trial to determine whether combination therapy with natural interferon-alpha plus cimetidine is superior to natural interferon-alpha alone in patients with advanced renal cell carcinoma with pulmonary metastasis. Methods: Patients received 5 million units (MU) natural interferon-alpha per day, five times a week, or the 5 MU natural interferon-alpha regimen plus a daily oral cimetidine. The primary and secondary end points were the response rate, and the time to progression (TTP), respectively. Results: Between April 1998 and March 2002, 71 patients from 32 institutions were randomly assigned to the 2 treatment groups. One patient in each group did not receive any natural interferon-alpha whatsoever. Two patients in the natural interferon-alpha alone group stopped treatment: on day 9 and on day 10, respectively. In the intent-to-treat analysis, 1 complete response (CR), 4 partial responses (PRs), 16 no changes (NCs), and 12 progressive diseases (PDs) were observed among the 36 patients in the interferon-alpha alone group with a response rate of 13.9%. Of the 35 patients in the natural interferon-alpha plus cimetidine group, there were two CRs, 8 PRs, 13 NCs, and 11 PDs, yielding a response rate of 28.6% (P=0.13). TTP ranged from 9 to 845 days (median 112 days) in the natural interferon-alpha-alone group, and from 31 to 1,568 days (median 125 days) in the natural interferon-alpha plus cimetidine group (P=0.87). Conclusions: Combined treatment with natural interferon-alpha plus cimetidine for advanced renal cell carcinoma did not result in a significant improvement in response rates or TTP compared to natural interferon-alpha therapy alone.


Cimetidine Natural interferon-alpha Pulmonary metastasis Renal cell carcinoma 



The authors are indebted to Prof. J. Patrick Barron of the international Medical Communications Center of Tokyo Medical University for his review of this manuscript.


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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Toshiaki Kinouchi
    • 1
  • Junichi Sakamoto
    • 2
  • Taiji Tsukamoto
    • 3
  • Hideyuki Akaza
    • 4
  • Yoshinobu Kubota
    • 5
  • Seiichiro Ozono
    • 6
  • Hiroshi Kanetake
    • 7
  • Tetsuo Taguchi
    • 8
  • Toshihiko Kotake
    • 1
  • Immunotherapy Oncology Group for Renal Cell Carcinoma
  1. 1.Department of UrologyOsaka Medical Center for Cancer and Cardiovascular DiseasesOsakaJapan
  2. 2.Kyoto University School of MedicineKyotoJapan
  3. 3.Sapporo Medical UniversitySapporoJapan
  4. 4.Tsukuba University School of MedicineTsukubaJapan
  5. 5.Yokohama City University School of MedicineYokohamaJapan
  6. 6.Hamamatsu University School of MedicineHamamatsuJapan
  7. 7.Nagasaki University School of MedicineNagasakiJapan
  8. 8.Japan Society for Cancer ChemotherapyOsakaJapan

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