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

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Abstract

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.

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Acknowledgement

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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Authors and Affiliations

  1. Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka, 537-8511, Japan

    Toshiaki Kinouchi & Toshihiko Kotake

  2. Kyoto University School of Medicine, Kyoto, Japan

    Junichi Sakamoto

  3. Sapporo Medical University, Sapporo, Japan

    Taiji Tsukamoto

  4. Tsukuba University School of Medicine, Tsukuba, Japan

    Hideyuki Akaza

  5. Yokohama City University School of Medicine, Yokohama, Japan

    Yoshinobu Kubota

  6. Hamamatsu University School of Medicine, Hamamatsu, Japan

    Seiichiro Ozono

  7. Nagasaki University School of Medicine, Nagasaki, Japan

    Hiroshi Kanetake

  8. Japan Society for Cancer Chemotherapy, Osaka, Japan

    Tetsuo Taguchi

Authors
  1. Toshiaki Kinouchi
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  2. Junichi Sakamoto
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  3. Taiji Tsukamoto
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  4. Hideyuki Akaza
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  5. Yoshinobu Kubota
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  6. Seiichiro Ozono
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  7. Hiroshi Kanetake
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  8. Tetsuo Taguchi
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  9. Toshihiko Kotake
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Consortia

Immunotherapy Oncology Group for Renal Cell Carcinoma

Corresponding author

Correspondence to Toshiaki Kinouchi.

Appendix

Appendix

In addition to the authors, the following investigators and centers from the Immunotherapy Oncology Group for Renal Cell Carcinoma, Japan participated in this study: T. Koyanagi, N. Shinohara [Hokkaido University School of Medicine (University School of Medicine), Sapporo], N. Ito (Sapporo Medical University, Sapporo), T. Fujioka, S. Tanji (Iwate Medical University, Morioka), S. Orikasa, N. Hoshi (Tohoku University School of Medicine, Sendai), O. Yamaguchi, M. Ogiwara (Fukushima Medical University, Fukushima), K. Kawai (Tsukuba University School of Medicine, Tsukuba), H. Ito, T. Igarashi (Chiba University School of Medicine, Chiba), M. Murai, K. Marumo (Keio University School of Medicine, Shinjuku), M. Tachibana, Y. Ono (Tokyo Medical University, Shinjuku), H. Toma, H. Nakazawa (Tokyo Women’s Medical University, Shinjuku), M. Hosaka (Yokohama City University School of Medicine, Yokohama), K. Takahashi, Y. Tomita (Niigata University School of Medicine, Niigata), O. Ishizuka, T. Kashihara (Shinshu University School of Medicine, Matsumoto), M. Namiki, T. Uchibayashi (Kanazawa University School of Medicine, Kanazawa), N. Oshima, Y. Ono (Nagoya University School of Medicine, Nagoya), T. Kinukawa (Social Insurance Chukyo Hospital, Nagoya), Y. Hirao (Nara Medical University, Nara), T. Kishimoto, S. Ikemoto (Osaka City University School of Medicine, Osaka), S. Kamidono, A. Goto (Kobe University School of Medicine, Kobe), Y. Mori, T. Yoshimoto (Hyogo Medical University, Nishinomiya), H. Kumon, T. Tsushima (Okayama University School of Medicine, Okayama), M. Morioka, K. Kinukawa (Kawasaki Medical School, Kurashiki), M. Ikawa (Shimane Medical University, Izumo), T. Usui (Hiroshima University School of Medicine, Hiroshima), M. Kagawa, H. Kanayama (Tokushima University School of Medicine, Tokushima), S. Naito, N. Tokuda (Kyushu University School of Medicine, Fukuoka), H. Kanetake, N. Koga (Nagasaki University School of Medicine, Nagasaki), Y. Nagata (Miyazaki Medical College, Miyazaki), Y. Ogawa (Ryukyu University School of Medicine, Okinawa).

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Kinouchi, T., Sakamoto, J., Tsukamoto, T. et al. Prospective randomized trial of natural interferon-alpha versus natural interferon-alpha plus cimetidine in advanced renal cell carcinoma with pulmonary metastasis. J Cancer Res Clin Oncol 132, 499–504 (2006). https://doi.org/10.1007/s00432-006-0095-7

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  • DOI: https://doi.org/10.1007/s00432-006-0095-7

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