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Phase III Study of Ranimustine, Cyclophosphamide, Vincristine, Melphalan, and Prednisolone (MCNU-COP/MP) versus Modified COP/MP in Multiple Myeloma: A Japan Clinical Oncology Group Study, JCOG 9301

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Abstract

To investigate whether combination chemotherapy with vincristine, cyclophosphamide, prednisolone, and melphalan (COP/ MP) with the addition of ranimustine (MCNU) (MCNU-COP/MP) is superior to the slightly modified COP/MP (mCOP/MP) regimen in multiple myeloma (MM), a multicenter randomized study was performed. Two hundred ten patients with newly diagnosed, overt MM not treated with chemotherapy were enrolled from 32 institutions of the Lymphoma Study Group of the Japan Clinical Oncology Group and were randomized to receive either MCNU-COP/MP or mCOP/MP. The response rate (RR) to mCOP/MP was 43.7% (95% confidence interval [CI], 33.9%–53.8%] and to MCNU-COP/MP was 56.1 % (95% CI, 46.1 %–65.7%) (P = .097). The progression-free survival (PFS) was significantly longer for patients treated with MCNU-COP/MP than for patients treated with mCOP/MP (median, 23.0 months [95% CI, 18.9–25.8] versus 15.8 months [95% CI, 14.1–19.4]) (P = .014). However, no significant difference in overall survival rate (OS) was observed between the groups (median, 49.9 months [95% CI, 40.4-59.1] versus 44.0 months [95% CI, 32.8–59.8]) ( P = .75). Grades 3 and 4 hematological toxicities were more frequently observed with MCNU-COP/MP than with mCOP/MP, but the incidence of grades 3 and 4 nonhematological toxicities was low in both groups. In conclusion, MCNU-COP/MP in comparison with mCOP/MP improved RR and PFS in overt MM; however, this outcome did not contribute to prolonging OS, indicating that addition of MCNU to mCOP/MP has no benefit on survival.

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Author information

Authors and Affiliations

  1. Hematology Division, National Cancer Center Hospital, Tokyo

    Takeaki Takenaka

  2. Division of Hematology/Oncology, National Cancer Center Hospital East, Kashiwa

    Kuniaki Itoh

  3. Division of Hematology/Oncology, Shiga Medical Center for Adults, Shiga

    Takayo Suzuki

  4. Department of Internal Medicine, Imamura Bun- in Hospital, Kagoshima

    Atae Utsunomiya

  5. Ohla Nishinouchi Hospital, Koriyama

    Shin Matsuda

  6. Departments of Internal Medicine, Niigata Cancer Center Niigata Hospital, Niigata

    Takaaki Chou

  7. Iwaki- Kyoritsu General Hospital, Iwaki

    Toshiaki Sai

  8. Saga Medical School, Saga

    Masayuki Sano

  9. Department of Hematology and Immunology, Kanazawa Medical University, Kahoku

    Susumu Konda

  10. Departments of Internal Medicine, Ohtsu Red Cross Hospital, Ohtsu

    Tatsuji Ohno

  11. Sapporo National Hospital, Sapporo

    Chikara Mikuni

  12. Saku Central Hospital, Saku

    Kijoh Deura

  13. Jikei University Aoto Hospital, Tokyo

    Takashi Yamada

  14. Daisan Hospital, Jikei University, Komae

    Fumi Mizorogi

  15. St, Marianna University Hospital, Kawasaki

    Haruhisa Nagoshi

  16. Department of Hematology, Molecular Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki

    Masao Tomonaga

  17. Fourth Department of Internal Medicine, Tokai University, Isehara

    Tomomitsu Hotta

  18. Department of Internal Medicine, Kyorin University, Mitaka

    Kohichi Kawano

  19. Departments of Hematology, Nagoya National Hospital, Nagoya

    Keitaro Tsushita

  20. Fujita Health University, Toyoake

    Masami Hirano

  21. Medical Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, 104-0045, Tokyo, Japan

    Masanori Shimoyama

Authors
  1. Takeaki Takenaka
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  2. Kuniaki Itoh
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  3. Takayo Suzuki
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  4. Atae Utsunomiya
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  5. Shin Matsuda
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  15. Haruhisa Nagoshi
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  16. Masao Tomonaga
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  17. Tomomitsu Hotta
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  21. Masanori Shimoyama
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Lymphoma Study Group of the Japan Clinical Oncology Group

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Correspondence to Masanori Shimoyama.

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Takenaka, T., Itoh, K., Suzuki, T. et al. Phase III Study of Ranimustine, Cyclophosphamide, Vincristine, Melphalan, and Prednisolone (MCNU-COP/MP) versus Modified COP/MP in Multiple Myeloma: A Japan Clinical Oncology Group Study, JCOG 9301. Int J Hematol 79, 165–173 (2004). https://doi.org/10.1532/IJH97.03115

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  • DOI: https://doi.org/10.1532/IJH97.03115

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