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Nation-wide randomized comparative study of doxorubicin, vincristine and prednisolone combination therapy with and without L-asparaginase for adult acute lymphoblastic leukemia

  • Original Articles
  • ADVP, L-Asparaginase, Acute Lymphoblastic Leukemia
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Abstract

A randomized clinical trial of combination chemotherapy for adult acute lymphoblastic leukemia (ALL) with doxorubicin, vincristine and prednisolone with and withoutL-asparaginase (AdVP vs L-AdVP) was conducted, involving 58 institutions throughout Japan. After reaching complete remission (CR), patients were treated with the same regimen for more than 2 years. Among 166 evaluable cases of the 198 cases enrolled, CR rates were 63.1% (53/84) with AdVP and 64.6% (53/82) with L-AdVP (P=0.837). Median survival times and 7-year survival rates were 12.7 months and 21.2% with AdVP, and 16.0 months and 22.3% with L-AdVP (P=0.955 by generalized Wilcoxon test [GW],P=0.952 by log-rank test [LR]). Median diseasefree survival times and 7-year survival rates were 13.5 months and 23.8% with AdVP and 17.0 months and 30.6% with L-AdVP, showing some increments for L-AdVP but no statistical significance (P=0.141 by GW,P=0.300 by LR). Among the cases of extramurally confirmed FAB subtypes, CR rates were 75.9% (63/83) for the L1 subtype and 51.3% (39/76) for the L2 subtype (P=0.001). As to adverse effects, pancreatitis was complicated more frequently in L-AdVP than in AdVP (P=0.039). Other side effects such as hyperbilirubinemia, diabetes mellitus, diarrhea and hypofibrinogenemia were observed more frequently with L-AdVP, but with no statistical significance. Thus, addition of a single course of L-asparaginase in the induction phase of combination chemotherapy with doxorubicin, vincristine and prednisolone did not significantly enhance the effect of antileukemic treatment of adult ALL.

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Authors and Affiliations

  1. Department of Internal Medicine, Chubu National Hospital, 36-3, Gengo, Morioka-cho, 474, Obu-shi, Alchi-ken, Japan

    Eiichi Nagura

  2. Nagoya National Hospital, Nagoya, Japan

    Kiyoji Kimura

  3. Department of Internal Medicine, Branch Hospital, Nagoya University School of Medicine, Nagoya, Japan

    Kazumasa Yamada

  4. Aighi Cancer Center Hospital, Nagoya, Japan

    Kazuo Ota

  5. Third Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan

    Tadashi Maekawa

  6. Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan

    Fumimaro Takaku

  7. First Department of Internal Medicine, School of Medicine, Kyoto University, Kyoto, Japan

    Haruto Uchino

  8. Fifth Department of Internal Medicine, Center for Adult Disease, Osaka, Japan

    Toru Masaoka

  9. First Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan

    Ichita Amaki

  10. First Department of Internal Medicine, Department of Clinical Laboratory, Nagoya University School of Medicine, Nagoya, Japan

    Kohei Kawashima

  11. First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan

    Ryuzo Ohno

  12. Third Department of Internal Medicine, Nippon Medical School, Tokyo, Japan

    Takeo Nomura

  13. Third Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Japan

    Jun-ichi Hattori

  14. First Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan

    Setsuko Kawamura

  15. First Department of Internal Medicine, Niigata University School of Medicine, Niigata, Japan

    Akira Shibata

  16. Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan

    Shigeru Shirakawa

  17. Department of Public Health, Gifu University School of Medicine, Gifu, Japan

    Nobuyuki Hamajima

Authors
  1. Eiichi Nagura
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  2. Kiyoji Kimura
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  3. Kazumasa Yamada
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  4. Kazuo Ota
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  5. Tadashi Maekawa
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  6. Fumimaro Takaku
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  7. Haruto Uchino
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  8. Toru Masaoka
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  9. Ichita Amaki
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  10. Kohei Kawashima
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  11. Ryuzo Ohno
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  12. Takeo Nomura
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  13. Jun-ichi Hattori
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  14. Setsuko Kawamura
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  15. Akira Shibata
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  16. Shigeru Shirakawa
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  17. Nobuyuki Hamajima
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Additional information

This work was supported by a grant-in-aid from the Japanese Foundation for Multidisciplinary Treatment of Cancer (Co-operative Project no. 2)

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Nagura, E., Kimura, K., Yamada, K. et al. Nation-wide randomized comparative study of doxorubicin, vincristine and prednisolone combination therapy with and without L-asparaginase for adult acute lymphoblastic leukemia. Cancer Chemother. Pharmacol. 33, 359–365 (1994). https://doi.org/10.1007/BF00686263

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  • DOI: https://doi.org/10.1007/BF00686263

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