International Journal of Hematology

, Volume 80, Issue 4, pp 341–350 | Cite as

A Randomized Controlled Trial Investigating the Survival Benefit of Dose-Intensified Multidrug Combination Chemotherapy (LSG9) for Intermediate- or High-Grade Non-Hodgkin’s Lymphoma: Japan Clinical Oncology Group Study 9002

  • Tomohiro Kinoshita
  • Tomomitsu Hotta
  • Kensei Tobinai
  • Tohru Kobayashi
  • Naoki Ishizuka
  • Masao Tomonaga
  • Toshiaki Sai
  • Youichiro Ohno
  • Masaharu Kasai
  • Michinori Ogura
  • Chikara Mikuni
  • Hironobu Toki
  • Masayuki Sano
  • Yasufumi Masaki
  • Tomoko Ohtsu
  • Yoshihiro Matsuno
  • Takeaki Takenaka
  • Shigeru Shirakawa
  • Masanori Shimoyama
  • Lymphoma Study Group of the Japan Clinical Oncology Group (JCOG-LSG)


The effect of enhancing the dose intensity (DI) of the key drugs in multidrug combination chemotherapy for malignant lymphoma is uncertain. We investigated the survival benefit of dose-intensified multidrug combination chemotherapy for intermediate- or high-grade non-Hodgkin’s lymphoma (NHL). Patients without any prior chemotherapy were randomly assigned either to dose-intensified multidrug combination chemotherapy, LSG9 (VEPA-B/FEPP-AB/M-FEPA, treated 3 times every 10 weeks for 28 weeks total), or to control-arm combination chemotherapy, mLSG4 (VEPA-B/FEPP-B/M-FEPA, treated 4 times every 14 weeks for 54 weeks total). The planned DI of doxorubicin and cyclophosphamide were 1.96 and 1.47 times higher, respectively, in LSG9 than in mLSG4. Overall survival, complete response (CR) rate, and toxicities were evaluated. The 447 patients (230 for LSG9 and 217 for mLSG4) were enrolled between February 1991 and March 1995.The 5-year overall survival rates were 56.8% for LSG9 patients and 55.1% for mLSG4 patients (log-rank P =.42).The rates for CR plus uncertain CR were 70.0% for LSG9 and 64.5% for mLSG4. The toxicities of both regimens were similar and tolerable. The median actual DI of doxorubicin and cyclophosphamide were 1.56 and 1.17 times higher, respectively, in LSG9 than in mLSG4. Compared with the control regimen mLSG4, the dose-intensified regimen LSG9 did not show significant survival benefit. An increase in the DI of doxorubicin in multidrug combination chemotherapy did not improve the survival of patients with intermediate- or high-grade NHL.

Key words

Non-Hodgkin’s lymphoma Combination chemotherapy Dose intensity Doxorubicin Randomized controlled trial 


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Copyright information

© The Japanese Society of Hematology 2004

Authors and Affiliations

  • Tomohiro Kinoshita
    • 1
  • Tomomitsu Hotta
    • 2
  • Kensei Tobinai
    • 3
  • Tohru Kobayashi
    • 4
  • Naoki Ishizuka
    • 5
  • Masao Tomonaga
    • 6
  • Toshiaki Sai
    • 7
  • Youichiro Ohno
    • 8
  • Masaharu Kasai
    • 9
  • Michinori Ogura
    • 10
  • Chikara Mikuni
    • 11
  • Hironobu Toki
    • 12
  • Masayuki Sano
    • 13
  • Yasufumi Masaki
    • 14
  • Tomoko Ohtsu
    • 15
  • Yoshihiro Matsuno
    • 3
  • Takeaki Takenaka
    • 3
  • Shigeru Shirakawa
    • 4
  • Masanori Shimoyama
    • 3
  • Lymphoma Study Group of the Japan Clinical Oncology Group (JCOG-LSG)
  1. 1.Department of HematologyNagoya University Graduate School of MedicineShowa-ku, NagoyaJapan
  2. 2.Tokai UniversityIsehara
  3. 3.National Cancer Center HospitalTokyo
  4. 4.Mie University School of MedicineTsu
  5. 5.National Cancer Center Research InstituteTokyo
  6. 6.Nagasaki UniversityNagasaki
  7. 7.Iwaki Kyoritsu General HospitalIwaki
  8. 8.Tenri HospitalTenri
  9. 9.Sapporo Hokuyu HospitalSapporo
  10. 10.Aichi Cancer CenterNagoya
  11. 11.Sapporo National HospitalSapporo
  12. 12.National Shikoku Cancer CenterMatsuyama
  13. 13.Saga Medical SchoolSaga
  14. 14.Kanazawa Medical UniversityKanazawa
  15. 15.National Cancer Center Hospital EastKashiwaJapan

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