International Journal of Hematology

, Volume 92, Issue 3, pp 503–509

A phase I study of bortezomib in combination with doxorubicin and intermediate-dose dexamethasone (iPAD therapy) for relapsed or refractory multiple myeloma

  • Yasushi Takamatsu
  • Kazutaka Sunami
  • Hiroyuki Hata
  • Koji Nagafuji
  • Ilseung Choi
  • Masakazu Higuchi
  • Kimiharu Uozumi
  • Yasufumi Masaki
  • Kazuo Tamura
  • The Kyushu Hematology Organization for Treatment Study Group (K-HOT)
Original Article

Abstract

Bortezomib and doxorubicin have synergistic activity against myeloma cells in vitro. We underwent a dose finding study of bortezomib in combination with a fixed dose of doxorubicin and intermediate-dose dexamethasone (iPAD therapy) in patients with relapsed or refractory myeloma. Bortezomib was administered on days 1, 4, 8 and 11 at a dose of 1.0 and 1.3 mg/m2 in cohorts 1 and 2, respectively. Doxorubicin 9 mg/m2 was given by rapid intravenous infusion on days 1–4, and dexamethasone 20 mg on days 1–2, 4–5, 8–9 and 11–12. Treatment was repeated at a 3-week interval and the dose-limiting toxicity (DLT), defined as grade 4 hematological toxicity lasting more than 5 days and/or grade 3 or higher non-hematological toxicity, was evaluated. In cohort 1, 2 of 6 patients developed DLTs including grade 4 hyponatremia and grade 3 infection with appropriate neutrophil counts. No DLT was observed in the remaining 4 patients, indicating this dose was tolerable. In cohort 2, 3 of 5 patients developed DLTs including grade 4 thrombocytopenia lasting more than 5 days, grade 3 hepatic transaminase elevation and grade 3 ileus, indicating this dose was intolerable. It is concluded that bortezomib at the dose of 1.0 mg/m2 is recommended in combination with doxorubicin and intermediate-dose dexamethasone.

Keywords

Bortezomib Doxorubicin Myeloma Phase 1 trial 

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Copyright information

© The Japanese Society of Hematology 2010

Authors and Affiliations

  • Yasushi Takamatsu
    • 1
  • Kazutaka Sunami
    • 2
  • Hiroyuki Hata
    • 3
  • Koji Nagafuji
    • 4
  • Ilseung Choi
    • 5
  • Masakazu Higuchi
    • 6
  • Kimiharu Uozumi
    • 7
  • Yasufumi Masaki
    • 8
  • Kazuo Tamura
    • 1
  • The Kyushu Hematology Organization for Treatment Study Group (K-HOT)
  1. 1.Division of Medical Oncology, Hematology and Infectious Diseases, Department of MedicineFukuoka UniversityFukuokaJapan
  2. 2.Department of HematologyNational Hospital Organization Okayama Medical CenterOkayamaJapan
  3. 3.Department of HematologyKumamoto University of MedicineKumamotoJapan
  4. 4.Department of Medicine and Biosystemic ScienceKyushu University Graduate School of Medical SciencesFukuokaJapan
  5. 5.Department of HematologyNational Kyushu Cancer CenterFukuokaJapan
  6. 6.Department of Internal MedicineKyushu Kosei-Nenkin HospitalKitakyushuJapan
  7. 7.Department of Hematology and ImmunologyKagoshima UniversityKagoshimaJapan
  8. 8.Department of Hematology and ImmunologyKanazawa Medical UniversityKanazawaJapan

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