Original Article

International Journal of Hematology

, Volume 92, Issue 3, pp 503-509

First online:

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

  • Yasushi TakamatsuAffiliated withDivision of Medical Oncology, Hematology and Infectious Diseases, Department of Medicine, Fukuoka University Email author 
  • , Kazutaka SunamiAffiliated withDepartment of Hematology, National Hospital Organization Okayama Medical Center
  • , Hiroyuki HataAffiliated withDepartment of Hematology, Kumamoto University of Medicine
  • , Koji NagafujiAffiliated withDepartment of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences
  • , Ilseung ChoiAffiliated withDepartment of Hematology, National Kyushu Cancer Center
  • , Masakazu HiguchiAffiliated withDepartment of Internal Medicine, Kyushu Kosei-Nenkin Hospital
  • , Kimiharu UozumiAffiliated withDepartment of Hematology and Immunology, Kagoshima University
  • , Yasufumi MasakiAffiliated withDepartment of Hematology and Immunology, Kanazawa Medical University
  • , Kazuo TamuraAffiliated withDivision of Medical Oncology, Hematology and Infectious Diseases, Department of Medicine, Fukuoka University
    • , The Kyushu Hematology Organization for Treatment Study Group (K-HOT)

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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