Erschienen in:
01.10.2010 | Original Article
A phase I study of bortezomib in combination with doxorubicin and intermediate-dose dexamethasone (iPAD therapy) for relapsed or refractory multiple myeloma
verfasst von:
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)
Erschienen in:
International Journal of Hematology
|
Ausgabe 3/2010
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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.