We previously conducted a phase 1 study of bortezomib, doxorubicin and intermediate-dose dexamethasone (iPAD) therapy and determined the optimal dose of bortezomib to be 1.0 mg/m2. We then conducted a multicenter phase 2 study in patients with relapsed or refractory myeloma. Bortezomib 1.0 mg/m2 was administered intravenously on days 1, 4, 8 and 11, in combination with intravenous doxorubicin 9 mg/m2 on days 1-4, and dexamethasone 20 mg orally on days 1-2, 4-5, 8-9 and 11-12 at a 3-week interval for six cycles. The primary endpoint of this study was the complete remission (CR) rate, and the secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicity. Twenty-seven patients, median age of 63, were enrolled. An overall response rate was 89 % with CR rate of 30 %. The median PFS time was 12.1 months, and the median OS time was not reached. One patient died of pneumonia. Although the incidence of hematological toxicities was high, these were transient and manageable. The most common non-hematological toxicity was sensory neuropathy; grade 3 toxicity was observed in six patients (22 %) and treatment was discontinued in four. We conclude that iPAD therapy is feasible, and shows efficacy by inducing high response rates and long response duration.
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