A phase II trial with gemcitabine and paclitaxel for the treatment of refractory and relapsed multiple myeloma patients

Multiple myeloma (MM) is an incurable disease with a 10-year survival of <20%. We have previously shown that the combination of gemcitabine and paclitaxel acts synergistically to induce apoptosis of myeloma cells in vitro. Based on these preclinical studies and phase I-II clinical trials in patients with solid tumors, we initiated a phase II clinical trial of paclitaxel 150 mg/m2 IV over 3 h followed by gemcitabine 3000 mg/m2 IV over 30-60 min in patients with relapsed or refractory MM. This regimen was administered every two weeks for a total of six cycles. Twelve patients enrolled, 3 discontinued treatment after 1 or 2 cycles because of severe neutropenia. As a result the protocol was modified to reduce the starting dose of gemcitabine to 2,000 mg/m2. This resulted in tolerable hematological and mild non-hematological toxicities in the rest of the patients. One patient died before the onset of treatment. Of the 8 remaining patients treated with a reduced dose of gemcitabine, 1 achieved a durable CR, 3 had PR, 1 had minor response (MR), 1 had stable disease and 2 had progressive disease. The CR patient had a 98% reduction in the M-protein, β2-microglobulin and plasma cells. His CR continued for more than 6 months. The 3 PR patients had a >50% reduction in the M-protein and >40% reduction in β2-microglobulin. Bone marrow plasma cells were reduced by >50% in these patients. Treatment with the combination of paclitaxel and gemcitabine is an active and well-tolerated regimen in patients with relapsed or refractory multiple myeloma.