title: A phase II trial with gemcitabine and paclitaxel for the treatment of refractory and relapsed multiple myeloma patients.
abstract: 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/m(2) IV over 3 h followed by gemcitabine 3000 mg/m(2) 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/m(2). 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, beta2-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 beta2-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.
authors.affiliation: Department of Medicine/Hematology, University of Texas Health Science Center, San Antonio, TX 78284, USA. gazitt@uthscsa.edu
authors.forename: Yair
authors.initials: Y
authors.lastname: Gazitt
authors.forename: Paul
authors.initials: P
authors.lastname: Shaughnessy
authors.forename: Mace L
authors.initials: ML
authors.lastname: Rothenberg
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage*; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D017239:Paclitaxel; D000093542:Gemcitabine