Phase I/II study of bortezomib‐melphalan‐prednisolone for previously untreated Japanese patients with multiple myeloma
Open Access
- 11 April 2013
- journal article
- research article
- Published by Wiley in Cancer Science
- Vol. 104 (7), 912-919
- https://doi.org/10.1111/cas.12172
Abstract
This phase I/II study was conducted to evaluate the safety and efficacy of bortezomib‐melphalan‐prednisolone in Japanese patients with previously untreated multiple myeloma who are ineligible for hematopoietic stem cell transplantation. One hundred and one patients were enrolled, and 99 patients received up to nine 6‐week cycles of bortezomib (0.7/1.0/1.3 mg/m2) on days 1, 4, 8, 11, 22, 25, 29, and 32 in cycles 1–4 and on days 1, 8, 22, and 29 in cycles 5–9, with melphalan (9 mg/m2) and prednisolone (60 mg/m2) on days 1–4 of each cycle. The recommended dose was determined in the phase I portion, and the overall response rate and safety of bortezomib‐melphalan‐prednisolone at the recommended dose were assessed in the phase II portion. The recommended dose of bortezomib was determined to be 1.3 mg/m2. Grade 3 or higher non‐hematological adverse events included diarrhea (12%) and peripheral neuropathy (10%); grade 4 hematological adverse events included lymphopenia (41%), neutropenia (30%), and thrombocytopenia (22%). Eleven patients had lung injury associated with bortezomib; two had grade 3 disease, and the other nine had grade 1 or 2 disease. Of the 86 patients treated with 1.3‐mg/m2 bortezomib in phases I and II, the median number of treatment cycles was 4.5, and the overall response rate was 70% (95% confidence interval: 59–79%). Bortezomib‐melphalan‐prednisolone with 1.3‐mg/m2 bortezomib was considered to be tolerable and effective in Japanese patients with previously untreated multiple myeloma. However, further investigation is needed to refine the administration schedule.Keywords
This publication has 21 references indexed in Scilit:
- Guidelines for the diagnosis and management of multiple myeloma 2011British Journal of Haematology, 2011
- Multiple myeloma: 2011 update on diagnosis, risk‐stratification, and managementAmerican Journal of Hematology, 2010
- Bortezomib Plus Melphalan and Prednisone Compared With Melphalan and Prednisone in Previously Untreated Multiple Myeloma: Updated Follow-Up and Impact of Subsequent Therapy in the Phase III VISTA TrialJournal of Clinical Oncology, 2010
- Bortezomib plus Melphalan and Prednisone for Initial Treatment of Multiple MyelomaNew England Journal of Medicine, 2008
- Recent major improvement in long-term survival of younger patients with multiple myelomaBlood, 2008
- Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trialBlood, 2007
- Phase I and II pharmacokinetic and pharmacodynamic study of the proteasome inhibitor bortezomib in Japanese patients with relapsed or refractory multiple myelomaCancer Science, 2007
- Bortezomib or High-Dose Dexamethasone for Relapsed Multiple MyelomaNew England Journal of Medicine, 2005
- CRITERIA FOR EVALUATING DISEASE RESPONSE AND PROGRESSION IN PATIENTS WITH MULTIPLE MYELOMA TREATED BY HIGH‐DOSE THERAPY AND HAEMOPOIETIC STEM CELL TRANSPLANTATIONBritish Journal of Haematology, 1998
- A Prospective, Randomized Trial of Autologous Bone Marrow Transplantation and Chemotherapy in Multiple MyelomaNew England Journal of Medicine, 1996