Phase 2 study of two sequential three-drug combinations containing bortezomib, cyclophosphamide and dexamethasone, followed by bortezomib, thalidomide and dexamethasone as frontline therapy for multiple myeloma.

Publication Type:

Journal Article

Source:

British journal of haematology, Volume 148, Issue 4, p.562-8 (2010)

Keywords:

2010, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Boronic Acids, Center-Authored Paper, Clinical Research Division, Cyclophosphamide, Dexamethasone, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Male, Middle Aged, Multiple Myeloma, Neoplasm Staging, Peripheral Blood Stem Cell Transplantation, Pyrazines, Survival Analysis, Thalidomide, Treatment Outcome

Abstract:

Novel sequential combination therapy for induction may improve the quality of response and therefore prolong survival in newly diagnosed multiple myeloma (MM) patients. We report results from a phase 2 study of two sequential three-drug combinations. Forty-four previously untreated, symptomatic MM patients received: bortezomib 1.3 mg/m(2) (days 1, 4, 8, 11), cyclophosphamide 300 mg/m(2) (days 1, 8), plus dexamethasone 40 mg (day of and day after bortezomib) for three 21-day cycles, followed by bortezomib 1.0 mg/m(2), dexamethasone 40 mg and thalidomide 100 mg daily for three cycles. Overall response rate for 42 evaluable patients was 95%, including 19% stringent complete response (sCR), 26% CR, and 57%>/= very good partial response. Twenty-two patients have undergone stem-cell transplantation. After a median follow-up of 20.9 months, five patients have died; none was induction therapy-related. Median event-free survival (EFS) and overall survival (OS) have not been reached; estimated 1-year EFS and OS rates were 81% and 91% respectively. Both three-drug combinations were well tolerated; 82% of patients completed all six cycles. Toxicities were predictable and manageable; the most-commonly reported grade 3/4 toxicity was neuropathy (11%). This novel sequential three-drug combination therapy is effective and well-tolerated in previously untreated MM patients.