title: 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.
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.
authors.affiliation: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., Seattle, WA 98109, USA. wbensing@fhcrc.org
authors.forename: William I
authors.initials: WI
authors.lastname: Bensinger
authors.forename: Sundar
authors.initials: S
authors.lastname: Jagannath
authors.forename: Robert
authors.initials: R
authors.lastname: Vescio
authors.forename: Elber
authors.initials: E
authors.lastname: Camacho
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wolf
authors.forename: David
authors.initials: D
authors.lastname: Irwin
authors.forename: Gerardo
authors.initials: G
authors.lastname: Capo
authors.forename: Marti
authors.initials: M
authors.lastname: McKinley
authors.forename: Phyllis
authors.initials: P
authors.lastname: Potts
authors.forename: David H
authors.initials: DH
authors.lastname: Vesole
authors.forename: Amitabha
authors.initials: A
authors.lastname: Mazumder
authors.forename: John
authors.initials: J
authors.lastname: Crowley
authors.forename: Pam
authors.initials: P
authors.lastname: Becker
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Hilger
authors.forename: Brian G M
authors.initials: BG
authors.lastname: Durie
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D036102:Peripheral Blood Stem Cell Transplantation; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D003520:Cyclophosphamide