title: Good clinical activity and favorable toxicity profile of once weekly bortezomib, fotemustine, and dexamethasone (B-MuD) for the treatment of relapsed multiple myeloma.
abstract: Since multiple myeloma (MM) is still not-curable, the management of relapse remains challenging. Given the known efficacy of alkylating agents in MM, we conducted a phase I/II study to test a new three drug combination in which Fotemustine (Muphoran), an alkylating agent of nitrosurea family, was added to bortezomib + dexamethasone backbone (B-MuD) for the treatment of MM relapsed patients. Fotemustine was administered at two dose levels (80-100 mg/m² i.v.) on day 1. The original 21-day schedule was early amended for extra-hematological toxicity and a 35-day schedule was adopted (Bortezomib 1.3 mg/m² i.v. on days 1, 8, 15, and 22, Dexamethasone 20 mg i.v. on days 1, 8, 15, and 22) for a total of six courses. Twenty-four patients were enrolled. The maximum tolerated dose of Fotemustine was 100 mg/m². The overall response rate was of 62% (CR 8%, VGPR 33%, and PR 21%). The median OS was 28.5 months, the median progression-free survival (PFS) was 19.1 months. B-MuD resulted effective in patients previous exposed to bortezomib without difference of response (P = 0.25) and PFS (P = 0.87) when compared to bortezomib-naive patients. Thrombocytopenia was the most common AE overall. In conclusion, B-MuD is an effective and well tolerated combination in relapsed MM patients even in advanced disease phase.
authors.affiliation: Division of Hematology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy. silvia_mangiacavalli@hotmail.com
authors.forename: Silvia
authors.initials: S
authors.lastname: Mangiacavalli
authors.forename: Lara
authors.initials: L
authors.lastname: Pochintesta
authors.forename: Cristiana
authors.initials: C
authors.lastname: Pascutto
authors.forename: Federica
authors.initials: F
authors.lastname: Cocito
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pompa
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corso
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D009367:Neoplasm Staging; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000503:physiopathology; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055502:Secondary Prevention; D012720:Severity of Illness Index; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced / Q000503:physiopathology
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone; C054368:fotemustine