title: Bortezomib, low-dose intravenous melphalan, and dexamethasone for patients with relapsed multiple myeloma.
abstract: This multicenter phase I/II study investigated the maximum tolerated dose (MTD), safety, and efficacy of low dose intravenous (IV) melphalan in combination with bortezomib for patients with relapsed multiple myeloma (MM). Patients received bortezomib 1.3 mg/m(2) on days 1, 4, 8, and 11 and escalating doses of IV melphalan (2.5-10.0 mg/m(2)) on day 2 of a 28-day cycle for a maximum of eight cycles. Dexamethasone 20 mg was added for progressive or stable disease. Fifty-three patients were enrolled. The MTD was defined at melphalan 7.5 mg/m(2) and bortezomib 1.3 mg/m(2). The overall response rate (ORR) was 68% (23% complete or near-complete responses [CR/nCR]) whilst at the MTD (n = 33) the ORR was 76% (34% CR/nCR). After median follow-up of 17 months, the median progression free survival was 10 months, rising to 12 months at the MTD (P < 0.05 vs. non-MTD regimens). The median overall survival was 28 months, but was not yet reached at the MTD. Grade 3/4 adverse events included thrombocytopenia (62%), neutropenia (57%), infection (21%), and neuropathy (15%). Bortezomib and low-dose IV melphalan combination therapy is a safe and highly effective regimen for patients with relapsed MM. These data suggest further investigation of this combination is warranted.
authors.affiliation: Department of Haematology, St. Bartholomew's Hospital, London, UK. r.popat@qmul.ac.uk
authors.forename: Rakesh
authors.initials: R
authors.lastname: Popat
authors.forename: Heather
authors.initials: H
authors.lastname: Oakervee
authors.forename: Catherine
authors.initials: C
authors.lastname: Williams
authors.forename: Mark
authors.initials: M
authors.lastname: Cook
authors.forename: Charles
authors.initials: C
authors.lastname: Craddock
authors.forename: Supratik
authors.initials: S
authors.lastname: Basu
authors.forename: Charles
authors.initials: C
authors.lastname: Singer
authors.forename: Stephen
authors.initials: S
authors.lastname: Harding
authors.forename: Nicola
authors.initials: N
authors.lastname: Foot
authors.forename: Simon
authors.initials: S
authors.lastname: Hallam
authors.forename: Liz
authors.initials: L
authors.lastname: Odeh
authors.forename: Simon
authors.initials: S
authors.lastname: Joel
authors.forename: Jamie
authors.initials: J
authors.lastname: Cavenagh
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / 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; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012008:Recurrence; D018709:Statistics, Nonparametric; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone; D008558:Melphalan