title: A phase 1 study of IPI-504 (retaspimycin hydrochloride) in patients with relapsed or relapsed and refractory multiple myeloma.
abstract: Abstract   A phase 1 study of IPI-504 (retaspimycin hydrochloride) administered intravenously twice weekly for 2 weeks at 22.5, 45, 90, 150, 225, 300 or 400 mg/m(2) followed by 10 days off-treatment was conducted to determine the safety and maximum tolerated dose (MTD) of IPI-504 in patients with relapsed or relapsed/refractory multiple myeloma (MM). Anti-tumor activity and pharmacokinetics were also evaluated. Eighteen patients (mean age 60.5 years; median 9 prior therapies) were enrolled. No dose-limiting toxicities (DLTs) were reported for IPI-504 doses up to 400 mg/m(2). The most common treatment-related adverse event was grade 1 infusion site pain (four patients). All other treatment-related events were assessed as grade 1 or 2 in severity. The area under the curve (AUC) increased with increasing dose, and the mean half-life was approximately 2-4 h for IPI-504 and its metabolites. Four patients had stable disease, demonstrating modest single-agent activity in relapsed or relapsed/refractory MM.
authors.affiliation: Hackensack University Medical Center, Hackensack, NJ 07601, USA. DSiegel@humed.com
authors.forename: David
authors.initials: D
authors.lastname: Siegel
authors.forename: Sundar
authors.initials: S
authors.lastname: Jagannath
authors.forename: David H
authors.initials: DH
authors.lastname: Vesole
authors.forename: Ivan
authors.initials: I
authors.lastname: Borello
authors.forename: Amitabha
authors.initials: A
authors.lastname: Mazumder
authors.forename: Constantine
authors.initials: C
authors.lastname: Mitsiades
authors.forename: Jill
authors.initials: J
authors.lastname: Goddard
authors.forename: Joi
authors.initials: J
authors.lastname: Dunbar
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Normant
authors.forename: Julian
authors.initials: J
authors.lastname: Adams
authors.forename: David
authors.initials: D
authors.lastname: Grayzel
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: Paul
authors.initials: P
authors.lastname: Richardson
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016227:Benzoquinones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D047029:Lactams, Macrocyclic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D047029:Lactams, Macrocyclic; C112765:tanespimycin