title: Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase III APEX trial in relapsed multiple myeloma: impact of a dose-modification guideline.
abstract: The frequency, characteristics and reversibility of bortezomib-associated peripheral neuropathy were evaluated in the phase III APEX (Assessment of Proteasome Inhibition for Extending Remissions) trial in patients with relapsed myeloma, and the impact of a dose-modification guideline on peripheral neuropathy severity and reversibility was assessed. Patients received bortezomib 1.3 mg/m(2) (days 1, 4, 8, 11, eight 21-d cycles, then days 1, 8, 15, 22, three 35-d cycles); bortezomib was held, dose-reduced or discontinued depending on peripheral neuropathy severity, according to a protocol-specified dose-modification guideline. Overall, 124/331 patients (37%) had treatment-emergent peripheral neuropathy, including 30 (9%) with grade >or=3; incidence and severity were not affected by age, number/type of prior therapies, baseline glycosylated haemoglobin level, or diabetes history. Grade >or=3 incidence appeared lower versus phase II trials (13%) that did not specifically provide dose-modification guidelines. Of patients with grade >or=2 peripheral neuropathy, 58/91 (64%) experienced improvement or resolution to baseline at a median of 110 d, including 49/72 (68%) who had dose modification versus 9/19 (47%) who did not. Efficacy did not appear adversely affected by dose modification for grade >or=2 peripheral neuropathy. Bortezomib-associated peripheral neuropathy is manageable and reversible in most patients with relapsed myeloma. Dose modification using a specific guideline improves peripheral neuropathy management without adversely affecting outcome.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA 02115, USA. Paul_Richardson@dfci.harvard.edu
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.forename: Michael W
authors.initials: MW
authors.lastname: Schuster
authors.forename: Edward A
authors.initials: EA
authors.lastname: Stadtmauer
authors.forename: Thierry
authors.initials: T
authors.lastname: Facon
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Harousseau
authors.forename: Dina
authors.initials: D
authors.lastname: Ben-Yehuda
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.forename: Donna
authors.initials: D
authors.lastname: Reece
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
authors.forename: Jamie D
authors.initials: JD
authors.lastname: Cavenagh
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Boral
authors.forename: Dixie-Lee
authors.initials: DL
authors.lastname: Esseltine
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Amato
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: Jesus
authors.initials: J
authors.lastname: San Miguel
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D002985:Clinical Protocols; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy*; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D018709:Statistics, Nonparametric; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib