Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase III APEX trial in relapsed multiple myeloma: impact of a dose-modification guideline.
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.
Richardson
Paul G
PG
Dana-Farber Cancer Institute, Boston, MA 02115, USA. Paul_Richardson@dfci.harvard.edu
Sonneveld
Pieter
P
Schuster
Michael W
MW
Stadtmauer
Edward A
EA
Facon
Thierry
T
Harousseau
Jean-Luc
JL
Ben-Yehuda
Dina
D
Lonial
Sagar
S
Goldschmidt
Hartmut
H
Reece
Donna
D
Bladé
Joan
J
Boccadoro
Mario
M
Cavenagh
Jamie D
JD
Boral
Anthony L
AL
Esseltine
Dixie-Lee
DL
Wen
Patrick Y
PY
Amato
Anthony A
AA
Anderson
Kenneth C
KC
San Miguel
Jesus
J
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
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib