Efficacy of lamotrigine in the management of chemotherapy-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled trial, N01C3.
BACKGROUND
Lamotrigine, an antiepileptic agent, has been reported as being effective in reducing symptoms of neuropathy associated with various etiologies. Based on such data, a multicenter double-blind, placebo-controlled, randomized trial was conducted to evaluate the effect of lamotrigine on pain and other neuropathic symptoms due to chemotherapy-induced peripheral neuropathy (CIPN).


METHODS
Patients with symptomatic CIPN with symptom scores of either 1) >3 on a 0-10 Numerical Rating Scale (NRS) or 2) >1 on the 0-3 the Eastern Cooperative Oncology Group (ECOG) neuropathy scale (ENS) were eligible (higher numbers corresponding to greater severity of symptoms in both scales). Patients were randomly assigned to receive lamotrigine (target dose of 300 mg/day) or placebo for 10 weeks. Endpoints were measured biweekly.


RESULTS
In all, 131 patients were enrolled. Both groups were well matched at baseline. Over the 10-week period of the trial, the average pain scores (NRS) for the lamotrigine and placebo arms declined in both arms, with no statistically significant difference noted between the changes in the 2 groups (0.3 and 0.5 unit reduction from baseline, respectively; P=.56). Similarly, decreases in the ENS with therapy were not statistically different (0.4 and 0.3, respectively; P=.3). Changes in other subjective symptom scales were also not found to be statistically different between the 2 groups. Toxicities were mild and similar in each group.


CONCLUSIONS
The results suggest that lamotrigine is not effective for relieving neuropathic symptoms in patients because of CIPN.
Rao
Ravi D
RD
Department of Medical Oncology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Flynn
Patrick J
PJ
Sloan
Jeff A
JA
Wong
Gilbert Y
GY
Novotny
Paul
P
Johnson
David B
DB
Gross
Howard M
HM
Renno
Samer I
SI
Nashawaty
Mohammed
M
Loprinzi
Charles L
CL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D004311:Double-Blind Method; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy*; D010919:Placebos; D014227:Triazines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D010919:Placebos; D014227:Triazines; D000077213:Lamotrigine