TY - JOUR
T1 - Phase III evaluation of nortriptyline for alleviation of symptoms of cis-platinum-induced peripheral neuropathy
AU - Hammack, Julie E.
AU - Michalak, John C.
AU - Loprinzi, Charles L.
AU - Sloan, Jeff A.
AU - Novotny, Paul J.
AU - Soori, Gamini S.
AU - Tirona, Maria Tria
AU - Rowland, Kendrith M.
AU - Stella, Philip J.
AU - Johnson, Joanne A.
N1 - Funding Information:
This study was conducted as a collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic and was supported in part by Public Health Service grants CA-25224, CA-37404, CA-63849, CA-35195, CA-35103, CA-63848, CA-52352, CA-35269, CA-60276, CA-35103, CA-35415, CA-35101, CA-35448, and CA-35113. Additional participating institutions include: Duluth CCOP, Duluth, MN 55805 (James E. Krook); Iowa Oncology Research Association CCOP, Des Moines, IA 50314 (Roscoe F. Morton); Rapid City Regional Oncology Group, Rapid City, SD 59709 (Larry P. Ebbert); Mayo Clinic Scottsdale CCOP, Scottsdale, AZ 85259 (Robert F. Marschke Jr.); CentraCare Clinic, St. Cloud, MN 56301 (Harold E. Windschitl); Geisinger Clinical Oncology Program, Danville, PA 17822 (Suresh Nair); Grand Forks Clinic, Ltd., Grand Forks, ND 58201 (John A. Laurie); Siouxland Hematology-Oncology Associates, Sioux City, IA 51105 (John C. Michalak); Toledo Community Clinical Oncology Program, Toledo, OH 43610 (Paul L. Schaefer); and Illinois Oncology Research Assn. CCOP, Peoria, IL 61602 (John W. Kugler).
PY - 2002
Y1 - 2002
N2 - Tricyclic antidepressants have been reported to relieve the paresthesiae associated with peripheral neuropathies of many etiologies. We designed a randomized, double-blind, placebo-controlled, crossover trial to establish the efficacy of nortriptyline in the treatment of cis-diamminedichloroplatinum (CDDP)-induced paresthesiae. The study included 51 evaluable patients with CDDP-induced peripheral neuropathy and painful paresthesiae. The study consisted of two 4 week phases, separated by a 1 week 'wash-out' period, in which patients received escalating dosages of either placebo or nortriptyline. The target maximum dose of nortriptyline was 100 mg/day. Each patient filled out pre-randomization and then weekly questionnaires assessing paresthesiae severity, hours of sleep, quality of life, and adverse effects over the 9 week study. No significant differences in paresthesia were observed in the first treatment period between nortriptyline and placebo (means of 49 and 55 respectively on a 0-100 point scale, P=0.78). Although some evidence of a modest effect in favor of nortriptyline was observed during the second treatment period (about one patient in five got a 10-point reduction in pain from drug above placebo effect), this occurred in the presence of a strong carryover effect. Linear models analysis and Bayes methods confirmed that the effect of nortriptyline on paresthesia was modest at best. Hours of sleep increased in the nortriptyline phase (P=0.02). There was no significant difference in measures of quality of life and the effect of paresthesiae on patients' daily activities between nortriptyline and placebo. There was no major toxicity associated with nortriptyline, but dry mouth, dizziness, and constipation were more common with nortriptyline. In summary, nortriptyline failed to demonstrate strong evidence of any effect on paresthesia or pain. The presence of a potential effect which appeared in the second period of the crossover design is questionable due to the observed carryover effect. Cross-validation sensitivity analysis of results support the conclusion that nortriptyline provides modest improvement at best over placebo in terms of chemotherapy-related neuropathy.
AB - Tricyclic antidepressants have been reported to relieve the paresthesiae associated with peripheral neuropathies of many etiologies. We designed a randomized, double-blind, placebo-controlled, crossover trial to establish the efficacy of nortriptyline in the treatment of cis-diamminedichloroplatinum (CDDP)-induced paresthesiae. The study included 51 evaluable patients with CDDP-induced peripheral neuropathy and painful paresthesiae. The study consisted of two 4 week phases, separated by a 1 week 'wash-out' period, in which patients received escalating dosages of either placebo or nortriptyline. The target maximum dose of nortriptyline was 100 mg/day. Each patient filled out pre-randomization and then weekly questionnaires assessing paresthesiae severity, hours of sleep, quality of life, and adverse effects over the 9 week study. No significant differences in paresthesia were observed in the first treatment period between nortriptyline and placebo (means of 49 and 55 respectively on a 0-100 point scale, P=0.78). Although some evidence of a modest effect in favor of nortriptyline was observed during the second treatment period (about one patient in five got a 10-point reduction in pain from drug above placebo effect), this occurred in the presence of a strong carryover effect. Linear models analysis and Bayes methods confirmed that the effect of nortriptyline on paresthesia was modest at best. Hours of sleep increased in the nortriptyline phase (P=0.02). There was no significant difference in measures of quality of life and the effect of paresthesiae on patients' daily activities between nortriptyline and placebo. There was no major toxicity associated with nortriptyline, but dry mouth, dizziness, and constipation were more common with nortriptyline. In summary, nortriptyline failed to demonstrate strong evidence of any effect on paresthesia or pain. The presence of a potential effect which appeared in the second period of the crossover design is questionable due to the observed carryover effect. Cross-validation sensitivity analysis of results support the conclusion that nortriptyline provides modest improvement at best over placebo in terms of chemotherapy-related neuropathy.
KW - Cisplatinum
KW - Nortriptyline
KW - Peripheral neuropathy
UR - http://www.scopus.com/inward/record.url?scp=0036299151&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036299151&partnerID=8YFLogxK
U2 - 10.1016/S0304-3959(02)00047-7
DO - 10.1016/S0304-3959(02)00047-7
M3 - Article
C2 - 12098632
AN - SCOPUS:0036299151
SN - 0304-3959
VL - 98
SP - 195
EP - 203
JO - Pain
JF - Pain
IS - 1-2
ER -