Ketotifen for Preventing Oxaliplatin-Induced Neuropathy in Stage III Colorectal Cancer: a Randomized Controlled Trial.
Oxaliplatin-induced peripheral neuropathy (OIPN) is a frequent, dose-limiting toxicity in colorectal cancer and markedly impairs quality of life. This study aimed to evaluate the protective role of ketotifen in preventing OIPN, considering its mast-cell stabilizing, histamine H1 receptor-blocking, anti-inflammatory, and analgesic properties demonstrated in preclinical models.
In this randomized controlled trial, 64 patients with stage III colorectal cancer were assigned to two groups. The control group (n = 32) received the standard mFOLFOX-6 regimen for 12 cycles, whereas the ketotifen group (n = 32) received the same regimen plus ketotifen 2 mg orally once daily. Neuropathy prevention was assessed through serum biomarkers (neurotensin, superoxide dismutase, interleukin-6), the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0), the 12-item neurotoxicity questionnaire (Ntx-12), and the Brief Pain Inventory-Short Form (BPI-SF).
After 12 cycles, the ketotifen group showed a significant reduction in interleukin-6 and neurotensin levels (p < 0.0001), a lower incidence of grade 2-3 neuropathy (p = 0.001), reduced pain severity (p < 0.0001), and better Ntx-12 scores (p < 0.0001) compared with controls. Ketotifen was well tolerated and improved quality of sleep and appetite (p < 0.0001), addressing additional patient-reported challenges.
This trial indicates that ketotifen may offer a promising approach for preventing OIPN. Larger placebo-controlled, double-blind, multicenter trials are needed to confirm these findings.
NCT05624138.
1-11-2022.
36030/11/22.
In this randomized controlled trial, 64 patients with stage III colorectal cancer were assigned to two groups. The control group (n = 32) received the standard mFOLFOX-6 regimen for 12 cycles, whereas the ketotifen group (n = 32) received the same regimen plus ketotifen 2 mg orally once daily. Neuropathy prevention was assessed through serum biomarkers (neurotensin, superoxide dismutase, interleukin-6), the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0), the 12-item neurotoxicity questionnaire (Ntx-12), and the Brief Pain Inventory-Short Form (BPI-SF).
After 12 cycles, the ketotifen group showed a significant reduction in interleukin-6 and neurotensin levels (p < 0.0001), a lower incidence of grade 2-3 neuropathy (p = 0.001), reduced pain severity (p < 0.0001), and better Ntx-12 scores (p < 0.0001) compared with controls. Ketotifen was well tolerated and improved quality of sleep and appetite (p < 0.0001), addressing additional patient-reported challenges.
This trial indicates that ketotifen may offer a promising approach for preventing OIPN. Larger placebo-controlled, double-blind, multicenter trials are needed to confirm these findings.
NCT05624138.
1-11-2022.
36030/11/22.