effect of melatonin on paclitaxel-associated acute and chronic pain: a randomized, double-blind, placebo-controlled clinical trial

Background: taxane-induced pain is a disabling condition. this trial was conducted to assess the effects of melatonin on preventing paclitaxel-associated acute and chronic pain or decreasing its severity in patients with breast cancer. methods: this randomized, double-blind, placebo-controlled clinical trial was conducted on breast cancer women who received weekly paclitaxel (80 mg/m2) with or without trastuzumab after using doxorubicin + cyclophosphamide. the intervention group randomly received oral melatonin (10 mg/day) or placebo, which started from the first night of chemotherapy and continued through the planned 12 weeks of chemotherapy. the level of arthralgia-myalgia as acute pain was assessed every day in both groups using the brief pain inventory (bpi). the douleur neuropathique 4 questionnaire (dn4) and national cancer institute common terminology criteria for adverse events (nci-ctcae) version 5.0 were used to measure chemotherapy-induced peripheral neuropathy as chronic pain. results: seventeen patients were enrolled in each group randomly. the incidence of neuropathy according to a dn4 score ≥ 4 was significantly lower in the melatonin group versus the placebo group at week 12 compared to baseline (5 vs 11, p-value= 0.039). in addition, the mean neuropathy severity was significantly lower in the melatonin group over time (β= -0.051, p-value= 0.01). however, there were no significant differences in the mean worst and least pain scores over the twelve cycles of treatment between arms (p-value= 0.633 and 0.34, respectively). conclusion: co-administration of melatonin in women with breast cancer decreased the incidence of severe paclitaxel-associated neuropathy but melatonin was not effective against acute pain.