Efficacy of Duloxetine on electrodiagnostic findings of Paclitaxel-induced peripheral neuropathy, does it have a prophylactic effect? A randomized clinical trial

Abstract

This study aimed to evaluate the efficacy of Duloxetine on electrodiagnostic findings of Paclitaxel-induced peripheral neuropathy in patients with breast cancer. This randomized, double-blind clinical trial was conducted on 40 patients with breast cancer who received Paclitaxel as their first chemotherapy session. All the patients were randomly allocated into two groups, intervention (20 subjects) and placebo (20 subjects). The intervention group received 30 mg duloxetine/day in the first week, followed by 60 mg (twice daily) until 8 weeks. The patient neurotoxicity questionnaire (PNQ) was used to evaluate the severity of neuropathy. Nerve conduction study was also performed. The evaluations were performed at the baseline and 8 weeks after the treatment. Out of 20 subjects in the placebo group, 10 (50%) patients had neurotoxicity (two milds, three moderate, four severe, and one incapacitated), according to PNQ. However, in the duloxetine group, two patients had mild neurotoxicity (P = 0.03). Significant differences between groups related to the mean of Median Sensory Latency (P <0.001), Median Motor Latency (P < 0.001), and Median Motor velocity (P = 0.001) were reported. However, the relative risk of polyneuropathy between the two groups (relative risk: 1) was not significant. Regarding the results, duloxetine could be an effective treatment for preventing paclitaxel-induced peripheral neuropathy in patients with breast cancer, and an electrodiagnostic study confirmed this effect.

Duloxetine prevents bortezomib and paclitaxel large-fiber chemotherapy-induced peripheral neuropathy (LF-CIPN) in sprague dawley rats

“…Our finding that Duloxetine prevents the elevation of CPT caused by Bortezomib and Paclitaxel in the rat, supports the limited clinical observations suggesting that Duloxetine may be able to attenuate LF-CIPN, 13,25 as well as the need for well-powered studies of the effects of Duloxetine in patients with LF-CIPN. 25,28 Our study also provides a preclinical model that can be used to evaluate large-fiber function in rats being treated with other classes of chemotherapy drugs, and other candidate treatments for large-fiber CIPN, to precede the time consuming and costly process of evaluating the clinical efficacy and safety of drugs for the prevention and treatment of CIPN in clinical studies.…”

“…Clinical evidence that Duloxetine can be used to treat large-fiber peripheral neuropathy in oncology patients with CIPN is, at present, extremely limited. 13,24,25 In the present study, for the first time we have developed two preclinical models of LF-CIPN, one induced by Bortezomib and the other by Paclitaxel, to allow us to test the hypothesis that Duloxetine, the only drug currently recommended by the American Society of Clinical Oncology (ASCO), for the treatment of small-fiber painful CIPN, also attenuates LF-CIPN.…”

“…12 In some studies of the treatment of painful CIPN with Duloxetine, it was noted that Duloxetine also appeared to improve sensory modalities associated with large-fiber function. [13][14][15] Since there are currently limited pre-clinical models that allow the selective study of large-fiber neuropathy. 16,17 to evaluate candidate treatments for CIPN we used the Current Perception Threshold (CPT) tail reflex, elicited by high frequency electrical stimulation, 18 to evaluate changes in large-fiber function in rats treated with two neurotoxic chemotherapy agents that are known to induce LF-CIPN in oncology patients, Bortezomib 19,20 and Paclitaxel, 13,21 and their response to treatment with Duloxetine.…”

“…[13][14][15] Since there are currently limited pre-clinical models that allow the selective study of large-fiber neuropathy. 16,17 to evaluate candidate treatments for CIPN we used the Current Perception Threshold (CPT) tail reflex, elicited by high frequency electrical stimulation, 18 to evaluate changes in large-fiber function in rats treated with two neurotoxic chemotherapy agents that are known to induce LF-CIPN in oncology patients, Bortezomib 19,20 and Paclitaxel, 13,21 and their response to treatment with Duloxetine. The CPT test has been used successfully in preclinical studies as a noninvasive method to study large and small fiber neuropathy induced by vibration.…”

“…12 In some studies of the treatment of painful CIPN with Duloxetine, it was noted that Duloxetine also appeared to improve sensory modalities associated with large-fiber function. 13–15…”