Duloxetine ameliorates oxaliplatin-induced peripheral neuropathy

Presented by

Dr Jeffrey Chi, Northwell Health Cancer Institute, NY, USA

Conference

ASCO GI 2021

Duloxetine resulted in a clinically significant improvement in peripheral neuropathy (PN) induced by oxaliplatin, with a manageable toxicity profile in this retrospective study. Additionally, duloxetine also improved depression and pain score. However, a prospective study should be conducted to conclude on efficacy and caution must be taken about duloxetine and other drugs interaction.

Dr Jeffrey Chi (Northwell Health Cancer Institute, NY, USA) presented the study, which included patients with gastrointestinal cancers [colorectal (CRC), pancreatic (PC), and gastric (GC)] receiving oxaliplatin-based chemotherapy regimens from November 2016 to November 2019 [1].

Duloxetine is a second-generation selective serotonin and norepinephrine reuptake inhibitor (SNRI) used for the treatment of depression, anxiety, PN associated with diabetes, or ongoing pain due to medical conditions such as fibromyalgia. In this retrospective study, the researchers evaluated the role of duloxetine in reduction of oxaliplatin-induced neuropathy. Neurological evaluations were performed at baseline and every 4 weeks thereafter according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Oral duloxetine was given at 30 mg once daily and if tolerated after 3 days, was escalated to 60 mg once daily. Data was classified by PN grade (G0 being absence of PN, to G3 being severe PN).

A total of 53 patients with gastrointestinal cancer (CRC: 40%, PC: 30%, GC: 10%, others: 10%; median age 53 years) received duloxetine for oxaliplatin-induced PN. At 4 weeks into the study, 3/53 (6%) patients improved from G3 PN to G2, 6/53 (11%) from G3 to G1, and 28/53 (52.8%) from G2 to G1, 14/53 (26%) and 2/53 (4%) had stable G3 and G2 PN, respectively. At 8 weeks of duloxetine, 10/53 (19%) of patients improved from G3 to G2, 3/53 (6%) from G2 to G1, 23/53 (43%) from G1 to G0, while 11/53 (21%), 2/53 (4%), and 4/53 (8%) remained stable at G1, G2, and G3, respectively. Overall, duloxetine resulted in a response rate of 89% and stable PN in 11%. In addition to PN, duloxetine helped in improving depression in 50% of these patients and decreased the pain score in an additional 23%.

Overall, duloxetine was well-tolerated with majority of toxicities in G1-2 grade: dizziness (15%), drowsiness (11%), sexual side effects (11%), dry mouth (11%), insomnia (8%), headache (8%). Only 5 patients had to stop duloxetine due to G3 drowsiness, insomnia, dry mouth, and headache.

Dr Chi concluded by pointing to the need for a prospective randomised trial to study the effectiveness of duloxetine in treating oxaliplatin-induced PN. Moreover, cost effectiveness of duloxetine in concurrently improving PN, depression, and pain needs to be studied as well.

Chi J, et al. Duloxetine (DL) in treatment of oxaliplatin-induced peripheral neuropathy (PN). ASCO Gastrointestinal Cancers Symposium 2021, 15-17 January. Abstract 195.

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