Effectiveness of duloxetine in treatment of painful chemotherapy-induced peripheral neuropathy: a systematic review
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect that can be dose limiting and affect patient quality of life. To date, the therapeutic options for CIPN are limited. We performed a systematic literature search of the PubMed and Scopus databases to assess the effectiveness of duloxetine in the treatment of pain in patients with CIPN. The search included randomized controlled trials, nonrandomized controlled trials, retrospective studies, and single-arm studies of duloxetine in treatment of CIPN. A descriptive analysis of the studies was performed. The PubMed database online search identified 41 publications, and a second database search through Scopus identified 29 publications. A total of 10 full-text articles were assessed for eligibility, with 5 articles excluded. Altogether, the included studies reported 431 patients with painful CIPN. An improvement in pain scores was the primary and/or secondary endpoint in the included studies. Pain was assessed by 6 different scores. Comparator drugs were used in 4 studies in our review. The comparator drug was placebo in 1 study only, and the remaining 3 studies used other antineurotoxicity therapy. The chemotherapeutic agents used in the studies were the following: paclitaxel (52.9%), oxaliplatin (39.7%), R-CHOP (rituximab, doxorubicin, vincristine, and cyclophosphamide; 3.30%), combined bortezomib-dexamethasone (1.89%), FOLFOX (folinic acid, fluorouracil, and oxaliplatin; 1.18%), and other taxanes (0.94%). From the descriptive analyses, and from the available data of relatively small sample sized studies, it can be concluded that despite the above limitations, duloxetine remains a useful therapeutic option for pain in CIPN patients, regardless of the type of chemotherapeutic agent used.
Accepted for publication November 20, 2018
Correspondence Wael Ibrahim, MD; dr.wael_ezzat@hotmail.com
Disclosures The authors report no disclosures/conflicts of interest.
©2018 Frontline Medical Communications
doi https://doi.org/10.12788/jcso.0436
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect that can be dose limiting and affect patient quality of life for prolonged time,1 with an overall incidence of about 38% in patients who are treated with multiple chemotherapeutic agents. 2
The most common antineoplastic agents causing peripheral neuropathy are oxaliplatin, cisplatin, taxanes, Vinca alkaloids, bortezomib, and thalidomide.3,8,9
Different components of the nervous system are targets of various chemotherapeutic agents, from dorsal root ganglion (DRG) cells to the distal axon. The DRG is the most vulnerable to neurotoxicity because it is less protected by the nervous system blood barrier, hence the predominance of sensory symptoms in CIPN.10 The pathogenesis of CIPN is not fully understood, and it is most probably multifaceted and not always related to the antineoplastic mechanism. Findings from experimental studies have shown an accumulation of chemotherapeutic compounds in the cell bodies of the DRG, resulting in decreased cellular metabolism and axoplasmic transport. Another proposed mechanism is the induction of apoptosis in sensory neuron of the posterior spinal ganglion after binding to DNA strands.7,11
Opioids had been used for managing pain in patients with cancer, but their addictive side effects limit use in the treatment of chronic pain,12 so several drugs called coanalgesics have been introduced as a treatment
The imbalance of 5HT and NE in the pain inhibitory pathways may contribute to the peripheral neuropathic pain.20 Duloxetine hydrochloride is a 5HT–NE reuptake inhibitor used to treat depression and generalized anxiety disorder.21 Duloxetine effect in decreasing pain transmission through increasing synaptic concentrations of NE and 5HT, which results in blocking input signals to the dorsal horn neurons in the spinal cord.12
Methods
We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA statement) guidelines during the preparation of this systematic review.22
Inclusion criteria
Trial or study type. Articles publishing findings from randomized controlled trials, nonrandomized controlled trials, retrospective studies, and single-arm studies of duloxetine in the treatment of CIPN were included in our review.
Intervention. The intervention was duloxetine with all doses, either administered alone or with other antineuropathic drugs.
Comparator. The comparator was placebo (control group) or other antineuropathic drugs or no control group.
Population. The population included cancer patients with painful CIPN.
Outcome. At least one of the following outcomes was used for pain assessment:
