Effectiveness of duloxetine in treatment of painful chemotherapy-induced peripheral neuropathy: a systematic review

Abstract

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 CIPN has various clinical presentations – affecting the motor, sensory, and autonomic nerves – but the most common manifestations are numbness, tingling, and burning pain affecting the upper and lower extremities (the stocking-and-glove distribution).3-5 It can also lead to numerous negative effects on activities of daily living, functioning,6 leisure activities, dressing, household and work activities, going barefoot or wearing shoes, and driving. The incidence of CIPN is variable, depending on many factors such as type of chemotherapy, total dose, dose per cycle, infusion duration, and comorbidities as diabetes mellitus. 5-7 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 for CIPN, including antidepressants (tricyclic antidepressants, serotonin [5HT], and norepinephrine [NE] reuptake inhibitors), anticonvulsants (carbamazepine, and gabapentin), topical lidocaine patch, and topical gel.13 Duloxetine has been shown to be effective as a treatment option for