Chemotherapy-induced neuropathy and pain in pediatric oncology patients: impact of combination therapies.

Chemotherapy-induced peripheral neuropathy (CIPN) and associated pain are prevalent adverse effects of pediatric cancer treatment, significantly affecting the patient's quality of life. Their impact and risk factors have yet to be assessed in our country. This study aimed to assess the prevalence and clinical characteristics of CIPN, as well as to explore associations with patient- and treatment-related variables, within a cohort of Argentinean pediatric oncology patients. Sixty-six patients diagnosed with malignant hematopoietic tumors and receiving the neurotoxic agent vincristine were included in this observational study. Variables analyzed included age, gender, anthropometric measurements, tumor type, chemotherapy treatment, development of pain and other symptoms, severity, and analgesic treatment. The study population consisted of 39 boys and 27 girls. Most patients received two or three neurotoxic drugs. Symptoms consistent with CIPN were identified in 15 children, reflecting a prevalence of 23%. The main symptom was pain in the lower limbs, with some patients reporting jaw or generalized body pain. Pain was categorized as moderate or severe in 60% and 27% of cases, respectively. NSAIDs, anticonvulsants, and/or opioids were prescribed. Among the patient- and treatment-related variables analyzed as potential risk factors, the use of vincristine in conjunction with cytarabine and the administration of a higher number of neurotoxic drugs demonstrated significant association with the development of CIPN. CONCLUSIONS: Combination therapy stands out as a risk factor for clinical CIPN. The high prevalence of moderate/severe pain underscores the importance of close vigilance given its potential to compromise the patient's overall well-being. WHAT IS KNOWN: • Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent adverse effect and dose-limiting factor in pediatric cancer treatment. • Prevalence varies among regions and risk factors are still under study. WHAT IS NEW: • Prevalence of symptomatic CIPN is 23% among pediatric patients undergoing treatment for hematopoietic tumors in a referral hospital in Argentina. Most patients report moderate or severe pain. • Combining vincristine with cytarabine and using a higher number of neurotoxic drugs in combination therapies exhibit significant association with the development of CIPN-related symptoms.

Rosuvastatin Synergistically Enhances the Antinociceptive Efficacy of Duloxetine in Paclitaxel-Induced Neuropathic Pain in Mice.

Paclitaxel, a widely used cancer chemotherapeutic agent, has high incidence of neurotoxicity associated with the production of neuropathic pain, for which only duloxetine has shown significant but moderate analgesic effect. Since statins, classically used to reduce hypercholesterolemia, have shown antinociceptive effect in preclinical studies on neuropathic pain, we studied whether the antinociceptive efficacy of duloxetine could be synergistically potentiated by rosuvastatin in a model of paclitaxel-induced neuropathy in mice. The astrocytic and microglial responses in the spinal cord of paclitaxel-treated mice were also assessed by measuring GFAP and CD11b proteins, respectively. Paclitaxel treatment did not impair motor coordination and balance in rotarod testing. Rosuvastatin, duloxetine, and the rosuvastatin/duloxetine combination (combined at equieffective doses) dose-dependently decreased mechanical allodynia (ED30, von Frey testing) and thermal hyperalgesia (ED50, hot plate testing) in paclitaxel-treated mice. Isobolographic analysis showed a superadditive interaction for rosuvastatin and duloxetine, as both the ED30 and ED50 for the rosuvastatin/duloxetine combination contained only a quarter of each drug compared to the individual drugs. The rosuvastatin/duloxetine combination reversed paclitaxel-induced GFAP overexpression, indicating that such effects might depend in part on astrocyte inactivation. Results suggest that statins could be useful in synergistically enhancing the efficacy of duloxetine in some chemotherapy-induced neuropathic conditions.