Effect of Acetyl-L-Carnitine on theIncidence and the Severity ofPaclitaxel- Induced Peripheral Neuropathy inCancer Patients

Abstract

Peripheral neuropathy is a general term indicating the malfunction of peripheral nerves due to various causes. Neuropathic pain is defined as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system”.These injuries arise from different pathological conditions leading to the development of neuropathic pain such as; chemotherapy-induced peripheral neuropathy (CIPN), paraneoplastic neuropathy, inherited-induced neuropathy, diabetic peripheral neuropathic pain and human immunodeficient virus (HIV)-associated sensory neuropathy. CIPN is a toxic neuropathy that results from the direct injury of the peripheral nervous system by the chemotherapeutic agent.CIPN frequently complicates the use of several classes of chemotherapeutic agents: taxanes (paclitaxel and docetaxel), platinum-based compounds (carboplatin, cisplatin, and oxaliplatin), vinca alkaloids (vincristine and vinblastine), epothilones (ixabepalone) and proteasome inhibitors. CIPN incidence range widely among various studies anywhere between 10% and 100%. Rates may be as high as 60–70% with taxanes agents frequently used as first and second-line treatment for several common malignancies. CIPN is dose limiting and have negative effects on quality of life and functional capacity. In addition, the onset of CIPN often results in reduced doses of chemotherapy, or discontinuation of therapy altogether, patients are unable to complete full or optimal treatment schedules, likely impacting cancer related outcomes in a negative way. Paclitaxel is a widely used chemotherapeutic agent derived from Pacific yew tree bark. It is indicated for the treatment of ovarian, breast, non-small cell lung carcinomas and Kaposi’s sarcoma. Paclitaxel works by disrupting microtubule polymerization, in turn preventing the cell from entering mitosis. Paclitaxel artificially stabilize the dynamic end bonds, essentially freezing disassembly, and in turn bring mitotic cell division to a halt. The most important dose-limiting side effect of paclitaxel is neurotoxicity. Paclitaxel-induced peripheral neuropathy (PIPN) is due to the inability of paclitaxel to differentiate between malignant and healthy cells