Risk Factors for Chemotherapy-Induced Peripheral Neuropathy Caused by Nanoparticle Albumin-Bound Paclitaxel in Advanced Breast Cancer

Abstract

Breast cancer (BC) is one of the most common malignancies affecting women and the leading cause of related mortality worldwide. An estimated 2260000 new cases of BC were diagnosed in 2020, which have seriously threatened the health. Paclitaxel (PTX), a natural product isolated from the bark of the pacific yew, has been found to be effective in treating advanced BC. Chemotherapy-induced peripheral neuropathy (CIPN), which refers to the damage to the peripheral nerves caused by exposure to a neurotoxic chemotherapeutic agent, is a common side effect affecting the patients undergoing PTX chemotherapy. Significant research efforts are needed to identify the various risk factors associated with CIPN. Here, a univariate analysis in BC patients with nanonab-PTX treatment was performed. The rate of CIPN in BC patients with albumin-bound paclitaxel (nab-PTX) for more than four weeks was significantly higher than that of patients with chemotherapy for less than four weeks. Moreover, the rate of CIPN in BC patients receiving nab-PTX first-line chemotherapy was remarkably higher than that in BC patients receiving paclitaxel as a sequence scheme. Taken together, chemotherapy cycles and the priority of nab-PTX-based chemotherapy can be considered the potential risk factors for CIPN induced by nab-PTX.

Natural Taxanes: From Plant Composition to Human Pharmacology and Toxicity

“…Due to the mechanism of action of paclitaxel or taxanes on microtubules, which results in the inhibition of the cell division cycle, in addition to tumour cells, organ systems containing rapidly dividing cells are most often affected, such as: the hematopoietic system and the development of myelosuppression, the neurological system and the development of neuropathy, the gastrointestinal system and the development of the upper and lower dyspepsia, diarrhoea and skin leading to alopecia. The incidence of adverse effects and symptoms of toxicity in the treatment of cancer patients with paclitaxel ranges from 70% to 83.6% [ 95 , 96 ]. Due to the frequent occurrence of adverse effects, which can limit the dosing schedule of paclitaxel, the effort is to find suitable combinations with other substances in order to reduce them.…”

“…The most common first manifestation of neurotoxicity is the development of paresthesis; then, as the symptoms of toxicity progress, sensory disorders, motor disorders, and autonomic nervous dysregulation occur. Primarily, the first symptoms occur on the distal parts of the limbs and progress proximally [ 96 ]. The emergence of this peripheral neuropathy is explained by the arrest of the growth of distal part of the axons of sensory neurons in the skin and proximal parts of the limbs, which causes the sensory symptoms of neurotoxicity described above [ 106 ].…”

“…The incidence of nab-paclitaxel toxicity is 70%, and 10% of patients experience a severe grade with significantly reduced quality of life. Symptoms begin to appear during the first cycle of administration and may persist for up to one year [ 96 ]. The incidence of taxane-induced neurotoxicity occurs in 13–62% of cases, with severe grade occurring in 5–10%.…”