Paclitaxel is a microtubule-binding compound that is widely used as a chemotherapeutic in the treatment of common cancers, including breast and ovarian cancer. Paclitaxel binding along the length of microtubules stabilizes them and suppresses their dynamics, leading to mitotic arrest and apoptosis in dividing cells.
Why is paclitaxel treatment associated with neurotoxicity?
Because paclitaxel promotes microtubule assembly, neurotoxicity is one of its side effects. Clinical use of paclitaxel has led to peripheral neuropathy and this has been demonstrated to be dependent upon the dose administered, the duration of the infusion, and the schedule of administration.
What is the mechanism of action of paclitaxel?
Mechanism of action of paclitaxel. Paclitaxel targets microtubules. At high concentration, PTX causes mitotic arrest at G2/M phase whereas at low concentration, apoptosis is induced at G0 and G1/S phase either via Raf-1 kinase activation or p53/p21 depending on the dose concentration.
Does Taxol cause neurotoxicity?
Neurotoxicity, manifested primarily by a motor and sensory polyneuropathy, is the principal nonhematological side effect of Taxol. Available evidence suggests that Taxol produces a toxic effect involving either axons or ganglion cell bodies, or both, rather than a myelinopathy.
How do you prevent neurotoxicity from chemotherapy?
Several neuroprotective strategies including calcium and magnesium supplementation, and administration of glutathione, glutamine, acetyl-L-carnitine, and erythropoietin have been suggested to prevent chemotherapy-induced peripheral neuropathy without compromising the treatment effect; however, clinical data supporting …
What are the symptoms of neurotoxicity?
Symptoms may appear immediately after exposure or be delayed. They may include limb weakness or numbness; loss of memory, vision, and/or intellect; headache; cognitive and behavioral problems; and sexual dysfunction. Individuals with certain disorders may be especially vulnerable to neurotoxicants.
Does paclitaxel cause neuropathy?
Paclitaxel (Brand name Taxol) is widely used in the treatment of common cancers like breast, ovarian and lung cancer. Although highly effective in blocking tumor progression, paclitaxel also causes peripheral neuropathy as a side effect in 60-70% of chemotherapy patients.
What does paclitaxel treat?
Paclitaxel is a chemotherapy drug. It is a treatment for many different types of cancer. It is also called Taxol.
Why does paclitaxel need a filter?
To prevent hazards associated with intravenous (IV) administration which include the formation of microbubbles, microbiological contamination and particulate matter, the suppliers recommend that an in-line IV filter should be used during the infusion of the chemotherapeutic agent.
What natural resources are used to make paclitaxel?
Paclitaxel, the most well-known natural-source cancer drug in the United States, is derived from the bark of the Pacific yew tree (Taxus brevifolia) and is used in the treatment of breast, lung, and ovarian cancer, as well as Kaposi’s sarcoma.
Why are taxanes neurotoxic?
Taxanes also bind to mitochondrial β-tubulin, causing mitochondrial damage by opening the mitochondrial permeability transition pore (mPTP) and increasing calcium efflux. These events trigger cancer cell apoptosis and necrosis (Weaver, 2014).
Is paclitaxel neuropathy reversible?
In the Phase I trial, we noted a severe but reversible sensory polyneuropathy at doses of paclitaxel 725 mg/m2; and in 5 of 18 patients, transient motor weakness was observed, which led to the des- ignation of 825 mg/m2 as the Phase II dose (23). The neuropathy was reversible, although at varying rates.
Why is paclitaxel given weekly?
The rationale for dose-dense weekly paclitaxel in the treatment of breast cancer is that more frequent delivery of more moderate doses may achieve greater efficacy than larger doses given less often through more sustained exposure of dividing tumor cells to cytotoxic drugs.
How is neurotoxicity treated?
The treatment approach to neurotoxicity is elimination or reduction of the toxic substance and therapy to relieve symptoms or provide support. Treatment may also involve avoiding air, food and water pollutants.
Which chemo drugs are neurotoxic?
Urotoxic side effects on the kidneys and urinary bladder are a limiting factor in chemotherapy with oxazaphosphorine cytostatics such as cyclophosphamide and ifosfamide. Acrolein was found to be the causative factor which is spontaneously formed in the urine from the primary metabolites eliminated via the kidneys.
What is central neurotoxicity?
Central neurotoxicity ranges from acute toxicity such as aseptic meningitis, to delayed toxicities comprising cognitive deficits, hemiparesis, aphasia and progressive dementia.