Alkaloid isolated from periwinkle.
Effects the mitotic spindle causing cell cycle arrest during metaphase.
Induces cell cycle specific cytotoxicity by binding to tubulin during active mitosis, resulting in microtubule depolymerization and metaphase arrest, leading to apoptosis.
Cell-cycle specific agent whose activity is dependent on the duration of drug exposure.
Utilization limited by its short half life and dose limitation by neurotoxicity.
After intravenous administration undergoes rapid cellular uptake, extensive tissue blinding with a half-life of minutes with low levels of vincristine in the last.
Dose intensity is limited by peripheral and central nervous system neurotoxicity and begins at doses 1.4 mg per meter squared and is usually capped at a dose of 2 mg.
Intravenous agent with poor CNS penetration.
Used to treated acute lymphoblastic leukemia, Hodgkin’s disease and non-Hodgkin’s lymphoma, myeloma, Wilms tumor, neuroblastoma, breast-cancer, soft tissue sarcoma, and brain tumors in both adults and children.
Used in every protocol for childhood ALL, and for children with neuroblastoma, Wilms tumor’s, rhabdomyosarcoma, Ewing sarcoma, and retinoblastoma.
Exerts its cytotoxic effects by interfering with microtubule formation and mitotic spindle dynamics.
Leads to mitotic arrest and cell death.
Peripheral neuropathy can lead to impaired manual dexterity, balance, deep tendon reflex abnormalities and altered gait.
Side effects include abdominal cramps, constipation, alterations in taste, bruising, neurotoxicity, which may not be reversible.
Dose-limiting toxic effect is peripheral neuropathy with neuropathic pain and sensory and motor dysfunction.
Inadvertent intrathecal administration produces ascending myeloencephalopathy.
Inadvertent intrathecal administration causes distal lower extremity weakness, leg pain, loss of calcaneus reflex, autonomic dysfunction with urinary retention, symptoms of meningitis, respiratory failure and death.
Liposomal forms prolong circulation of active drug and allows passage of drug to tissues with fenestrated vasculature such as the bone marrow, lymph nodes, spleen, liver and solid tumor leading to first-order release kinetics with deposition of the drug over several days.
Has a narrow therapeutic index due to neuronal toxicity.
Approximately 25% of children and adults develop clinically significant vincristine induced peripheral neuropathy resulting in dose reduction or discontinuation of therapy.
Vincristine induced neuropathy associated with an inherited single nucleotide polymorphism in the promoter region of the CEP72 gene.