Chemotherapy drugs are center point of treatment for childhood cancer. There are many classes of chemotherapy drugs available. Microtubules, which are an integral component of the cytoskeleton, play important roles in a variety of cellular functions including mitosis, cellular transport, maintenance of cell shape, polarity, and cell signaling. Traditional tubulin inhibitors include the vinca alkaloids, which are microtubule destabilizing agents, and the taxanes. New tubulin inhibitors, such as eribulin, that both bind directly to the microtubules and induce tubulin aggregates. Vincristine got FDA approval for use in cancer therapy in 1963. It is one of the oldest drug available for the treatment of malignancy.

Vinca Alkaloids

Obtained from periwinkle plant (Vinca Rosea)

• Vincristine
• Vinblastine
• Vindesine
• Vinorelbine

The vinca alkaloids exert their cytotoxic effect by binding to tubulin, a dimeric protein that polymerizes to form microtubules. The resulting disruption of the intracellular microtubular system interferes with a number of vital cell functions, including mitosis, maintenance of the cytostructure, membrane trafficking, and transmission of receptor signals, and transport of p53 to the nucleus. The cytotoxic effect is related to inhibit mitotic spindle formation, causing metaphase arrest during mitosis.

Mechanism of Action of Vincristine

• Microtubule binding
• Inhibition of microtubule polymerization
• Disruption of mitotic spindle formation
• Cell cycle arrest
• Induction of apoptosis
• selectively targets rapidly dividing cells

Why VCR given maximum 2 mg/dose? The standard dose for vincristine is 1 to 2 mg/m², administered every 1 to 3 weeks. For infants younger than or equal to 1 year of age, vincristine dose is scaled to body weight (0.03 to 0.05 mg/kg) or doses determined by infant dosing. Many regimens limit the total single dose of vincristine to 2 mg on the basis of reports of increased neurotoxicity at doses above 2 mg, especially on the weekly schedule. [Pizzo and Poplacks 7th]

Hepatic metabolism and biliary excretion are the principal routes for elimination of the vinca alkaloids.

Infants and young children have a larger body surface area relative to their weight. A study comparing vincristine dosing based on body surface area (1.5 mg/m²) versus body weight (0.05 mg/kg) found that dosing by body surface area resulted in higher drug levels in the body. This means that the body surface area method leads to greater drug exposure.

Dosage modifications of the vinca alkaloids are generally recommended in infants and in patients with delayed biliary excretion as evidenced by an elevated direct bilirubin.

Indications of Using Vincristine

1. ALL
2. Burkitt lymphoma
3. B-cell ALL
4. lymphoid blast crisis of chronic myeloid leukemia
5. neuroblastoma
6. Rhabdomyosarcoma
7. Wilms tumor
8. Hodgkin and non-Hodgkin lymphomas
9. CNS Tumor

Price in Bangladesh

Bangladeshi Pharmaceutical company such as Beacon Pharma. Drug International, Healthcare etc manufactures vincristine. It is available in 1mg/ml and 2mg/2ml formulation. Although 1mg/ml is rarely available in Market.

1mg/ml Price: 350 Tk

2 mg/2ml Price: 580 Tk

Toxicity of Vincristine

Neurotoxicity is the dose-limiting toxicity of vincristine. It is related to the cumulative dose and occurs more commonly on a weekly schedule. peripheral sensory and motor neuropathy include loss of deep tendon reflexes, neuropathic pain (muscular cramping, jaw pain), paresthesia’s, and wrist and foot drop. Autonomic nerve involvement may be responsible for constipation, paralytic ileus, and urinary retention. alopecia, inappropriate antidiuretic hormone syndrome, seizures, and orthostatic hypotension. Nausea and vomiting and myelosuppression are rarely encountered. Vincristine can increase the platelet count.

Myelosuppression is the dose-limiting toxic effect of vinblastine and vinorelbine. Vinblastine also frequently causes mucositis. Neurotoxicity with vinblastine is minimal and is less prominent with vinorelbine than with vincristine.

Vinca alkaloids are vesicants; extreme care must be taken to avoid extravasation during their administration.

1. Paralytic ileus leading to Constipation
2. Peripheral neuropathy
3. Extravasation causes local tissue injury and necrosis (Rx: Hot compression)
4. Jaw pain
5. SIADH

Accidental Intrathecal administration of VCR causes severe neurotoxicity which ultimate fatal outcome. So it should not be given in same days with IT MTX and Cytarabine therapy. Also VCR and IT should not be given in the same place.

Precaution:

Vincristine should be infused as a rapid push over 1 minute in a side port of a free-flowing IV line to avoid extravasation. IV cannula should be done before giving vincristine and vinca alkaloids. 

 If extravasation occurs

          – Infusion should be discontinued immediately

          – Application of warm compression

          – Elevation of the extremity

          – Local application- Hyaluronidase

Reference and Further reading:

Vincristine NCBI-NLM

Oncovin US Drug Name

Vincristine Drugs.com

Thanks

Here is a quick link to previous topics.

Chemotherapy drugs: Things you need to know

Chemotherapy Drugs for Childhood Cancer Part 2: Basics

Chemotherapy Drugs for Childhood Cancer Part 3 Basics

Chemotherapy Drugs for Childhood Cancer Part 4 Basics

Chemotherapy Drugs Cyclophosphamide Cisplatin Carboplatin