Vinblastine

Vinblastine is a vinca alkaloid derived from the periwinkle plant (Vinca minor).

CHEMICAL STRUCTURE AND PHARMACOKINETIC PROPERTIES

Vinblastine is a chemical analogue of vincristine. Vinblastine is composed of a vindoline ring linked to a catharanthine ring by means of carbon-carbon bonds. A methyl group is bound to the vindoline ring.

The pharmacokinetic properties of vinblastine are consistent with a three-compartment model: extensive distribution in extravasal compartments, a high clearance rate and a long terminal half-life (with a consequent prolonged elimination).

Following intravenous administration, vinblastine binds rapidly to plasma proteins, red blood cells, leukocytes and platelets. Vinblastine does not cross the blood-brain barrier.

Vinblastine is metabolised in the liver by the cytochrome P-450; the  major route of excretion is the biliary system (7 days), while a small amount is excreted in the urine for 7 days. In serum samples vinblastine is no longer detectable after 7 days.

MECHANISM OF ACTION

Vinblastine is a phase-specific agent, which acts during the M phase (mitosis) of the cell cycle. It can also be defined as an antimicrotubular agent. The mechanism of action of vinblastine is identical to that of vincristine.

MECHANISM OF RESISTANCE

Resistance to vinblastine is caused by the expression of glycoprotein P-170, which results in extrusion of the chemotherapeutic agent from the neoplastic cell, and by modification of the target, which is tubulin.

CLINICAL INDICATIONS AND DOSE

The main indication for vinblastine is the treatment of mast cell tumours. Other tumours that may respond to this drug are lymphomas and leukaemias.

In the dog the dose of vinblastine is 2-2.5 mg/m_² by rapid intravenous bolus injection every 1-3 weeks. As a single agent it can be administered at the dose of 3.5 mg/m_²  intravenously every 14 days. In the cat the dose of vinblastine is 2 mg/m_² by rapid intravenous bolus injection every 1-3 weeks.

TOXICITY

The adverse events of vinblastine involve various organs and apparatuses:

• bone marrow: non-cumulative myelosuppression (neutropenia);
• gastrointestinal apparatus: generally mild and self-limiting. The toxicity is greater in patients with existing gastrointestinal disorders;
• skin: vinblastine is a vasosclerosing agent. In the case of accidental extravasation the same measures as those used for extravasation of vincristine must be employed.

Suggested readings

1. Bailey DB, Rassnick KM, Kristal O et al: Phase I dose escalation of single-agent vinblastine in dogs. J Vet Intern Med. 2008; 22: 1397-402.
2. Chun R, Garrett LD, Vail DM: Cancer chemotherapy. In: Withrow & MacEwen’s Small Animal Clinical Oncology, Withrow SJ and Vail DM (eds), Saunders Elevier, 2007: 163-192.
3. Golden DL, Langston VC. Uses of vincristine and vinblastine in dogs and cats.  J Am Vet Med Assoc. 1988; 193: 1114-7.
4. Knobloch A, Mohring SA, Eberle N, et al: Drug residues in serum of dogs receiving anticancer chemotherapy. J Vet Intern Med. 2010; 24: 379-83.
5. Knobloch A, Mohring SA, Eberle N, et al: Cytotoxic drug residues in urine of dogs receiving anticancer chemotherapy. J Vet Intern Med. 2010; 24: 384-90.
6. Marconato L: Agenti alchilanti. In: Principi di chemioterapia in oncologia, Marconato (ed), Poletto Editore, 2009: 79-92.
7. Rassnick KM, Bailey DB, Flory AB et al: Efficacy of vinblastine for treatment of canine mast cell tumors. J Vet Intern Med. 2008; 22: 1390-6.
8. Vickery KR, Wilson H, Vail DM, Thamm DH: Dose-escalating vinblastine for the treatment of canine mast cell tumour. Vet Comp Oncol. 2008; 6: 111-9.