600  Paclitaxel

Paclitaxel
Pak’li tax’el
Trade and other names: Paccal Vet-CA1 (veterinary formulation), Abraxane and
Taxol (human formulations)
Functional classification: Anticancer agent, Antineoplastic

Pharmacology and Mechanism of Action

Paclitaxel is an anticancer agent used in dogs for some neoplasms. It is a natural
product derived from the western yew tree and obtained via a semisynthetic process
from Taxus baccata. Paclitaxel is in the class of drugs called taxanes, which are
tubulin-protein active drugs for treating cancer.
From paclitaxel, there is also the semisynthetic drug docetaxel. These drugs differ
from vincristine and vinblastine. They bind to a different site on the tubulin protein
and promote, rather than inhibit, mitotic spindle formation. The mitotic spindles
formed are aberrant and disrupt the mitotic phase of the cell cycle. These drugs pro-
mote the assembly of microtubules from tubulin dimers and stabilize microtubules by
preventing depolymerization. This stability results in the inhibition of the normal
dynamic reorganization of the microtubule network that is essential for vital inter-
phase and mitotic cellular functions. These drugs may be active in other parts of
the cell cycle, as they induce abnormal microtubules throughout the cell cycle and
multiple asters of microtubules during mitosis.
In dogs, pharmacokinetic studies demonstrate that the terminal half-life may be as
long as 12 hours in some dogs, with high volume of distribution.
Indications and Clinical Uses
Paclitaxel and the related drug docetaxel are used for a variety of cancers in people
(e.g., breast cancer) as part of a chemotherapy regimen. In dogs, paclitaxel has been
used for mammary carcinoma and squamous cell carcinoma, and perhaps other tumors.
Paclitaxel also has been used in dogs for mast cell tumors (MCTs).
Precautionary Information
Adverse Reactions and Side Effects
The human formulation, which contains Cremophor EL (polyoxyethylated castor
oil) as a carrier vehicle, can cause severe anaphylactoid reactions in dogs and
should be avoided. Adverse effects in dogs from the veterinary form are primarily
related to bone marrow suppression. The most severe neutropenia usually occurs
in 5-7 days after administration. Thrombocytopenia, vomiting, and constipation
also are possible. As with many other anticancer agents, vomiting, diarrhea, and
nausea are common.
Do not use in dogs that are pregnant, lactating, or intended for breeding.
Paclitaxel is a teratogen and can affect female and male fertility. Laboratory studies
in the rat have shown reduced fertility, embryotoxicity, teratogenicity, and maternal
toxicity.
Contraindications and Precautions
Because this is an anticancer agent, standard precautions should be applied when
using this agent in animals. These precautions include following manufacturer’s
recommendations for safe handling of the vials and syringes, and disposing of
infusion supplies.