PACLITAXEL is a complex semi-synthetic diterpin taxine
isolated from the bark of pacific yew tree
taxus bravifolia. It is mainly approved for the use In human
oncology for the treatment of
breast, ovarian, and lung cancers and Kaposi’s sarcoma.
Chemical structure
Paclitaxel is a white to off white crystalline powder with the empirical formula C47H51NO14 and a molecular weight of 853.9 D.
It is highly lipophilic, insoluble in water and melts at around 216-217° C.
Mechanism of action:-
Promotes polymerisation and stabilization of polymer micro tubule
Inhibition of normal dynamic reorganisation of micro tubule
Dysfunctioning of micro tubules due to over stabilization
arrest of mitosis
Pharmacokinetic:
The pharmacokinetic information is lacking in animals. In humans paclitaxel does not cross the blood brain barrier. It is largely excreted via biliary root with small a component of renal excretion.
Adverse effect:
1. Bone marrow depression (Neutropenia)
2. G.I. Disturbances
3. Hypers sensitivity reactions (Anaphylaxis, Urticaria)
4. Alopecia in dogs (90%)
5. Bleeding or bruising, pain and swelling at the site of injection
6. Pneumonia, lung fibrosis, pulmonary embolism
7. Arthralgia, myalgia
8. Convulsion, Dizziness ( Neurological disturbances)
9. Renal toxicity, Renal failure
10. Severe shortness of breath
Note: Dexamethasone is given prior to paclitaxel treatment to mitigates some
the side effects
Indications (For humans):
1. Paclitaxel in combination with cisplatin indicated as
first line and subsequent therapy of treatment
of advance carcinoma of ovary
2. Metastatic breast cancer
3. Paclitaxel in combination with cisplatin use in non small
cell lung cancer
4. Kaposi’s sarcoma
5. Investigation for use in treatment of several neoplasm
in veterinary medicine
Safety warnings:
1. Paclitaxel should be administered under the supervision of
physician experienced in cancer chemotherapeutic agents.
2. Anaphylaxis, sever hypersensitivity, dyspnoea, hypotension,
angioedema have occurred in 2-4% of patient receiving
paclitaxel.
3. Pre-medication with steroids, anti-histaminic, H2 blockers
should be given.
4. Paclitaxel should not be less than 55-70%.
5. It is recommended to perform frequent blood count of
patient receiving paclitaxel.
Subcutaneous administration of paclitaxel in dogs with cancer: A preliminary study
Intravenous paclitaxel has been underused in dogs due to severe and acute hypersensitivity reactions. Subcutaneous (SC) administration of paclitaxel and its safety are unknown.
In this preliminary study, SC administration of paclitaxel was evaluated for hypersensitivity reactions and toxicity in 21 dogs with advanced cancer.
Dogs received 1 to 5 paclitaxel doses, ranging from 85 to 170 mg/m2, SC every 14 or 21 days.
A total of 40 paclitaxel doses were administered and none of the 21 dogs developed systemic or acute local hypersensitivity reactions. Severe skin lesions at the injection site developed in 2 dogs after the 4th injection at the same location.
Grade 4 neutropenia was observed in 50% of the dogs 5 days after the first treatment at 115 mg/m2 (n = 14).
Two animals developed Grade 5 diarrhea and died likely due to hemodynamic failure or sepsis. Paclitaxel can be administered SC in dogs with no hypersensitivity reaction.
Dose:
For Dogs – 170 mg/m2 (maximum tolerable dose) IV infusion
²
Surface area = Body weight⁰∙⁶⁷ × K/10⁴
Where surface area is given in square meters (m²) and body
weight in kilograms. For dogs, K is constant with value of 10.1
Overdose:
There is no known antidote for paclitaxel
overdosage. Only symptomatic treatment
should be done.
Presentation:
30mg/5ml, 100mg/16.7ml, and
260mg/43.4ml vials individually
packaged in a carton.
