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Docetaxel

Indication

Locally advanced or metastatic breast cancer & non-small cell lung cancer (NSCLC) after failure of prior chemotherapy. Treatment of advanced gastric adenocarcinoma, adenocarcinoma of the gastroesophageal junction & locally advanced squamous cell carcinoma of the head & neck (SCCHN) in combination w/ cisplatin & fluorouracil. Treatment of androgen independent (hormone refractory) metastatic prostate cancer in combination w/ prednisone.

Dosage / Direction For Use

Given by IV infusion in glucose 5% or sodium chloride 0.9% at conc not >0.74 mg/mL over 1 hr. Premedication: Dexamethasone 16 mg daily for 3 days starting 1 day before taking Docetaxel. Locally advanced or metastatic breast cancer As single agent: 100 mg/m2; in combination w/ doxorubicin: 75 mg/m2; in combination w/ trastuzumab: 100 mg/m2 every 3 wk, w/ trastuzumab administered wkly; in combination w/ capecitabine: 75 mg/m2 every 3 wk combined w/ capecitabine at 1,250 mg/m2 bid (w/in 30 min after a meal) for 2 wk followed by a wk rest period. NSCLC 75 mg/m2 once every 3 wk, for both 1st-line combination therapy & monotherapy after failure of previous chemotherapy. Gastric adenocarcinoma 75 mg/m2 given before cisplatin & fluorouracil, repeated every 3 wk. Induction treatment of head & neck cancer 75 mg/m2 given before cisplatin & fluorouracil every 3 wk for 3 cycles, followed by chemoradiotherapy or for 4 cycles when followed by radiotherapy alone. Prostate cancer 75 mg/m2 once every 3 wk w/ prednisone or prednisolone 5 mg orally bid given continuously.

Overdosage

The primary anticipated complications of overdose would consist of bone marrow suppression, peripheral neurotoxicity and mucositis. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose.

Administration

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Contraindication

Docetaxel is contraindicated in patients who have a history of hypersensitivity reactions to the active ingredient or to any of the excipients (Polysorbate 80, Ethanol 96% and Citric acid monohydrate).Docetaxel should not be used in patients with baseline neutrophil count of <1,500 cells/mm3 and in patients with severe liver impairment.

Special Precaution

Before each treatment, test blood for enough blood cells & sufficient liver function. Patient may experience fever or infections in case of WBC disturbance. Patients in whom alcohol intake should be avoided or minimized. May impair ability to drive or use machinery. Pregnancy & lactation.

Adverse Reactions

Neutropenia, anemia and skin reactions are common with Docetaxel and may be severe. Fluid retention, resulting in oedema, ascites, pleural and pericardial effusion, and weight gain, is also common, and may be cumulative; premedication with a corticosteroid can reduce fluid retention as well as the severity of hypersensitivity reactions.Effects on the eyes: Excessive tear formation (epiphora) severe enough to interfere with reading and driving has been reported. Very rare cases of transient visual disturbances such as flashing lights and scotomata have occurred during Docetaxel infusion, and in association with hypersensitivity reactions.Effects on the gastrointestinal tract: Ischemic colitis has occurred in patients treated with Docetaxel.Effects on the heart: Heart failure has been reported in patients given Docetaxel with other cytotoxic drugs especially trastuzumab, and particularly after anthracycline-containing therapy.Effects on the skin and nails: Palmar-plantar erythrodysesthesia syndrome has been reported with the use of Docetaxel. Cases of radiation recall dermatitis associated with Docetaxel have also been reported. There is further report of recall dermatitis at sites previously treated with a laser.A hyperpigmented eruption developed in a patient at the site of Docetaxel injection after insufficient venous flushing.

Drug Interaction

Metabolism of Docetaxel may be modified by the concomitant administration of compounds which induce, inhibit or are metabolized by (and thus inhibit the enzyme competitively) cytochrome P450-3A such as: cyclosporine, terfenadine, ketoconazole, erythromycin and troleandomycin. As a result, caution should be exercised when treating patients with these medicinal products as concomitant therapy since there is a potential for significant interaction.

Storage

Store in a refrigerator (2°C to 8°C). Protect from light.The infusion solution, if stored below 25°C, is stable for 8 hours in PE infusion bottle or for 6 hours in PP infusion bag (including the one hour IV infusion administration). When prepared as recommended, in non-PVC bags and stored between 2-8°C, it is stable up to 48 hours.

Description

Each mL contains Docetaxel 20 mg.

Action

Pharmacology: Pharmacodynamics: Docetaxel is an antineoplastic agent which acts by promoting the assembly of tubulin into stable microtubules and inhibits their disassembly which leads to a marked decrease of free tubulin. The binding of Docetaxel to microtubules does not alter the number of protofilaments. Docetaxel has been shown in vitro to disrupt the microtubular network in cells which is essential for vital mitotic and interphase cellular functions.Pharmacokinetics: In intravenous dosage, Docetaxel is rapidly distributed to body tissues. Docetaxel is more than 95% bound to plasma proteins. it is extensively metabolized via hepatic cytochrome P450 isoenzyme CYP3A4 and excreted chiefly in the feces as metabolites. Only about 6% of a dose is excreted in urine. The terminal elimination half-life is about 11 hours. Clearance is reduced in hepatic impairment