Pacitaxel Treatment

Paclitaxel is given as a shot to the vein (intraveneously). A licensed physician supervises administraction, although a nurse or technician often sticks the tube in the blood vessel. It takes a while for the drug to enter the circulatory system, so the patient is hooked up for over 30 minutes. The time for treatment varies considerably for different patients and different cancers. Sometimes it takes hours to administer the Paclitaxel.

It is common for patients to be "premedicated" with dexamethasone. This is a steroid that acts as an anti-inflammatory and can help stop the patient from getting nauseous during administration of the Paclitaxel.

Because Taxol is a toxin, healthcare providers use gloves. Topical exposures have resulted in tingling, burning and redness.

The website uptodate.com reports these typical dosages

Ovarian carcinoma:

I.V.: 135-175 mg/m2 over 3 hours every 3 weeks or
135 mg/m2 over 24 hours every 3 weeks or
50-80 mg/m2 over 1-3 hours weekly or
1.4-4 mg/m2/day continuous infusion for 14 days every 4 weeks
Intraperitoneal (unlabeled route): 60 mg/m2 on day 8 of a 21-day treatment cycle for 6 cycles, in combination with I.V. paclitaxel and intraperitoneal cisplatin. Note: Administration of intraperitoneal paclitaxel should include the standard paclitaxel premedication regimen.

According to an article in the International Journal of Women's Health, "no ideal dosing strategy for paclitaxel exists in ovarian cancer". Attempts to establish an ideal regimen have produced mixed results.

Metastatic breast cancer:

I.V.: 175-250 mg/m2 over 3 hours every 3 weeks or
50-80 mg/m2 weekly or
1.4-4 mg/m2/day continuous infusion for 14 days every 4 weeks

Nonsmall cell lung carcinoma:

I.V.: 135 mg/m2 over 24 hours every 3 weeks

AIDS-related Kaposi's sarcoma:

I.V.: 135 mg/m2 over 3 hours every 3 weeks
or 100 mg/m2 over 3 hours every 2 weeks

Clinical trials resulted in unprecedented success in treating ovarian cancer. Taxol had become a miracle drug. The sudden demand for Yew bark led to illegal “Taxus Rustling” and legal cottage industries. These new jobs were seen locally as replacements to the declining timber industry. It was obvious to everyone that the demand was unsustainable. Although complete synthesis of Taxol was successful, it was not practical. A process that creates the precursors by plant cell fermentation is now used to produce the world’s supply of Taxol. By 1995, all dependence upon the Pacific Yew was eliminated.

The popularity of this effective drug made it a “blockbuster”. Bristol Meyers Squibb sales of their branded product, Taxol, were almost $1.6 billion in 2000. There were numerous patents for various applications, which began to run out in the late 1990’s. The generic equivalent, Onxol, came on the market in 2000 and accounted for 17% of Ivax total generic sales in 2001.

Administration

Paclitaxel is administered as part of a liquid solution. It's dissolved in polyoxyethylated castor oil (often a branded solvent called Cremophor) and ethanol. Strictly speaking, Taxol refers to the solution rather than the Paclitaxel itself. The side effects of Paclitaxel, like those of many agents, is due to systematic administration - the drug travels through the bloodstream to the whole body and it stops fast-mulitplying cells in the hair follicles and intestines (resulting in hair loss and nausea.)

Patients taking anticonvulsant medicines can tolerate a higher dosage of Paclitaxel. If you take phenytoin or phenobarbital your liver might be better able to eliminate the toxic chemotherapy drug. That is one hypothesis for why this is true.

Taxol has another downside that other chemo agents don't have in that the cremophor and alcohol are toxic. It also does not work well with a range of other medicines. Consult your healthcare provider before starting any new medicine, including over-the-counter products.

Innovators are trying to improve chemotherapy delivery with materials science. Small spheries with pacltaxel enclosed are one viable option researchers are looking at. More on selivery.

Elimination

Paclitaxel exits the body mostly through the feces. Less than 20% comes out in the urine. Some is broken down by the liver. For a 3-hour administration, the half-life is under 24 hours. For a 24-hour infusion administration, the half-life is a couple days.

Side Effects of This Drug

Resources

Related: A phase I/II study of sepantronium bromide (YM155, survivin suppressor) with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer

 

From the forest comes a medicine...
paclitaxel molecule
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