Paclitaxel

Paclitaxel

Definition

Paclitaxel is a drug used to treat certain types of cancer. Paclitaxel is available under the trade name Taxol.

Purpose

Paclitaxel is an antineoplastic agent used to treat ovarian cancer , breast cancer , non-small cell lung carcinoma , and AIDS-related Kaposi's sarcoma .

Description

Paclitaxel was approved by the Food and Drug Administration (FDA) in 1992.

Paclitaxel is a naturally occurring compound originally extracted from the bark of the Pacific yew tree (Taxus brevifolia ). Due to high demand, paclitaxel is typically synthesized from the more abundant, naturally occurring compound 10-deacetyl baccatin III, which is extracted from the needles of yew plants. Paclitaxel belongs to a group of chemicals called taxoids. Docetaxel , a taxoid found in the English yew tree (Taxus baccata ), is similar to paclitaxel in terms of chemical structure and biological action.

Paclitaxel (and docetaxel) disrupt microtubule function, inhibiting cell replication. One of the roles of normal microtubules is to aid in the replication of cells, and Paclitaxel promotes the formation of microtubules that do not function properly, thus disrupting this function and inhibiting cell replication.

Paclitaxel is used in patients who have ovarian cancer carcinoma alone, and in combination with platinum-containing drugs such as cisplatin . Paclitaxel is also used to treat breast cancer that has recurred or progressed following treatment with other drugs. It is also used to treat non-small cell lung carcinoma in combination with cisplatin in cases where surgery or radiation is not possible.

Paclitaxel is also used to treat AIDS-related Kaposi's sarcoma.

Recommended dosage

There is no known antidote for paclitaxel overdose, so patients should be carefully monitored during treatment for toxicity.

Paclitaxel is administered intravenously once every three weeks. Blood tests may be necessary to ensure that the bone marrow is functioning adequately to continue treatment at the recommended interval.

All patients should be pretreated prior to paclitaxel administration with corticosteroids and antihistamines to help prevent adverse side effects. These side effects include severe hypersensitivity to paclitaxel.

Precautions

Paclitaxel should only be used under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Special caution should be taken to monitor the toxic effects of paclitaxel, especially suppression of bone marrow function and hypersensitivity reactions. Premedication to prevent hypersensitivity reactions is recommended. Minor to severe hypersensitivity reactions are frequent and may occur within a few minutes of the start of treatment. Severe hypersensitivity requires treatment to stop. Paclitaxel has a low therapeutic index. Certain complications will only be possible to manage if the necessary diagnostic and treatment resources are readily available.

Because paclitaxel is administered intravenously, and the site of infusion should be monitored for signs of inflammation.

Cardiac monitoring during paclitaxel administration is recommended in patients with a preexisting cardiac condition.

The occurrences of adverse effects of paclitaxel treatment in patients with significant liver dysfunction are more likely.

Paclitaxel should not be administered to patients who are known to have severe hypersensitivity to polyoxy 35 castor oil, which is a component of the treatment that helps dissolve the drug.

The safety of paclitaxel in children under 16 years of age has not been established.

Paclitaxel can cause harm to a fetus when administered to pregnant women. Only in life-threatening situations should this treatment be used during pregnancy. Women of childbearing age are advised not to become pregnant during treatment. Women should stop nursing before beginning treatment, due to the potential for serious adverse side effects in the nursing infants.

Side effects

Suppression of bone marrow function is the principal adverse side effect associated with paclitaxel treatment. Blood tests will allow a doctor to determine if there is adequate bone marrow function to begin or continue treatment. Hypersensitivity may also occur during treatment. Premedication is administered prior to treatment to help alleviate this side effect. Additional side effects, including fever , infection, nausea, vomiting, increase or decrease in blood pressure, diarrhea , weight loss , pain, and hair loss (alopecia ) may occur.

Interactions

When used in combination with cisplatin, paclitaxel should be administered first. Paclitaxel may increase the level of doxorubicin (a DNA interactive anticancer drug) in the blood when used in combination. Drugs that may alter the metabolism of paclitaxel such as cyclosporine (immunosuppressant), terfenadine (anti-fungal), ketoconazole (antifungal), erythomycin (antibacterial), and troleandomycin (antibacterial) should be used with caution due to the potential for interactions.

Marc Scanio

KEY TERMS

10-deacetyl baccatin III

—A naturally occurring compound that can be converted to paclitaxel and docetaxel.

Hypersensitivity

—An abnormally sensitive reaction to a stimulus. Similar to an allergic reaction.

Microtubles

—A tubular structure located in cells that help them to replicate.

Taxoid

—A complex molecule that is chemically similar to paclitaxel.

Therapeutic index

—A ratio of the maximum tolerated dose of a drug divided by the dose used in treatment.