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Taxol (Paclitaxel)

Taxol is a brand name chemotherapy drug that has been in use with U.S. Food and Drug Administration (FDA) approval since 1992. The history of this drug dates back decades earlier. It is a natural compound derived from the Pacific yew, a type of tree. The first samples of the bark removed and tested for medicinal properties were harvested in 1962, but it took nearly 30 years to result in an approved anti-cancer drug.

With the generic name paclitaxel, this drug is now made and sold by a number of pharmaceutical companies and has been approved for use in the treatment of several types of cancer. Researchers are hopeful that this drug can prove useful in treating mesothelioma as part of a multimodal approach, but initial studies have had limited and mixed results.

What is Taxol?

Taxol is a brand name drug used to treat several types of cancer. Other names for this drug include the generic name, paclitaxel, as well as Praxel, Bristaxol, Onxol, Abraxane, and Asotax. It was first approved by the FDA in 1992 and is currently approved to treat breast cancer, ovarian cancer, lung cancer, and AIDS-related Kaposi’s sarcoma. Common unapproved uses include the treatment of esophageal, head and neck, endometrial, bladder, and cervical cancers. Taxol is not commonly used to treat mesothelioma, but researchers continue to test this drug in combination with other drugs and other types of therapy for mesothelioma patients.

The History of Taxol

Today, Taxol is a very important drug, particularly for treating advanced ovarian cancer in patients who have not responded to other treatments. The discovery of this natural compound came as a result of National Cancer Institute (NCI)-funded research. It began in the 1950s when the NCI began a research project to screen synthetic and already known compounds for chemotherapeutic properties.

In the 1960s the NCI partnered with the U.S. Department of Agriculture to begin screening natural compounds from plants. Over a couple of decades, more than 30,000 compounds were screened, and the compound that would become Taxol was discovered. Paclitaxel was isolated from the bark of the Pacific yew tree, and was studied for decades. Finally in 1977 it was proven to be effective at stopping tumor growth in mice and was then used in clinical trials and eventually approved by the FDA in 1992. The ultimate test was a study that showed 30 percent of women with advanced ovarian cancer responded to the drug. Taxol is now the best-selling cancer drug of all time and research into how it can help patients continues.

How it Works

Paclitaxel is a type of drug called an antimicrotubule agent. Like other chemotherapy drugs it targets cells in the body that grow and divide rapidly and slow or stop their growth. The way antimicrotubules do this is by interfering with microtubules and how they arrange during cell division. These proteins have to line up in a certain way inside a cell for that cell to divide and reproduce. Paclitaxel interferes with this process.

Side Effects

As with any type of chemotherapy, there are likely side effects when using Taxol. It is a cytotoxic drug and harms healthy cells along with cancer cells. The most common side effects seen with paclitaxel include pain and swelling at the injection site, nausea, vomiting, diarrhea, muscle and joint pain, weakness, stomach pains, mouth sores, and hair loss. These are largely not serious, but they can be very uncomfortable and sometime painful. The nausea and mouth sores can both make eating more challenging, so patients may also experience weight loss on this drug.

Black Box Warnings

In addition to the less serious and more common side effects that most patients experience with Taxol, there is a potential for more severe adverse events. The FDA has labeled Taxol with a black box, which it reserves for the most serious and potentially life-threatening side effects of drugs. One of these is the risk that Taxol will significantly reduce white blood cell count, which makes a patient susceptible to dangerous infections. Patients with already compromised immune systems are cautioned not to use this drug or to be carefully monitored while on it.

Another risk is related to the fact that there are two different forms of paclitaxel, each one manufactured with a different supplemental ingredient to help the drug get to the tumor. These are used for specific types of cancer and will be less effective if not used correctly. One of the additives is polyoxyethylated castor oil and some people may have a life-threatening allergic reaction to it.

Treating Mesothelioma

Because Taxol proved to be so successful in advanced ovarian cancer, in patients who had little hope of any treatment working, researchers have been eager to find out what else this drug can do. Unfortunately results in trials with mesothelioma patients have not produced results as successful as those seen in ovarian cancer. Early trials with Taxol and mesothelioma patients used it as a single agent drug, and patients saw little to no improvement. Survival times in these studies were only five to nine months, not a great improvement over other treatments.

More recently researchers have combined paclitaxel with other treatments in mesothelioma patients and are hoping for better results. A published case study of a woman with peritoneal mesothelioma showed there should be hope for this drug. She was given intraperitoneal carboplatin with paclitaxel and achieved complete remission after six cycles. The doctors treating her concluded that combinations with paclitaxel, given aggressively, could help other patients with mesothelioma. There have also been some promising animal studies, including using nanoparticles in mice to deliver paclitaxel, that may ultimately end up in human trials. The mice benefitted from the use of Taxol after cytoreductive surgery, a possible treatment plan for human patients in the future.

While early studies of Taxol in mesothelioma patients were disappointing, more recent studies, combining this drug with other drugs and as part of a multimodal treatment approach, are showing great promise. Taxol may be a drug used more commonly in the future for treating patients with all types of mesothelioma. The risks of the drug may be very serious, but are no worse than those seen with other chemotherapy drugs.

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