Taxotere, a semisynthetic compound structurally related tothe cancer treatment taxol, has been isolated from arenewable source, needles from the Pacific yew tree.

Taxol has been hailed by some as the most important newcancer drug in 15 years, but the only natural source of taxol isthe bark of the yew tree.

Taxotere, on the other hand, is the product of a processdeveloped by Rhone-Poulenc for the partial synthesis of taxolmolecules, according to Martin Raber of the University of TexasM.D. Anderson Cancer Center. He is co-author of a report in theDec. 2 issue of the Journal of the National Cancer Institute (NCI)that reported results from Phase I safety studies.

Raber said Rhone-Poulenc found that taxotere was the mostactive molecule in vitro of all the molecules it studied.

According to the NCI report, the taxotere study involved 39cancer patients, and anti-tumor activity was observed in six of10 patients with ovarian cancer, including one who had fullregression of the disease. One of three breast cancer patientstreated with the compound showed improvement.

Reports of side effects such as mouth sores and fever, andinfection caused by a plunge in white blood cells with taxotere,and nerve damage, muscle pain, and disturbances in heartrhythm with taxol were discounted by medical experts.

"There really isn't much difference in the two drugs that Iknow of," said Bruce Chabner of the NCI in Bethesda, Md. "Theside effects of taxol in our studies have been minimal."

Chabner said the only side effect noted when using the doserecommended by the Oncologic Drug Advisory Committee(ODAC) in both drugs appeared to be granulocyte suppressionin bone marrow, and at higher doses neurotoxicity andmucositis.

According to Rabner, taxotere, like taxol, is an extremely activechemotherapeutic with a lot of promise.

"The tumor types that one sees responses in with taxotere aresimilar to those in taxol," he said.

Raber added that although the drugs are administered atdifferent doses, they show a similar toxicity profile.

"The drugs are being used in the same way, so it's not clear tome that they have superimposable profiles," Raber said. "Thetoxicity of myelosuppression and the toxicity ofhypersensitivity is common to both drugs. With regard toneurotoxicity and cardiac toxicity, we don't have enoughexperience to comment, and so it's too early to say that onecompound is more or less toxic than the other."

A method to synthetically produce taxol will probably solvesupply problems that have limited its availability. It takes thebark from about three adult Pacific yew trees to produceenough taxol to treat one patient. The compound used toproduce taxotere comes from a renewable source, yew needles.

However, Patricia Padgett Lea, an analyst with VectorSecurities International in Deerfield, Ill., doesn't thinkproduction of taxol or taxotere is the key issue. Lea saidBristol-Myers Squibb Co. (BMS) is also employing asemisynthetic process that uses yew needles to providefeedstock for taxol.

"They're (BMS) scaling up this process and hope to produce 230kg. by the end of 1993, so they're not that far away from beinga non-environmental threat. They may not need yew bark atall by then."

Lea said taxotere may ultimately prove easier to use. "It's amore soluble drug and easier to administer."

But Raymond Moshy, president and chief executive officer ofEscagenetics Corp. of San Carlos, Calif., said: "Our view is thattaxol will be the significant compound, so we're scaling up ourtaxol production. We think the plant cell tissue culture processwill be more direct and economical."

However, Moshy is hedging his bets in the case taxoterebecomes a contender or the semisynthetic production of taxolreplaces Escagenetics' method. The company is also developing10-Deacetyl baccattin III, the compound used as anintermediary for the semisynthesis of taxotere, Moshy toldBioWorld.

"Possibly we need to be prepared to offer either one or both,"he said. "But taxotere is somewhat behind taxol in clinicaldevelopment; it still has a long clinical period to go through."

-- Michelle Slade Associate Editor

(c) 1997 American Health Consultants. All rights reserved.

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