Seattle Post-Intelligencer
Copyright 1998
Tuesday, August 11, 1998
News
RESEARCHERS PIN HOPES ON NEW CANCER TREATMENT
CAROL SMITH P-I Reporter
Cancer researcher Dr. Sidney Wallace watched in frustration
and grief as his sister died of breast cancer two years ago. Now,
he hopes a drug he helped develop will spare other patients of a
similar fate.
Wallace was in Seattle recently to meet with Cell
Therapeutics Inc., a Seattle biotech company that has licensed the
rights to a new water-soluble form of paclitaxel, a powerful
anti-cancer drug widely known by the brand name Taxol. Researchers
hope that finding a form of the drug that can dissolve in water
will help patients tolerate higher doses, and make the drug more
effective.
Taxol is derived from the bark of the Pacific yew tree. With
nearly $1 billion a year in sales, it is the biggest cancer drug in
the world. It's also one of the most toxic.
Currently, it is primarily used to treat tumors - especially
breast and ovarian cancers - that haven't responded to other
treatments.
Many companies have been searching for a way to make Taxol
less toxic so that patients could tolerate higher doses to buy them
more time, or perhaps a cure. If the drug were less toxic, it could
also be used sooner in treatment, doctors said.
"Taxol is a very oily drug," said Dr. James Bianco, an
oncologist and chief executive officer of Cell Therapeutics. "It
doesn't dissolve well in water."
Traditionally, doctors have used a combination of alcohol and
castor oil or other solvents to administer the drug intravenously.
But the oil causes some of the toxic side effects of the drug,
limiting how much doctors can use.
"The oil creates hypersensitivity," said Wallace, who
developed the water-soluable drug with his team at the University
of Texas M.D. Anderson Cancer Research Center in Houston. "It
causes chills, fever, nausea, vomiting and low blood pressure."
In high enough doses, it can be life threatening.
"It's pretty noxious," Bianco said.
In current doses, Taxol typically doesn't cure cancer, but
gives the patient more time, Bianco said. If a patient's life
expectancy is less than 4 months, using Taxol could extend it by as
much as a year. But doctors hope they could increase that if
patients could tolerate higher doses of the drug.
There are more than a dozen water-soluble forms of paclitaxel
in development by different companies, including Bristol-Myers
Squibb, the maker of Taxol.
None are on the market yet.
Cell Therapeutics hopes its drug will not only be easier to
deliver, but more effective.
It plans to start early-stage testing in humans soon.
Some of the water-soluble versions that have been tried have
had diminished anti-tumor activity, said Wallace.
"Once they made it more friendly, (the drug) lost some of its
efficacy," Bianco said.
Wallace's compound, however, has shown increased efficacy in
lab animals, according to results published in the journal Cancer
Research.
In mice with ovarian cancer, 25 out of 26 tumors disappeared
completely, he said.
And the drug eliminated all the tumors in mice with breast
cancer.
The drug also appears to be effective in lung tumors in
animals, Wallace said. Studies also show that mice can tolerate
twice as much of the water soluble paclitaxel compared with the
conventional type, Bianco said.
Researchers caution that it is premature to draw conclusions
about how the drug will perform in humans.
If paclitaxel could be made less toxic, however, it could
also extend its usefulness for a variety of other diseases, such as
rheumatoid arthritis or multiple sclerosis, where there is some
evidence that Taxol can be useful.
Wallace got his idea for how to make paclitaxel water-soluble
from a novel source - the oil recovery business.
In 1980, a colleague mentioned an approach for recovering
residual oil from the bottom of a well.
"I thought, 'Hey, I could use that,' " said Wallace.
Eventually, that insight led to Wallace's method, which is to
chemically attach the paclitaxel molecule to a long chain of amino
acids. Amino acids, which are naturally found in the body, are the
building blocks of proteins and are soluble in water.
He only wishes his sister, who had tremendous difficulty
tolerating Taxol, had lived to try the new drug.
"This should afford cancer patients more of a fighting chance
to overcome their illness" Wallace said.
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