From "The Oregonian" - May 16, 2005

OHSU drug 'step forward' against cancer

In a study of late-stage prostate cancer that the university worked on, a
vitamin D formula, DN-101, adds at least seven months to men's lives.

by ANDY DWORKIN

A highly potent form of vitamin D, developed at Oregon Health & Science
University, might markedly extend the lives of men dying from prostate
cancer, a new study shows.

Men in the study had advanced tumors growing despite surgery or radiation
and subsequent treatment with drugs that block male hormones. Doctors now
give such patients the chemotherapy docetaxel, which lets them live for
about 16 months, on average. Adding the experimental vitamin pill DN-101 to
that chemotherapy increased the average expectancy to roughly two years.

A two-year survival "is the highest ever seen in a randomized study," said
Dr. Bruce Montgomery, a Seattle Cancer Care Alliance prostate cancer expert
who was not involved in the research. "It clearly is a big step forward."
Although researchers know DN-101 added at least seven months to the average
survival, they can't yet calculate the new median life expectancy. That's
because more than half the men who took DN-101 in the study are still alive,
said Dr. Tomasz Beer, the OHSU Cancer Institute scientist who helped develop
the drug.

The treatment "has a lot of guys I see every day getting a meaningful chunk
of extra time, without any extra side effect," said Beer, who unveiled the
study results Sunday at a cancer conference in Orlando, Fla.

" 'I'm . . . excited' would be an understatement," he said.

Such late-stage cancers kill more than 30,000 U.S. men every year, according
to the American Cancer Society.

The study reported Sunday followed 250 men, randomly assigned to receive
either docetaxel alone or with DN-101. Among the 125 men who used the chemo
drug alone, the median survival was 16.4 months. The median survival among
men who also took DN-101 is an additional 7.1 months, and counting.

Most prostate cancer patients will have to wait for that benefit. The
250-patient study was of a middling size: big enough to indicate the pills
extend life, but not big enough to prove DN-101 is ready for market. That
will take a study with about 600 men, Beer said.

When a larger study might start is unclear. Officials with DN-101's
manufacturer, South San Francisco-based Novacea Inc., want to meet with the
Food and Drug Administration before deciding how to proceed, Chief Executive
Officer Brad Goodwin said. He would not estimate when the drug might be
ready for sale.

In the meantime, the study should not drive men with cancer to buy huge
bottles of vitamin D pills. The vitamin in DN-101, calcitriol, is a special
form of vitamin D that can safely deliver large doses. Standard vitamin D
pills could cause dangerous overdoses in large quantities.

Until recently, men with late-stage prostate cancer got chemotherapy that
eased their pain but did not extend their lives. Then last year, two studies
showed that docetaxel not only eased pain but also added about three months
to those patients' lives, pushing average survival to more than 16 months.
Docetaxel became the new standard, on which doctors are trying to improve.

Montgomery said the DN-101 study is part of a push to find safe medicines
that make cancers more susceptible to the toxins in chemotherapy drugs. Some
of those compounds are in use, such as Herceptin, an antibody that can team
up with chemo to more aggressively fight some breast cancers. Scientists
including Montgomery are searching for similar compounds that can help
battle prostate cancer. The DN-101 research "is the first study that shows
this class of agents" can be a big help, he said.

How DN-101 helps fight cancer isn't clear, Beer said. Prostate tumors have
receptors for vitamin D, biological docking stations that let the vitamin
affect cancer cells. Calcitriol seems to interfere with those cells' growth,
Beer said. It also seems to aid a biological process akin to cellular
suicide called apoptosis, which destroys some useless cells.

Certain other cancers -- including some breast, pancreas and ovarian
tumors -- also have vitamin D receptors, Beer said. In theory, DN-101 might
help fight those tumors. So far, no experiments have shown whether
calcitriol helps people with nonprostate tumors.

If DN-101 makes it to market, OHSU stands to profit. The university licensed
the drug to Novacea in 2002, getting payments including stock in the
privately held company and royalties on any sales of the drug.

Beer, who has been working on calcitriol for eight years, is listed on the
license but said he has no other financial ties to Novacea. Because of the
licensing agreement, OHSU's Conflict of Interest in Research Committee put
certain restrictions on his participation in the just-finished trial. Beer
planned the study and reported the results, but he did not care for any of
the men in the study.