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Prostate cancer drug seen as possible breakthrough

The survival rate more than doubled among most men in the study. Abiraterone works by 'starving' tumors.

July 23, 2008|Thomas H. Maugh II | Times Staff Writer

An experimental cancer drug shrank prostate tumors dramatically and more than doubled survival in 70% to 80% of patients with aggressive cancers, British researchers reported Tuesday.

Although the study published in the Journal of Clinical Oncology covered only 21 patients, the drug is now being tested in more than 250 men with what appears to be similar results, experts said.

"There is a general sense in the prostate cancer community that this agent is extremely promising and is very likely to have an important role in the management of prostate cancer patients," said Dr. Howard M. Sandler, a radiation oncologist at the University of Michigan who is a spokesman for the American Society of Clinical Oncology.

"It's pretty safe to say that we are going to have a lot more to offer patients when this drug gets approved," added Dr. Robert Reiter, a urologist at UCLA's Jonsson Comprehensive Cancer Center who was not involved in the research.

Experts expect the new drug, called abiraterone, to be widely available by 2011. It could find use among most of the 28,000 U.S. men diagnosed each year with the most aggressive and almost-always fatal type of prostate cancer.

The trial was sponsored by Cougar Biotechnology Inc. of Los Angeles, which holds the patent rights to abiraterone.

The drug is also being tested for breast cancer, but no results have been released yet.

Key to the excitement is the drug's unusual way of working.

Prostate cancer is fueled by the male hormone testosterone. One method of treatment is known as hormonal deprivation or "chemical castration," in which drugs block production of the hormone by the testes and the adrenal gland.

Yet many tumors continue to grow. Recent research has shown that tumor cells themselves produce testosterone.

Researchers at the Institute of Cancer Research in London developed abiraterone to block an enzyme called cytochrome P17, which is crucial in converting cholesterol to testosterone. The point, Sandler said, is that the drug blocks testosterone production everywhere in the body, including inside the tumor cells.

"This agent can eliminate virtually all testosterone from the bloodstream . . . which seems to be important for patients because cancer may be sensitized to the presence of minute levels of testosterone," he said.

The drug also blocks the production of estrogen, which is why researchers hope it will prove useful in breast cancer.

In the new study, Dr. Johann S. de Bono of the institute and his colleagues studied 21 men whose tumors were resistant to chemical castration. The men were given once-daily oral doses of abiraterone.

"The drug is spectacularly effective," De Bono said. "The tumors shrink, the pain goes away. Some patients . . . have been on it for up to two years and eight months and are still doing well."

Reiter noted that "these guys were at the end stage of disease, the worst stage of cancer, and 70% responded in a clinically meaningful way. That's pretty dramatic . . . and is likely to lead to a major change in therapy."

Historically, he added, most such patients die within six months.

Side effects were minimal.

Simon Bush, a 50-year-old retired banker in London, was one of the patients in the trial. First diagnosed with prostate cancer three years ago, he tried all other forms of therapy without success.

"Last year, I was in severe pain because of my prostate cancer, which had worsened and spread to my bones," he said.

He began taking abiraterone in May 2007, and the improvement began within a week. Within two months, he said, his PSA level -- a marker of tumor growth -- had dropped by 95%.

Within three months, he had stopped taking painkillers entirely and was able to resume a normal life.

"The changes in my life have been dramatic, from managing thousands of people in a major bank to facing a very uncertain future, then to renewed hope, thanks to this drug trial," Bush said.

Dr. Glen Justice, director of Orange Coast Memorial Medical Center's Cancer Center in Fountain Valley, noted: "What is exciting about this drug is that it had activity in both earlier and later stages of disease. . . . The question is: Can we take people that have a very aggressive disease that was caught early and increase the cure rate by using it upfront?"

--

thomas.maugh@latimes.com

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