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Jury still out on drug treatments for prostate cancer

Reports on the success of treating prostate cancer with drug therapies were varied at the recent American Urological Association conference in Chicago.

"One of the problems in this research is that the gold standard in the industry is the prospective randomized trial," said William Catalona, M.D., professor at Northwestern University. "Americans are not going to allow their treatment for prostate cancer to be determined by the flip of a coin."

Nonetheless, Nelson Stone, M.D., professor of urology and radiation oncology at the Mount Sinai School of Medicine, presented data that found a favorable freedom-from-failure rate of 93% for men with prostate cancer treated with brachytherapy seeds at 160 Gy, and a 95.4% local control rate. Stone studied a cohort of 279 men followed up at 10 years. "In 23% of our cases, we used hormone therapy, which was a combination of luteinizing agents, either leuprolide or Zoladex [goserelin acetate, AstraZeneca], combined with either flutamide or Casodex [bicalutamide, AstraZeneca], two antiandrogens," he said. "Drug [therapy] will kill 80% of the cancer cells," he said. "But it's temporary and it has side effects, such as hot flashes and impotence, which last from three to six months."

Stone found that hormone therapy was beneficial in high-risk patients, and that it did no harm in low-risk patients, meaning that doctors could use the hormone therapies to shrink the prostate, making surgery easier.

Other physicians criticized the data. "A patient might go to see Dr. Stone, and if he doesn't get hormone therapy, it often takes two years for the PSA [prostate specific antigen] to reach its lowest level, meaning that you can't call anyone a failure for at least two years," said Catalona, who found that radical prostatectomy was the most successful treatment in a cohort of more than 35,000 patients. He noted that such definitions could skew the research results.

"Stone's presentation was based on a single-center, noncomparative study, and you can't really make these kinds of statements based on that," said Martin Gleave, M.D., professor of surgery at the University of British Columbia. "After all, we had some data in the mid-'90s from our single institution that showed a benefit for hormone therapy, but those data have not been borne out," he said.

Gleave presented data from a study with a cohort of 549 men with prostate cancer. The study, which started in 1995 and continued through the late '90s, sought to test a hypothesis that treating patients with leuprolide and flutamide for longer periods of time before surgery might improve results. Previous studies had tried hormone therapy for three months and shown no difference, but a hypothesis remained that using the product for eight months instead before surgery might yield better results.

"Previous studies were criticized as underpowered," said Gleave. "Our study showed a reduced recurrence rate from 23% to 12%, but the difference disappeared at six years," he said. Nevertheless, he described the results of his study as "hypothesis-generating" material.

"The centers that enrolled higher numbers of patients had much improved PSA recurrence rates," said Gleave, who speculated that higher-volume centers might have relationships with more skilled surgeons who remove more of the cancer. "And the eight-month group had improved outcomes in intermediate-risk patients at five years," he said.

Gleave speculated that future trials might also look at adjuvant or postsurgery treatment. "You may be able to treat patients for longer—perhaps for as long as two years—and add chemotherapy," he said. But he noted that the results of the study were not good news for proponents of neo-adjuvant hormonal therapy. "It will be difficult to drum up enough interest to do another large neo-adjuvant trial," he said.

Meanwhile, research continues on another proposed pharmaceutical treatment for prostate cancer, atrasentan (ABT-627, Abbott Laboratories), despite setbacks. One phase III trial of the drug continues, while another phase III trial was stopped by an independent data and safety monitoring board in February. "The phase II studies suggested a significant delay in disease progression," said Joel B. Nelson, M.D., professor and chairman of the department of urology at the University of Pittsburgh. A study of 244 patients found that progression was delayed an average of 196 days for patients on atrasentan, compared with 129 days on the placebo.

"Another phase III trial is planned, because the enthusiasm is still quite high," said Nelson, who first became interested in how the drug, the most potent blood vessel constrictor known, might affect changes in bone density caused by prostate cancer.

John Otrompke

 

John Otrompke. Jury still out on drug treatments for prostate cancer. Drug Topics Jun. 16, 2003;147:HSE10.