Adding antiandrogen to castration improves survival

In a poster presentation at the Multidisciplinary Prostate Cancer Symposium, Dr. Klotz pointed out that while there is a convincing rationale to support the combined use of castration and bicalutamide, trials to examine this strategy have not been conducted. However, a look at previously published data may provide evidence of a benefit.

"There are two pieces of data that we have merged in an attempt to derive the best guess of what the benefit is," said Dr. Klotz, professor of surgery at the University of Toronto.

Dr. Klotz noted that when developing new therapies, it is ethical only to conduct studies against the most effective treatment regimen available. However, it is possible to calculate the efficacy of a new therapy agent against placebo, or earlier therapies, by integrating data from different trials that share a common treatment arm.

This methodology also relies on the population of patients in the two trials being similar with respect to important risk factors. The fact that both data sets in this case have a common arm of flutamide plus castration or flutamide plus LHRH analog, and both were carried out in patients with metastatic prostate cancer in the pre-PSA era allowed Dr. Klotz to merge them. This has been done for a number of other drugs where it was no longer possible to compare them with placebo for the disease state for which it is indicated, he said.

Using this methodology, Dr. Klotz found a 98.5% probability that bicalutamide, 50 mg/day, combined with an LHRH analog reduces the risk of death in patients with advanced metastatic prostate cancer compared with castration alone. The survival benefit of 20% compares favorably with that observed in other commonly used cancer therapies.

"To make a long story short," Dr. Klotz told Urology Times, "when we combined the data sets, there was a 13% survival benefit of bicalutamide compared to flutamide in the Schellhammer trial, which looked at 800 patients. There was an 8% survival benefit with flutamide compared to castration. When you combine all that together, you come up with a 20% survival benefit or reduction of mortality with bicalutamide plus LHRH analog compared to LHRH analog alone. It is very clinically significant.

"In metastatic disease, this translates into a 6- to 12-month survival benefit. In addition, the increased side effects of bicalutamide plus castration compared to castration alone are minimal."