Adjuvant Therapy With Casodex Reduces Cancer Progression

SAN FRANCISCO—In men with localized or locally advanced prostate cancer, immediate treatment with the nonsteroidal antiandrogen bicalutamide (Casodex), alone or in addition to standard therapy, significantly reduces disease progression.

The finding comes from an early analysis of data from the largest trial (8,113 patients) of its kind ever carried out, said investigator William A. See, MD, professor and chief of urology, Medical College of Wisconsin, Milwaukee.

The trial was designed to determine whether the benefit of adjuvant hormonal therapy seen in breast cancer with tamoxifen (Nolvadex) can be found in prostate cancer, Dr. See said in an interview after the 37th Annual Meeting of the American Society of Clinical Oncology where he presented the results (ASCO abstracts 705 and 2366).

"The rationale for such a hope," he explained, "lies in the clear similarities between breast and prostate tumors: They both occur in secondary sex organs, are hormonally sensitive, occur late in life, have long lag periods, and are associated with multifocal disease."

The international trial was carried out in three major geographical areas—North America (3,292 patients), Scandinavia (1,218), and Europe, South Africa, Australia, and Mexico (3,603)—and had to take into account cultural differences in prostate cancer treatment patterns. For example, watchful waiting was a frequent treatment modality in Europe and Scandinavia, but was not allowed in North America, Dr. See said.

Patients were randomized to bicalutamide 150 mg/d or placebo, in addition to standard therapy composed of radical prostatectomy, radiotherapy, or watchful waiting. Included patients had prostate cancer with negative bone scans.

At a median follow-up of 3-years, bicalutamide reduced the risk of disease progression by a highly significant 42%, compared with placebo (P < .0001). Of 4,052 patients in the bicalutamide group, 363 progressed, compared with 559 of 4,061 placebo patients.

Exploratory analyses found the disease progression benefit to be independent of both standard treatment modality and extent of disease, Dr. See said.

A 33% reduction in risk of bone metastases for those receiving bicalutamide was also highly significant. Risk of PSA progression, while not a prespecified endpoint, was reduced with bicalutamide by a highly significant 59%, compared with standard care alone.

Overall survival data are immature with 6% overall mortality (more than 2% dying of prostate cancer). "This is analogous to a half-time report. The good news is that we are winning, but there is another half to play, and a lot of things can happen. We will have the survival answer in 2 to 5 years," he said.

Side Effects

As anticipated, the most common side effects with bicalutamide were gynecomastia and breast pain (66% and 73%, respectively). In more than 90% of cases, these effects were mild to moderate, leading to withdrawal in 15.6% of cases. Withdrawals because of gynecomastia and breast pain were 0.6% with standard care alone.

Overall withdrawals were similar between the groups (38.1% for bicalutamide vs 31.8% for standard care alone), but withdrawals due to adverse events were higher with bicalutamide (25.8% vs 8.1%). Withdrawals due to objective progression were lower with bicalutamide (2.6% vs 9.3%).

Dr. See pointed out that the approved bicalutamide dose in the United States is 50 mg/d, and that approval for the 150-mg dose is "being worked on." Importantly, he said, side effects of bicalutamide 150 mg were similar to those reported for 50 mg.

Dr. See concluded: "Immediate treatment with bicalutamide 150 mg, either alone or in addition to standard therapy, in men with localized or locally advanced prostate cancer significantly reduces the risk of disease progression. The risk of gynecomastia and breast pain needs to be balanced against the significant reduction in disease progression."