Bicalutamide and Flutamide, Each in Combination with Luteinizing Hormone‐Releasing Hormone Analogs, in Advanced Prostate Cancer: Exploratory Analysis of Impact of Extent of Disease by Bone Scan on Outcome

Abstract

Objectives: We performed an exploratory analysis to determine whether there was a difference between two antiandrogen‐plus‐luteinizing hormone‐releasing hormone analogs (LHRHas) combinations in patients with minimal or extensive disease. Materials and Methods: Data from a prospective, randomized, double‐blind study with a median follow‐up of 160 weeks were used to perform an exploratory analysis of outcome with 2 combined androgen blockade regimens in 813 advanced prostate cancer patients based on disease status at entry (minimal or extensive disease). A total of 404 patients received bicalutamide plus LHRHa, and 409 patients received flutamide plus LHRHa. Patients were grouped prospectively by “extent of disease” as determined by bone scan: minimal disease was defined as zero to five lesions, while extensive disease was defined as greater than or equal to six lesions. Patients with no lesions on bone scan (0 lesions) had to have at least one measurable nonskeletal metastasis. Results: Patients with minimal disease receiving bicalutamide plus LHRHa demonstrated a trend to longer survival as reflected by a hazard ratio (HR) of 0.79 (95% confidence interval 0.59–1.07), but this was not statistically significant. In the extensive disease group, the effects of bicalutamide plus LHRHa and flutamide plus LHRHa on disease progression and survival were similar (HR 0.96 and 0.90, respectively). Conclusions: Our results are consistent with previously published data demonstrating that patients with stage D2 prostate cancer and minimal disease have a better outcome than patients with extensive disease. In the patients with minimal disease per bone scan, there was a trend toward a benefit for bicalutamide plus LHRHa compared with flutamide plus LHRHa in terms of survival, but not in terms of disease progression.

Treatment of PSA only Recurrence of Prostate Cancer After Prior Local Therapy

“…There was a trend for improved survival (8 months) and reduced risk of disease progression in bicalutamide-treated patients. Further exploratory analysis revealed that patients with minimal metastatic disease treated by either treatment regimen had a better outcome in terms of survival than did patients with more extensive disease [120]. There was a significantly (26% vs 12%, P < 0.001) higher incidence of diarrhea and more withdrawals due to diarrhea (25 vs. 2 patients) in the flutamide plus LHRH agonist therapy group compared with the bicalutamide plus LHRH agonist group.…”

“…Results have ranged from a 2-3% improvement in survival benefit in the Prostate Cancer Trialists' Collaborative Group study [116], to a 22% benefit found by Caubet and colleagues [114] for MAB with non-steroidal antiandrogens compared with standard hormonal monotherapy (orchiectomy or LHRH agonist therapy), which translated into a 7-month survival benefit. Some studies [117,119,120], but not all [112], have found that patients with minimal metastatic disease have a more pronounced survival benefit with MAB. It is possible (but not yet proven) that PSA-only recurrence patients could represent a similar subgroup that would have better survival with MAB.…”

The Prostate Cancer Continuum: The Role of Bicalutamide (Casodex®)

“…An exploratory analysis by extent of disease indicated that, as expected, survival was better for patients with minimal disease (i.e., five or fewer bone metastases). For these patients, a trend toward survival benefit for bicalutamide was observed (65).…”

Hormonal therapy options for prostate‐specific antigen‐only recurrence of prostate cancer after previous local therapy

“…Several studies have investigated the extent of disease as a prognostic factor for overall survival with MAB, and some [15,16], although not all [17], reported better survival benefits in patients with minimal metastatic disease. For example, a trial conducted by the US National Cancer Institute (NCI) in 603 patients with metastatic prostate cancer showed a significant overall survival benefit for MAB with flutamide plus leuprolide vs placebo plus leuprolide, and analysis of data by extent of disease showed that the treatment difference was particularly evident in the subset of patients with minimal metastatic disease and normal performance status [15].…”