Biclutamide ("Casodex") 150 mg as Adjuvant to Radiotherapy in Localized or Locally Advanced Prostate Cancer

Ryan Smith, MD
University of Pennsylvania Cancer Center
Last Modified: November 4, 2001

Presenter: C. Tyrrell
Affiliation: Plymouth Oncology Centre, Plymouth, United Kingdom

Background
Biclutamide (Casodex) is often used as adjuvant therapy in patients who have biochemical failure after definitve therapy. This is a study to evaluate the use of biclutamide as an immediate therapy or as adjuvant to therapy of curative intent in non-metastatic prostate cancer.

Materials and Methods

Prospective double blind trial of 8113 patients

Patients were randomized to biclutamide 150 mg/day vs placebo in addition to standard care (Radical Prostatectomy (RP)=55%, XRT=17%, watchful waiting=28%) for localized or locally advanced prostate cancer.

Approximately 67% were T1/T2, 30% were T3, and 2% were T4

2% had positive lymph nodes

33% had Gleason Score (GS) 7-10, 45% GS 5-6, 22% GS 2-4

17% underwent XRT, 55% had RP, 28% underwent watchful waiting

Primary endpoints were objective disease progression and overall survival

Secondary endpoints were PSA progression, treatment failure, and tolerability

Evaluated as intent to treat with a median follow-up of 3 years

Results

Risk of objective disease progression for all patients was reduced by 42% with the addition of biclutamide compared to standard therapy alone, regardless of underlying therapy.

Largest risk reduction was seen in those patients with T3-T4 disease (Hazard ratio of .40)

Bone metastases were reduced by 33%

PSA progression was reduced by 59%

For entire population, event free survival was approximately 80%

Overall survival for entire group was 94% with follow up of 3 years

85% had either gynecomastia, breast pain, or both

9% reported impotence, 9% hot flashes

25% of patients in the biclutamide group withdrew

Author's Conclusions

Biclutamide reduces the risk of progression of prostate cancer

Many had side effects, though >90% were mild or moderate. These side effects dissipated when hormones were removed

Clinical/Scientific Implications
Biclutamide was used as an immediate adjuvant therapy in this study. Although there was a significant risk reduction with biclutamide, it was employed in a patient population that has a low risk of disease progression. With a control group freedom from progression of 80%, this translates into a number of patients treated who probably did not need the hormonal therapy. There was no data on disease control and control of symptoms when patients failed and other forms of adjuvant therapy was used (i.e.-LHRH agonists). In this group of patients, overall survival was 94% at 3 years, while historically, OS is often 96-98% at ten years. Therefore, these may be more advanced or aggressive than indicated. The side effect profile is concerning with 85% complaining of gynecomastia/breast pain, though the severity was not presented. The 9% impotence rate is very low, when even with primary therapy alone (XRT or RP), impotence is often in the range of 40%. Therefore, this is likely grossly underestimated. Multivariate analysis was not done, so it is not known if "traditional" indicators of disease aggressiveness (PSA, Gleason Score, T stage) would explain the disrepencies between the two groups. Follow-up of 3 years is very short for a study of prostate cancer and longer follow-up is needed.