What is the standard treatment regimen for prostate cancer using Casodex (bicalutamide)?

Standard Treatment Regimen for Prostate Cancer Using Casodex (Bicalutamide)

Bicalutamide 50 mg once daily in combination with an LHRH analog (such as leuprolide or goserelin) is the FDA-approved standard regimen for Stage D2 metastatic prostate cancer, with treatment initiated simultaneously and continued indefinitely unless disease progression or intolerable toxicity occurs. 1

FDA-Approved Dosing and Administration

• The recommended dose is bicalutamide 50 mg once daily (morning or evening), taken with or without food, at the same time each day 1
• Treatment with bicalutamide must be started at the same time as treatment with an LHRH analog 1
• Bicalutamide 150 mg daily is NOT approved for use alone or with other treatments 1
• If a dose is missed, take the next dose at the scheduled time—do not double the dose 1

Combined Androgen Blockade (CAB) Rationale

• Bicalutamide 50 mg combined with LHRH agonists represents standard maximal androgen blockade therapy for advanced prostate cancer 2
• The 50 mg dose is sufficient when combined with castration therapy because the reduction in testosterone from LHRH analogs decreases competition between bicalutamide and testosterone for androgen receptors 3
• Combined androgen blockade should be considered over castration alone, though increased adverse effects may occur 4

Clinical Efficacy Evidence

• Bicalutamide 50 mg plus LHRH analog demonstrated equivalent efficacy to flutamide 750 mg plus LHRH analog, with a trend toward longer survival and significantly better tolerability 5, 6
• Treatment failure rates were significantly lower at 49 weeks with bicalutamide compared to flutamide, primarily due to lower withdrawal rates from adverse events 7
• The median time to progression and death were longer with bicalutamide than flutamide, though differences were not statistically significant overall 7

Monotherapy Considerations (NOT Standard)

• Bicalutamide 50 mg as monotherapy is less effective than castration and should not be used alone 1, 7
• Bicalutamide 150 mg monotherapy may be discussed as an alternative in non-metastatic disease, but this dose is not FDA-approved and showed inferior outcomes in metastatic disease 4, 5
• The 150 mg dose appeared equivalent to castration only in patients with non-metastatic disease at entry, not in metastatic patients 6, 8

Monitoring Requirements

• Measure serum transaminase levels prior to starting treatment, at regular intervals for the first four months, and periodically thereafter 1
• Hepatotoxicity leading to drug discontinuation occurred in approximately 1% of patients, typically within the first 3-4 months 1
• Continue monitoring PSA levels and disease progression markers throughout treatment 2
• Monitor lipid profiles regularly, particularly in patients on combination therapy with LHRH agonists 2

Important Safety Considerations

• Cases of death or hospitalization due to severe liver injury (hepatic failure) have been reported, generally occurring within the first 3-4 months of treatment 1
• Discontinue bicalutamide immediately if clinical symptoms or signs of liver dysfunction occur 1
• No dosage adjustment is necessary for renal impairment or mild to moderate hepatic impairment 1
• Common adverse effects include breast pain, gynecomastia, and hot flushes, with a lower incidence of diarrhea compared to flutamide 5, 7

Long-Term Management

• Patients on androgen deprivation therapy should be monitored for osteoporosis, fractures, obesity, insulin resistance, lipid alterations, and cardiovascular disease risk 2
• For patients with pre-existing cardiovascular morbidity, bicalutamide 150 mg may be considered as an alternative to long-term LHRH analogs based on cardiovascular risk profiles 2
• Continue LHRH agonist/antagonist therapy throughout treatment duration 9

When to Consider Alternative Agents

• If disease progresses to castration-resistant prostate cancer (CRPC), continue androgen suppression and consider switching to enzalutamide or abiraterone, which demonstrate superior efficacy 4, 9
• Enzalutamide showed significantly better progression-free survival compared to bicalutamide in CRPC (15.7 vs 5.8 months, HR 0.44) 10, 9
• The choice to continue bicalutamide may be based on different side effect profiles and cost considerations despite inferior efficacy 10