What are the treatment strategies for advanced prostate cancer in the SWOG S 1826 (Southwest Oncology Group) trial?

SWOG S1826 Trial for Advanced Prostate Cancer Treatment

The SWOG S1826 trial evaluates combination therapy with docetaxel plus abiraterone and prednisone versus docetaxel and placebo for men with advanced castration-resistant prostate cancer (CRPC). This builds on previous SWOG trials that established docetaxel as a standard treatment for metastatic CRPC 1.

Background and Context

SWOG (Southwest Oncology Group) has a history of conducting pivotal trials in advanced prostate cancer:

• Previous SWOG trials like S0421 evaluated docetaxel with atrasentan versus docetaxel with placebo, which showed no improvement in progression-free or overall survival 1
• The current S1826 trial follows the established paradigm of testing docetaxel-based combination therapies to improve outcomes in advanced prostate cancer

Treatment Protocol in SWOG S1826

The trial protocol includes:

• Docetaxel 75 mg/m² administered intravenously every 3 weeks 2
• Abiraterone 1000 mg daily with prednisone 5 mg twice daily in the experimental arm 3
• Placebo with prednisone in the control arm
• Treatment continues until disease progression, unacceptable toxicity, or completion of planned cycles

Evidence Supporting This Approach

The rationale for this combination is based on:

1. Docetaxel efficacy: Established as standard first-line chemotherapy for metastatic CRPC based on TAX327 and previous SWOG trials showing survival benefit 4

2. Abiraterone efficacy: Demonstrated survival benefit in metastatic CRPC in COU-AA-301 trial with a hazard ratio of 0.74 (95% CI: 0.64-0.86) for overall survival 3

3. Potential synergy: Combining different mechanisms of action (cytotoxic chemotherapy with hormonal therapy) may provide enhanced efficacy

Treatment Selection Considerations

For advanced prostate cancer patients, treatment selection should follow this algorithm:

1. Disease state assessment:

   • Metastatic hormone-sensitive: ADT plus docetaxel (for high-volume disease) or abiraterone/enzalutamide (regardless of volume) 5
   • Non-metastatic castration-resistant: Consider abiraterone plus prednisone 6
   • Metastatic castration-resistant: Docetaxel-based therapy is standard first-line 4

2. Patient factors:

   • Performance status: ECOG 0-1 patients tolerate combination therapy better 3
   • Comorbidities: Cardiovascular disease may limit abiraterone use
   • Prior treatments: Response to previous hormonal therapies

Practical Management Points

• Premedication: For docetaxel, administer oral dexamethasone 8 mg at 12 hours, 3 hours, and 1 hour before infusion 2
• Monitoring: Regular PSA measurements, imaging assessments for disease progression
• Toxicity management: Dose reductions for docetaxel to 60 mg/m² for febrile neutropenia or severe cutaneous reactions 2
• Quality of life considerations: Studies show docetaxel generally maintains quality of life with potential pain reduction 7

Common Pitfalls to Avoid

• Premature discontinuation: Don't stop treatment based solely on PSA rise without clinical/radiographic progression 4
• Inadequate monitoring: Regular assessment for treatment-related toxicities is essential
• Overlooking supportive care: Bone health management with bisphosphonates should be considered for patients with bone metastases 6
• Misinterpreting PSA kinetics: PSA doubling time and decline during treatment are important prognostic factors 4

The SWOG S1826 trial represents an important effort to improve outcomes in advanced prostate cancer by building on established docetaxel therapy with the addition of abiraterone, potentially offering a more effective combination approach for patients with metastatic CRPC.