Background
SWOG 99-16. Phase III RCT; 674 men with progressive metastatic androgen-independent (castration-resistant) prostate cancer. Progression defined by enlarging bidimensional lesion, new bone-scan disease, or two PSA rises ≥7 days apart.
Interventions and follow up
Arm A: Estramustine 280mg TID (days 1–5) + docetaxel 60mg/m2 (day 2, escalated to 70mg/m2 if no grade 3–4 toxicity) + dexamethasone premedication, q21d.
Arm B: Mitoxantrone 12mg/m2 (day 1, escalated to 14mg/m2 if tolerated) + prednisone 5mg BID, q21d.
Primary endpoint: Overall survival.
mFollow up: 32mo.
Arm B: Mitoxantrone 12mg/m2 (day 1, escalated to 14mg/m2 if tolerated) + prednisone 5mg BID, q21d.
Primary endpoint: Overall survival.
mFollow up: 32mo.
Results
mOS: 17.5mo vs 15.6mo, arm A vs B; HR 0.80, 95%CI 0.67–0.97; P=.02.
mPFS: 6.3mo vs 3.2mo, arm A vs B; P<.001.
PSA decline ≥50%: 50% vs 27%, arm A vs B; P<.001.
mPFS: 6.3mo vs 3.2mo, arm A vs B; P<.001.
PSA decline ≥50%: 50% vs 27%, arm A vs B; P<.001.
Adverse events
Grade ≥3 (arm A vs B): Cardiovascular 14.5% vs 6.7%; nausea/vomiting 20% vs 5.2%; pain 10.6% vs 5.2%.
Infectious/hematologic: Infection 13.6% vs 6.7%; hematologic toxicity 19.7% vs 15.5%.
Infectious/hematologic: Infection 13.6% vs 6.7%; hematologic toxicity 19.7% vs 15.5%.
Conclusions
Docetaxel + estramustine modestly improved overall survival versus mitoxantrone + prednisone in metastatic castration-resistant prostate cancer, at the cost of greater toxicity.
Key Limitations
Estramustine adds thromboembolic and GI toxicity and is no longer used; the contemporaneous TAX 327 trial established single-agent docetaxel + prednisone (every-3-week schedule) as the preferred, better-tolerated standard.
Clinical Context
With TAX 327, SWOG 99-16 established docetaxel-based chemotherapy as the first regimen to improve survival in mCRPC, supporting the docetaxel + prednisone backbone in ASCO/ESMO guidelines; estramustine is not part of current practice.