ORLANDO – The addition of docetaxel to androgen deprivation therapy significantly reduces PSA progression, but is coupled with significant toxicity in hormone-naive metastatic prostate cancer, according to results of a phase III multicenter trial from France and Belgium.
Prostate-specific antigen (PSA) progression, defined as at least a 25% increase from baseline, was observed in 8% of the androgen suppression arm (ADT) vs. 3% of the ADT plus docetaxel (Taxotere) arm at 3 months (P value = .08) and in 10% vs. 1%, respectively, at 6 months (P = .002), Dr. Gwenaelle Gravis reported at the Genitourinary Cancers Symposium.
The addition of docetaxel also significantly increased the likelihood of a PSA response, defined as a decrease of at least 50% from baseline. A PSA response was achieved in 91% of the ADT plus docetaxel arm vs. 80% of the ADT arm at 3 months (P = .008) and in 95% vs. 86% when assessed at 6 months (P = .01), said Dr. Gravis of Institut Paoli-Calmettes, Marseille, France.
Data on the study’s primary end point of overall survival are not yet available, but the current findings are noteworthy in light of recent work by the Southwest Oncology Group demonstrating that PSA progression at 7 months is a strong predictor of death in metastatic hormone-sensitive and castration-resistant prostate cancer (J. Clin. Oncol. 2009;27:2450-6).
The French researchers randomized 192 patients to ADT plus docetaxel 75 mg/m2 every 3 weeks for up to nine cycles and prednisone; and 193 to ADT alone, which could include use of luteinizing hormone–releasing hormone agonists or maximum androgen blockage or orchidectomy. Patients were stratified according to prior systemic treatment and Glass risk group.
After accrual of 215 patients, 3 toxic deaths occurred – 2 due to neutropenic fever and 1 to general impairment. This prompted the internal monitoring committee to recommend use of granulocyte-colony stimulating factor from day 5 to day 10 after each docetaxel administration, with no subsequent deaths occurring, Dr. Gravis said.
Grades 3/4 hematologic toxicity in 188 evaluable ADT plus docetaxel patients include anemia (2%), neutropenia (32%), febrile neutropenia (7%) and septic death (1%), while only 1% anemia was reported in 185 evaluable ADT-only patients. Other notable grade 3/4 toxicities in the ADT plus docetaxel vs. ADT alone arms include fatigue (7% vs. 1%), erectile dysfunction (9% vs. 8%), decreased libido (6% vs. 5%), and hot flushes (4% vs. 2%).
"Docetaxel was associated with a significant increased, but manageable toxicity," Dr. Gravis said at the symposium, cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.
Global quality of life scores were equivalent in both arms at 12 months in the GETUG-AFU 15/0403 study, sponsored by the National Federation of Comprehensive Cancer Centers with the collaboration of the French Association of Urology (AFU).
At baseline, the patients had a median age of 63 years and roughly half had a good performance status. The median PSA was 27 ng/mL, median Karnofsky score was 100 and 58% had a Gleason score of 8 or more.
Less than 30% received radical prostatectomy or radiotherapy and less than 10% received systemic treatment with chemotherapy or hormonal therapy. Most patients had up-front metastatic disease, with bone metastases present in 81% and nodes metastases in 55%, Dr. Gravis said.
The trial was supported by grants from the French Health Ministry, Sanofi-Aventis, AstraZeneca and Amgen. Dr. Gravis and her co-authors disclosed no conflicts.