CHICAGO–The addition of docetaxel to hormonal therapy at an early stage in nonmetastatic high-risk prostate cancer patients reduces risk of prostate-specific antigen (PSA) relapse by 9–26%, reported Stephane Oudard, MD, of the George Pompidou European Hospital, Paris, and colleagues at the American Society of Clinical Oncology’s 2011 Annual Meeting.

The primary endpoint in this multicenter, randomized Phase 3 study was PSA progression-free survival (PFS). Secondary endpoints were PSA response, duration of PSA response, time to clinical progression, overall survival, tolerability, and quality of life. Progression definition: not-responding patients, 25% PSA increase above baseline; responding patients, PSA increase >25% above nadir (3 values) above 0.1ng/mL with absolute increase (AI); no definition of AI is available for PSA progression in this setting, therefore AI was incremented from 0.2 to 2ng/mL by 0.1 step.

Patients were randomized to receive either A (n=125): hormonal therapy + docetaxel (70mg/m2 every 3 weeks for 6 cycles) or B (n=126): hormonal therapy (triptorelin, every 3 months for 1 year in patients with nonmetastatic prostate cancer at high-risk of recurrence after radical prostatectomy (RP) and/or radiotherapy (RT). Stratification factors: RP vs. RT and PSA doubling time (PSA-DT) less than or greater than 6m. Inclusion criteria were at least 1 of: Gleason >8, PSA-DT <6m, positive surgical margins, PSA velocity >0.75ng/mL per year, pathological pelvic lymph nodes, time from RP/RT to inclusion <12m. Within 90 days before inclusion, at least three consecutive progressive PSA >0.2ng/mL (RP) or >1ng/mL (RT). Of the 251 intent-to-treat patients, 125 were in Arm A and 126 were in Arm B.

The median age of the two groups (Arm A vs. Arm B, respectively) was 64 years vs. 66 years; time from initial diagnosis to inclusion 35 months vs. 34 months; ECOG=0, 97%  vs. 95%, Gleason score >8, 32% vs. 27%; RP, 69.6%  vs. 71.4%; RT, 37.6% vs. 38.1%; and PSA-DT <6m, 53.6% vs. 53.2%.

PSA response (% patients) in Arm A vs. Arm B was: complete response, 73 vs. 64; partial response, 21 vs. 33; PSA increase ≥25% above baseline value, 6 vs. 2. Upon variation of AI, hazard ratio A vs. B spread between 0.74 and 0.91 (P<0.05 for AI=0.8–0.9ng/mL), favoring the combination of docetaxel + hormonal therapy. A risk reduction was observed in Arm A vs. Arm B regardless of  AI. Results were identical at 25% or 50% increase above nadir.

“Given that the lowest hazard ratio was obtained for about 1.0ng/mL of PSA, we suggest a new definition of PSA relapse in the rising PSA population: biological progression is defined by a PSA increase of 25% above nadir.

Among patients in Arm A, the primary Grade 3 and 4 hematological toxicity was neutropenia (48%, 15% received growth factors), followed by febrile neutropenia (8%, one life-threatening), thrombocytopenia (3%, one received platelet transfusion), and anemia (0.8%, one patient received red blood cell transfusion). Nonhematological toxicities in Arm A included Grade 3 and 4 alopecia, asthenia, nausea, vomiting, and nail changes. The most common Grade 1 and 2 toxicity in Arm A was asthenia, occurring in 73.6% of patients. Toxicities for both arms were reported at ASCO 2010 (Abstract 4685).

Dr. Oudard et al concluded that the addition of docetaxel to hormonal therapy at an early stage in nonmetastatic high-risk prostate cancer patients is safe and efficacious. Clinical PFS monitoring is ongoing.