Phase II study of neoadjuvant docetaxel and androgen suppression (AS) plus radiation therapy (RT) for high-risk localized prostate cancer (HRLCaP)
Journal Articles
Overview
Research
Identity
Additional Document Info
View All
Overview
abstract
4631 Background: Docetaxel increases survival in hormone-refractory prostate cancer and is active in hormone-sensitive disease. In HRLCaP, improvement upon AS plus RT is required, as many patients eventually develop metastases. This trial’s objective was to assess the tolerability of neoadjuvant docetaxel plus AS and RT in men with HRLCaP. Methods: Fifty-four men with newly diagnosed previously untreated HRLCaP were accrued to a Phase II single-arm, 2-stage, open-label study involving 7 Canadian centres. All were to receive 3 years of AS (LHRH-agonist + antiandrogen for 4 weeks). Chemotherapy started week 5. Twenty-four men received docetaxel 35 mg m2 iv weekly × 6 q8 weeks for 2 cycles, RT starting week 25. After protocol revision, 30 men received docetaxel 75 mg m2 iv q3 weekly for 4 cycles, RT starting week 21. The primary endpoint was unacceptable toxicity (UT), defined as ≥Grade 3 non-hematologic toxicity (except nausea/vomiting, tearing, short-term fatigue, and easily-controlled diarrhea), grade 4 thrombocytopenia, grade 4 neutropenia lasting >7 days, febrile neutropenia, or toxicity-related RT change (delay>2 weeks, >25% dose reduction). Results: Median age was 68 (49–79) years. Median iPSA was 19.15 (2.8–138) μg/L. Gleason Score and T-stage were ≥8 and ≥T3a in 70.4% and 42.6%, respectively. All patients have completed RT. Adverse events were as expected for docetaxel. UT occurred in 8 patients (14.8%), including 5 with qweekly docetaxel (Grade 3 acute RT-related genitourinary toxicity - 3, Grade 3 docetaxel hypersensitivity - 1, Grade 3 fatigue >2 weeks - 1) and 3 with q3 weekly docetaxel (Grade 3 acute RT-related genitourinary toxicity - 1, febrile neutropenia - 1, Grade 4 neutropenia >7 days - 1). The following table summarizes PSA response to neoadjuvant treatment. Conclusions: Neoadjuvant AS and docetaxel plus RT in men with HRLCaP appeared well tolerated. Patients will be followed for other outcomes. This approach will be tested in a phase 3 trial. [Table: see text] No significant financial relationships to disclose.
