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PURPOSE: The TAPUR Study is a phase II basket trial that aims to evaluate activity of approved targeted agents in patients with advanced cancers with potentially actionable genomic variants. Data from a cohort of patients with metastatic castrate-resistant prostate cancer (mCRPC) and BRCA1 / 2 mutations treated with olaparib are reported. METHODS: Eligible patients with measurable mCRPC were matched to treatment according to protocol-specified genomic matching rules. Patients had no remaining standard treatment options, Eastern Cooperative Oncology Group performance status 0-2, and adequate organ function. Simon's two-stage design was used with a primary end point of disease control, defined as objective response or stable disease of at least 16-week duration. Secondary end points include radiographic progression-free survival, overall survival, duration of response, duration of stable disease, and safety. RESULTS: Thirty patients with mCRPC with BRCA1 / 2 mutations were treated with olaparib. The disease control rate was 69% (95% CI, 51 to 81), and the objective response rate was 58% (95% CI, 37 to 77). The median radiographic progression-free survival and the median overall survival were 38.4 (95% CI, 16.3 to 52.1) weeks and 76.4 (95% CI, 49.3 to 106.0) weeks, respectively. Six of 30 (20%) patients experienced grade 3-4 adverse or serious adverse events including anemia, aspiration, decreased WBC count, and fatigue. CONCLUSION: Olaparib has antitumor activity in patients with mCRPC with BRCA1 / 2 mutations and warrants further study to determine how to best integrate it into the standard treatment of patients with BRCA1 / 2 -mutated prostate cancer. Olaparib showed a positive signal of activity in real-world patients w/prostate cancer w/BRCA1 or BRCA2 mutations @ASCO #TAPUR. [ABSTRACT FROM AUTHOR]

BACKGROUND: The treatment for prostate cancer patients with biochemical failure after local therapy remains controversial. Peripheral androgen blockade using a combination of a 5-alpha reductase inhibitor and an antiandrogen may allow control of the prostate-specific antigen (PSA). Because testosterone levels are not suppressed, this approach may be associated with less morbidity than conventional gonadal androgen suppression. METHODS: All patients had undergone previous definitive local therapy and had evidence of a rising PSA >1ng/mL, with no evidence of recurrent disease. Patients received both finasteride, 5 mg orally per day, and flutamide, 250 mg orally 3× a day. Patients were followed for a PSA response and quality of life assessment. RESULTS: Ninety-nine of 101 accrued patients were eligible. A ≥80% PSA decline was seen in 96 (96%) patients. The median time to PSA progression was 85 months. With a median follow-up of 10 years, the median survival time had not been reached, and the 5-year overall survival rate was 87%. Toxicity was mild, with 18 patients stopping for toxicity; 15 had diarrhea, 4 had gynecomastia, and 3 had transaminase elevation. Baseline Functional Assessment of Cancer Therapy Prostate Module and Treatment Outcome Index scores decreased by 5 points each at 6 months after enrollment. CONCLUSIONS: The use of the finasteride/flutamide combination is feasible, and results in PSA declines of ≥80% in 96% of patients with serologic progression after definitive local therapy. There were no unexpected toxicities, and the change in quality of life was mild. Further evaluation of this or a similar regimen in a controlled clinical trial is warranted. Cancer 2012. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

The article presents a study which evaluates the safety and feasibility of radiotherapy after paclitaxel, estramustine phosphate and carboplatin (TEC) plus androgen therapy in previously treated prostate cancer patients. It mentions that patients with localized high-risk prostate cancer were treated with four cycles of paclitaxel in a period of 16 weeks. It affirms that the authors concluded that neoadjuvant chemohormonal therapy with TEC followed by high-dose radiation therapy is safe.

Purpose: A prior report suggested that radical prostatectomy may confer a survival advantage to patients with metastatic castration recurrent prostate cancer. Therefore, a pooled analysis of 9 trials performed by Cancer and Leukemia Group B was done to determine if men with metastatic castration recurrent prostate cancer who underwent prior prostatectomy had improved clinical outcomes, such as overall, prostate specific, progression-free and PSA progression-free survival, than men who did not undergo prior prostatectomy. Materials and Methods: Data from 9 multi-institutional trials performed by Cancer and Leukemia Group B were combined. Eligible patients had progressive prostate cancer during androgen deprivation therapy, Eastern Cooperative Oncology Group performance status 0–2, and adequate hematological, renal and hepatic functions. The proportional hazards model was used to assess the prognostic importance of radical prostatectomy for predicting clinical outcomes. Results: Of 1,238 men 310 (25%) underwent prostatectomy. Median survival was 14.7 (95% CI 12.9–16.7) and 14.5 months (95% CI 13.5–15.7) in men who did and did not undergo prostatectomy, respectively. The HR for death was 1.03 (95% CI 0.90–1.19, p = 0.65) in men with vs without prostatectomy. Conclusions: Prior prostatectomy in men with metastatic castration recurrent prostate cancer who were subsequently enrolled on clinical trials for cancer treatment had similar survival compared to men who did not undergo prior prostatectomy. These data do not support another report suggesting that prior prostatectomy confers a subsequent survival advantage in men with castration recurrent prostate cancer. [Copyright &y& Elsevier]

Purpose: We determined if age is a prognostic factor of clinical outcomes, specifically overall survival, disease-free survival and progression-free survival in men with hormone refractory prostate cancer. Materials and Methods: Data from 8 multi-institutional trials performed by Cancer and Leukemia Group B were combined. Eligible patients had progressive adenocarcinoma of the prostate after androgen ablation, Eastern Cooperative Oncology Group performance status 0 to 2, and adequate hematological, renal and hepatic function. The proportional hazards model stratified by study was used to assess the prognostic importance of age for predicting clinical outcomes. Results: Of 1,194 men 132 (11%) were 50 to 60 years old and 120 (10%) were 80 to 89 years old. Median survival was 12.2 months (95% CI 10.6 to 13.8) in men 50 to 59 years old, 15.9 months (95% CI 14.2 to 17.6) in men 60 to 69 years old, 15.6 months (95% CI 13.8 to 16.9) in men 70 to 79 years old and 8.9 months (95% CI 6.6 to 12.1) in men 80 to 89 years old. Compared to 70 to 79-year-old men the HR for death in octogenarians was 1.3 (95% CI 1.0 to 1.6, p = 0.015). Furthermore, the HR for prostate cancer death in octogenarians was 1.3 (95% CI 1.1 to 1.7, p = 0.010) and in 50 to 59-year-old men it was 1.3 (95% CI 1.0 to 1.6, p = 0.042) compared to men 70 to 79 years old. Black men were at lower risk for death than white men (HR 0.77, 95 CI% 0.65 to 0.92, p = 0.004). Conclusions: Octogenarians and white men are at increased risk for death compared to other men with hormone refractory prostate cancer. [Copyright &y& Elsevier]