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Background: Retrospective analyses of randomized trials suggest that Black men with metastatic castration‐resistant prostate cancer (mCRPC) have longer survival than White men. The authors conducted a prospective study of abiraterone acetate plus prednisone to explore outcomes by race. Methods: This race‐stratified, multicenter study estimated radiographic progression‐free survival (rPFS) in Black and White men with mCRPC. Secondary end points included prostate‐specific antigen (PSA) kinetics, overall survival (OS), and safety. Exploratory analysis included genome‐wide genotyping to identify single nucleotide polymorphisms associated with progression in a model incorporating genetic ancestry. One hundred patients self‐identified as White (n = 50) or Black (n = 50) were enrolled. Eligibility criteria were modified to facilitate the enrollment of individual Black patients. Results: The median rPFS for Black and White patients was 16.6 and 16.8 months, respectively; their times to PSA progression (TTP) were 16.6 and 11.5 months, respectively; and their OS was 35.9 and 35.7 months, respectively. Estimated rates of PSA decline by ≥50% in Black and White patients were 74% and 66%, respectively; and PSA declines to <0.2 ng/mL were 26% and 10%, respectively. Rates of grade 3 and 4 hypertension, hypokalemia, and hyperglycemia were higher in Black men. Conclusions: Multicenter prospective studies by race are feasible in men with mCRPC but require less restrictive eligibility. Despite higher comorbidity rates, Black patients demonstrated rPFS and OS similar to those of White patients and trended toward greater TTP and PSA declines, consistent with retrospective reports. Importantly, Black men may have higher side‐effect rates than White men. This exploratory genome‐wide analysis of TTP identified a possible candidate marker of ancestry‐dependent treatment outcomes. This is the first prospective, race‐stratified study in advanced prostate cancer demonstrating important trends in outcomes previously only observed in retrospective reports. These results demonstrate the feasibility of this approach in a multicenter setting and establish important preliminary data with regard to differences in toxicity profiles and predictive biomarkers by race. [ABSTRACT FROM AUTHOR]

BACKGROUND Bevacizumab is associated with an increased risk of arterial thromboembolism (ATE); however, its effect on venous thromboembolism (VTE) remains controversial. Scant data exist on the factors that increase the risk of ATE/VTE in patients with prostate cancer. The authors investigated the association of bevacizumab treatment and clinical factors with ATE/VTE risk in patients who were treated on Cancer and Leukemia Group B (CALGB) trial 90401. METHODS Patients with metastatic, castration-resistant prostate cancer were randomized to receive docetaxel and prednisone with or without bevacizumab once every 21 days. Cycle-to-event Cox regression models were used to investigate the association of bevacizumab with the incidence of grade 3 or greater (≥3) ATE and VTE. Age, prior ATE/VTE, baseline antiplatelet/anticoagulant use, and VTE risk score (based on leukocyte count, hemoglobin, platelet count, body mass index, and tumor location) were evaluated in univariate and multivariable analyses. RESULTS Of 1008 randomized patients, the odds of experiencing grade ≥3 ATE were significantly greater in those who received bevacizumab compared with those who received placebo (odds ratio, 2.79; P = .02), whereas an opposite trend was noted for grade ≥3 VTE (odds ratio, 0.60; P = .08). In the multivariable analysis, bevacizumab treatment (hazard ratio [HR], 3.00; P = .01) and age (HR, 1.06; P = .02) were significantly associated with the risk of ATE; whereas age (HR, 1.05; P = .01) and VTE risk score (HR, 1.83; P = .03) were significantly associated with the risk of VTE. CONCLUSIONS Bevacizumab was significantly associated with a greater risk of ATE in patients with metastatic, castration-resistant prostate cancer, but it was not significantly associated with the risk of VTE. Understanding clinical factors that increase the risk for experiencing ATE/VTE is essential to mitigate the risks and reduce the burden of these prevalent complications in cancer care. Cancer 2015;121:1025-1031. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND The current study was conducted to investigate the dependence between progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) and to explore whether PFS can be used as an intermediate endpoint of OS in this patient population. METHODS A total of 1381 patients from 2 prospective phase 3 trials (Cancer and Leukemia Group B [CALGB] 90206 and AVOREN) of interferon-alpha with or without bevacizumab were analyzed. Both trials recruited previously untreated patients with clear cell mRCC with an Eastern Cooperative Oncology Group performance status of 0 to 2; adequate bone marrow, hepatic, cardiac, and renal function; and controlled blood pressure. The CALGB study served as the training data set, and the AVOREN study served as the testing data set. The dependence between PFS and OS was investigated using the Kendall tau for bivariate time-to-event endpoints. RESULTS In the training data set, the median OS times among patients who experienced progressive disease at 3 months or 6 months were 6 months and 8 months, respectively, compared with 25 months and 30 months, respectively, ( P < .001) in patients who did not develop disease progress. The adjusted hazard ratios (HR) were 2.6 ( P < .0001) and 2.8 ( P < .0001), respectively, for patients who did and did not progress at 3 months or 6 months. The dependence between PFS and OS was 0.53. These associations were confirmed in the testing data set. CONCLUSIONS In patients with mRCC who were treated with interferon-alpha with or without bevacizumab, the PFS at 3 months and 6 months was found to be predictive of OS. A high dependence between PFS and OS was observed, suggesting that PFS may be used as a surrogate endpoint for OS. Although this is a novel observation for RCC, these findings require validation in patients with mRCC who are treated with other targeted agents. Cancer 2014;120:52-60. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Preliminary data suggest a potential decreased benefit of docetaxel in patients with metastatic, castration-resistant prostate cancer (mCRPC) who previously received abiraterone acetate, a novel androgen synthesis inhibitor (ASI). Cancer and Leukemia Group B (CALGB) trial 90401 (Alliance), a phase 3 trial in patients with mCRPC who received docetaxel-based chemotherapy, offered the opportunity to evaluate effect of prior ketoconazole, an earlier generation ASI, on clinical outcomes after docetaxel.Methods: In CALGB trial 90401, 1050 men with chemotherapy-naive mCRPC were randomized to receive treatment with docetaxel and prednisone that included either bevacizumab or placebo. In total, 1005 men (96%) had data available regarding prior ketoconazole therapy. The observed effects of prior ketoconazole on overall survival (OS), progression-free survival (PFS), prostate-specific antigen (PSA) decline, and the objective response rate (ORR) were assessed using proportional hazards and Poisson regression methods adjusted for validated prognostic factors and treatment arm.Results: Baseline characteristics between patients who did (N=277) and did not (N=728) receive prior ketoconazole therapy were similar. There were no statistically significant differences between patients who did and those who did not receive prior ketoconazole therapy with respect to OS (median OS, 21.1 months vs 22.3 months, respectively; stratified log-rank P=.635), PFS (median PFS, 8.1 months vs 8.6 months, respectively; stratified log-rank P=.342), the proportion achieving a decline ≥ 50% in PSA (61% vs 66%, respectively; relative risk, 1.09; adjusted P=.129), or ORR (39% vs 43%, respectively; relative risk, 1.11; adjusted P=.366).Conclusions: As measured by OS, PFS, PSA, and the ORR, there was no evidence that prior treatment with ketoconazole had an impact on the clinical outcomes of patients with mCRPC who received subsequent docetaxel-based therapy. The current results highlight the need for prospective studies to assess for potential cross-resistance with novel ASIs and to define the optimal sequence of therapy in mCRPC. [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]

BACKGROUND: Combined transperineal prostate brachytherapy and external beam radiation therapy (EBRT) is widely used for treatment of prostate cancer. Long-term efficacy and toxicity results of a multicenter phase 2 trial assessing combination of EBRT and transperineal prostate brachytherapy boost with androgen deprivation therapy (ADT) for intermediate-risk prostate cancer are presented. METHODS: Intermediate-risk patients per Memorial Sloan-Kettering Cancer Center/National Comprehensive Cancer Network criteria received 6 months of ADT, and 45 grays (Gy) EBRT to the prostate and seminal vesicles, followed by transperineal prostate brachytherapy with I125 (100 Gy) or Pd103 (90 Gy). Toxicity was graded using the National Cancer Institute Common Toxicity Criteria version 2 and Radiation Therapy Oncology Group late radiation morbidity scoring systems. Disease-free survival (DFS) was defined as time from enrollment to progression (biochemical, local, distant, or prostate cancer death). In addition to the protocol definition of biochemical failure (3 consecutive prostate-specific antigen rises >1.0 ng/mL after 18 months from treatment start), the 1997 American Society for Therapeutic Radiology and Oncology (ASTRO) consensus and Phoenix definitions were also assessed in defining DFS. The Kaplan-Meier method was used to estimate DFS and overall survival. RESULTS: Sixty-one of 63 enrolled patients were eligible. Median follow-up was 73 months. Late grade 2 and 3 toxicity, excluding sexual dysfunction, occurred in 20% and 3% of patients. Six-year DFS applying the protocol definition, 1997 ASTRO consensus, and Phoenix definitions was 87.1%, 75.1%, and 84.9%. Six deaths occurred; only 1 was attributed to prostate cancer. Six-year overall survival was 96.1%. CONCLUSIONS: In a cooperative setting, combination of EBRT and transperineal prostate brachytherapy boost plus ADT resulted in excellent DFS with acceptable late toxicity for patients with intermediate-risk prostate cancer. Cancer 2011;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The use of docetaxel prolongs survival for patients with castrate-resistant prostate cancer (CRPC). Inhibition of vascular endothelial growth factor (VEGF) with bevacizumab may further enhance the antitumor effect of docetaxel and estramustine in patients with CRPC. METHODS: This cooperative group trial enrolled men with CRPC. Patients received oral estramustine 280 mg 3 times daily on Days 1 through 5 of every cycle plus 70 mg/m² docetaxel and 15 mg/kg bevacizumab on Day 2 every 3 weeks. Prostate-specific antigen (PSA) values were monitored every cycle, and imaging studies were obtained every 3 cycles. The primary endpoint was progression-free survival (PFS), and the secondary objectives were safety, PSA decline, measurable disease response, and overall survival. RESULTS: Seventy-nine patients were enrolled; and 77 patients received a median of 8 cycles and were evaluable. A 50% PSA decline was observed in 58 patients (75%). Twenty-three of 39 patients with measurable disease had a partial response (59%). The median PFS was 8 months, and the overall median survival was 24 months. Neutropenia without fever (69%), fatigue (25%), and thrombosis/emboli (9%) were the most common severe toxicities. Twenty-four of 77 patients were removed from protocol treatment because of disease progression, 35 of 77 patients were removed because of a physician or patient decision, and 15 patients were removed secondary to toxicity. CONCLUSIONS: The combination of docetaxel, estramustine, and bevacizumab was tolerable but complicated by toxicity. Although the endpoint of PFS did not meet the desired level, encouraging antitumor activity and overall survival were observed. Further phase 3 evaluation of the role of bevacizumab in CRPC is ongoing. [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.

The article focuses on a study that aims to evaluate the correlation between an elevated body mass index (BMI) and clinical outcomes in patients with metastatic, castration-recurrent prostate cancer (CRPC). It cites the association between obesity and the risk of certain malignancies such as colon cancer and renal cell carcinoma. It concludes that patients with metastatic CRPC, obesity appears to have a protective effect against overall mortality and prostate cancer-specific mortality.

A letter to the editor is presented in response to the article "Progression-free survival: does a correlation with survival justify its role as a surrogate clinical endpoint?" by A. Becker and colleagues in a 2014 issue.