African-American men have a higher incidence of prostate cancer and an associated mortality rate than men of other races and ethnicities. Previous studies have identified several biomarkers that can predict aggressive types of prostate cancer, but these have been limited to European-American men and did not focus on ethnicity as an end point. A new study has now investigated the relevance of these biomarkers to aggressive prostate cancer and disease recurrence in African-American men (Yamoah K, et al. J Clin Oncol. 2015;33:2789-2797).
Data were collected from 397 matched patients, consisting of 154 African-American and 243 European-American men with prostate cancer. The participants were identified at 4 institutions and were matched based on their Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) score at diagnosis, all matches within 2 points of one another. The median follow-up time was 39 months.
Only the 20 biomarkers that have previously been reported twice or more to be associated with aggressive prostate cancer were evaluated in this study. To determine an ethnically-dependent association that can predict the risk for pathologic T3 (pT3) disease in an “ethnicity-dependent manner,” the researchers looked for a significant ethnic difference by biomarker interaction odds ratio, with P <.05 predicting the risk for clinicopathologic outcomes.
The use of the Mann-Whitney Wilcoxon test to examine continuous biomarker expression levels showed significant differences in expression by ethnicity in 6 biomarkers—ERG, AMACR, SPINK1, NKX3-1, GOLM1, and androgen receptor. In addition, a logistic regression model used to assess ethnicity differences showed significant difference in 4 biomarkers—ERG, AMACR, SPINK1, and GOLM1.
Furthermore, the results showed that African-American men present with prostate cancer at an earlier age (range, 37-73 years) than European-American men (range, 43-76 years) and are more likely to have triple-negative disease.
According to the investigators, “One of the more striking findings was the ethnic association between pT3 disease and ERG” among African-American men, as well as their increased risk for the triple-negative prostate cancer subtype. These findings indicate that prostate cancer “may arise from different tumor progenitors and/or distinct molecular pathways” among European-American and African-American men.
To date, this is the largest and only study to identify prostate cancer biomarkers that can predict the risk for adverse clinical outcomes in an ethnicity-dependent manner. The results show a physiologic difference in the expression of prostate cancer biomarkers in African-American men versus European-American men. Understanding these ethnic differences can influence the approach to the diagnosis and treatment of African-American men with prostate cancer, and can reduce current differences in outcomes for this patient population.
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Chemotherapy-induced nausea and vomiting (CINV) is a common complication of many cancer treatments in adults and in children. The oral neurokinin-1 (NK1) receptor antagonist aprepitant (Emend) is an effective option for CINV prevention in adult patients who receive emetogenic chemotherapy. However, its safety and efficacy in pediatric patients have not been investigated before, despite the high incidence of CINV events in this patient population. Furthermore, current clinical guidelines have no age-related recommendations for the prevention of CINV in children undergoing moderate or highly emetogenic chemotherapy. A recent study investigated the efficacy and safety of oral aprepitant in pediatric patients with cancer who receive highly emetogenic chemotherapy (Kang HJ, et al. Lancet Oncol. 2015;16:385-394).
This multicenter, randomized, placebo-controlled phase 3 study included 307 patients with cancer aged 6 months to 17 years who received emetogenic chemotherapy between September 2011 and August 2013 in 49 sites in 24 countries. The patients were randomized in a 1:1 manner, based on age and the type of chemotherapy to be used, to aprepitant plus ondansetron (Zofran) or to placebo plus ondansetron, with or without dexamethasone. The study used 2 doses of aprepitant based on the patient’s age—6 months to <12 years and 12 years to 17 years.
The patients in the aprepitant group received aprepitant plus ondansetron on day 1 of chemotherapy, followed by aprepitant alone on days 2 and 3; the control group received placebo plus ondansetron on the first day of chemotherapy, followed by placebo alone on days 2 and 3. Episodes of vomiting and retching and the use of rescue medications were recorded up to 120 hours after the initiation of chemotherapy. The primary efficacy end point was the proportion of patients achieving a complete response (ie, no CINV events or the use of a rescue medication) during the delayed phase, 25 to 120 hours, after the initiation of emetogenic chemotherapy.
Overall, 51% of the patients receiving aprepitant and 26% of the patients receiving placebo achieved a complete response in the delayed phase (P <.001). The median time to the first vomiting episode was 96.3 hours in the aprepitant group compared with 27.5 hours in the control group. After 98 hours, 68% of patients in the aprepitant group and 52% of patients in the control group were free of rescue medication use.
The most common grade 3 or 4 adverse events were febrile neutropenia (15% with aprepitant vs 14% with placebo), anemia (9% vs 17%, respectively), and reduced neutrophils (7% vs 11%, respectively). In addition, 2 patients in the aprepitant group discontinued therapy because of a serious adverse event. No treatment-related deaths were reported.
This study shows that a 3-day regimen of oral aprepitant, in conjunction with ondansetron, with or without the addition of dexamethasone, provides significant benefits for pediatric patients who receive highly emetogenic chemotherapy. Aprepitant was just approved by the FDA for the treatment of this patient population on August 28, 2015.
