Successful recruitment of healthy African American men to genomic studies from high-volume community health fairs: implications for future genomic research in minority populations.

BACKGROUND: Study of genomic data obtained from patient biospecimens is frequent in research of subjects with prostate and other epithelial malignancies. Understanding of the characteristics of healthy men who participate in genomic research is limited. METHODS: Patients were identified through the Prostate Cancer Genetic Risk Evaluation of SNPs Study and the Indiana University Cancer Biomarker Study, 2 population-based biomarker and cohort studies. Between 2006 and 2010, healthy Caucasian (n = 774) and healthy African American (n = 381) men were recruited and enrolled at high-volume free community health fairs. Each participant completed a demographic questionnaire and provided a blood sample for genomic research investigations. Frequency differences between demographic features of healthy African American and Caucasian men were compared and analyzed by 2-sample t test and multivariate logistic regression after adjusting potential confounding variables with significance at the P < .05 level. Features examined included: age, body mass index (BMI), income, education, marital status, tobacco, alcohol, family history, prostate-specific antigen (PSA) level, and prior prostate cancer screening history. RESULTS: Significant differences between healthy Caucasian and African American men participating in genomic research included: marital status (married, 69% Caucasian vs 46% African American, P< < .001), mean age (years, 58 Caucasian vs 54 African American, P < .001), mean BMI (kg/m(2), 30.9 Caucasian vs 32.3 African American, P = .004), annual income (P = .038), education (P = .002), and mean PSA (ng/mL, 1.2 Caucasian vs 2.0 African American, P = .005). CONCLUSIONS: Significant demographic differences exist between healthy Caucasian and African American men choosing to participate in genomic research. These differences may be important in designing genomic research study recruitment strategies.

Phase II trial of cisplatin, gemcitabine, and bevacizumab as first-line therapy for metastatic urothelial carcinoma: Hoosier Oncology Group GU 04-75.

PURPOSE: Novel approaches are needed for patients with metastatic urothelial cancer (UC). This trial assessed the efficacy and toxicity of bevacizumab in combination with cisplatin and gemcitabine (CGB) as first-line treatment for patients with metastatic UC. PATIENTS AND METHODS: Chemotherapy-naive patients with metastatic or unresectable UC received cisplatin 70 mg/m(2) on day 1, gemcitabine 1,000 to 1,250 mg/m(2) on days 1 and 8, and bevacizumab 15 mg/kg on day 1, every 21 days. RESULTS: Forty-three patients with performance status of 0 (n = 26) or 1 (n = 17) and median age of 66 years were evaluable for toxicity and response. Grade 3 to 4 hematologic toxicity included neutropenia (35%), thrombocytopenia (12%), anemia (12%), and neutropenic fever (2%). Grade 3 to 5 nonhematologic toxicity included deep vein thrombosis/pulmonary embolism (21%), hemorrhage (7%), cardiac (7%), hypertension (5%), and proteinuria (2%). Three treatment-related deaths (CNS hemorrhage, sudden cardiac death, and aortic dissection) were observed. Best response by Response Evaluation Criteria in Solid Tumors was complete response in eight patients (19%) and partial response in 23 patients (53%), for an overall response rate of 72%. Stable disease lasting ≥ 12 weeks occurred in four patients (9%), and progressive disease occurred in six patients (14%). With a median follow-up of 27.2 months (range, 3.5 to 40.9 months), median progression-free survival (PFS) was 8.2 months (95% CI, 6.8 to 10.3 months) with a median overall survival (OS) time of 19.1 months (95% CI, 12.4 to 22.7 months). The study-defined goal of 50% improvement in PFS was not met. CONCLUSION: CGB demonstrates promising OS and antiangiogenic treatment-related toxicities in the phase II setting of metastatic UC. The full risk/benefit profile of CGB in patients with metastatic UC will be determined by an ongoing phase III intergroup trial.

A phase I dose escalation and pharmacokinetic study of vatalanib (PTK787/ZK 222584) in combination with paclitaxel in patients with advanced solid tumors.

PURPOSE: To define the maximum-tolerated dose (MTD) for weekly paclitaxel administered in combination with daily vatalanib (PTK787/ZK 222584, PTK/ZK) and assess for a drug-drug interaction. METHODS: Patients were treated with escalating doses of weekly paclitaxel (75-85 mg/m(2)), and daily PTK/ZK (250-1,000 mg). During the first cycle only, paclitaxel was given on days 1 and 15, and PTK/ZK on days 3-28. Pharmacokinetic studies were conducted on cycle 1 days 1 and 15 for paclitaxel, and on cycle 1 day 15 for PTK/ZK. Therapy was given until disease progression. RESULTS: Twenty-seven patients were accrued to four dose levels. Two of five patients treated with paclitaxel 85 mg/m(2) and PTK/ZK 1,000 mg had Grade 3 transaminase elevation as dose-limiting toxicity. Paired PK analyses demonstrated a significant increase in paclitaxel clearance on day 15 (p = 0.006). Activity included one partial response and 11 patients with stable disease > or =4 months, including patients previously treated with paclitaxel. CONCLUSIONS: The MTD for weekly paclitaxel plus daily PTK/ZK is 75 mg/m(2) and 750 mg. PK analysis revealed a significant drug-drug interaction, with an increase in paclitaxel clearance. This combination was well tolerated with evidence of anti-cancer activity and provides guidance for phase 2 planning.