Colonoscopy Findings in HIV-Infected Men and Women from an Urban U.S. Cohort Compared with Non-HIV-Infected Men and Women.

INTRODUCTION: As HIV-infected patients live longer, non-AIDS-defining cancers are now a major cause of morbidity and mortality. The purpose of this study was to compare the prevalence, type, and location of colorectal neoplastic lesions found on colonoscopy in HIV-infected patients from an urban U.S. cohort with non-HIV-infected patients. METHODS: We collected clinical data and colonoscopy findings on 263 HIV-infected patients matched with 657 non-HIV-infected patients on age, race, and sex. Frequency distributions and descriptive statistics were used to characterize the study population. The primary exposure was HIV infection, and the primary outcome was any adenoma or adenocarcinoma. Logistic regression models were used to estimate odds ratios with 95% confidence intervals (CIs). RESULTS: Participants were primarily African American and 40% were women. HIV-infected patients were less likely to have any neoplastic lesions (21.3% vs. 27.7%, p < .05), adenoma (20.5% vs. 27.1%, p = .04), tubular adenomas >10 mm (0.4% vs. 2.9%, p = .02), and serrated adenomas (0.0% vs.2.6%, p = <.01). There was a nonsignificant increased prevalence of adenocarcinoma in HIV-infected individuals compared with non-HIV-infected individuals (1.5% vs. 0.8%, p = .29). The lower prevalence of any adenoma remained after controlling for age, sex, smoking status, body-mass index, and diabetes mellitus [adjusted odds ratio (aOR), 0.61; 95% CI, 0.43-0.88]. HIV-infected patients had a lower prevalence of colorectal neoplastic lesions, including high-risk adenomas, than non-HIV-infected patients. CONCLUSIONS: Our findings suggest that HIV infection in a primarily African American population is associated with a lower prevalence of colorectal adenomas, but not adenocarcinoma, found by colonoscopy.

A phase II trial of tamoxifen and bortezomib in patients with recurrent malignant gliomas.

NF-kB inhibition by bortezomib enhances tamoxifen-induced apoptosis in preclinical glioma models. We conducted a single institution, phase II trial to evaluate efficacy and safety of high dose tamoxifen with bortezomib in adults with recurrent malignant gliomas. The primary endpoint was radiographic response. Concurrent enzyme inducing anticonvulsants and grade ≥2 peripheral neuropathy were exclusion criteria. Patients received tamoxifen (120 mg PO twice daily) and bortezomib (1.3 mg/m2 IV on days 3, 6, 10, 13, 24, 27, 31, and 34) per 6-week cycles. We enrolled 42 patients with anaplastic gliomas (AGs, n = 12) and glioblastomas (GBMs, n = 30), 32 males and 10 females. Median age was 38 years (range 22-65) and 48 years (range 19-68) for AGs and GBMs, respectively. median karnofsky performance status was 90% (range 70-100) for AGs and 80% (range 60-100) for GBMs. Median prior therapies was 3, ranging 1-7. Grade ≥3 toxicities included lymphopenia (4/42), hypophosphatemia (3/42), thromobocytopenia (2/42), and 1/42 with hyponatremia, headache, dyspnea, or DVT. One patient withdrew consent, two were removed for toxicity, and all others discontinued for progression. Among 40 patients evaluable for response, only one achieved stable disease for 3 months; all others progressed rapidly. For AGs and GBMs respectively, median progression-free survival was 5.9 and 5.7 weeks and median overall survival was 25.6 and 14.7 weeks. The study was closed due to poor accrual and therapeutic futility. Combination tamoxifen and bortezomib has no activity in recurrent malignant gliomas. Poor penetration across blood brain barrier of bortezomib likely limited efficacy.