The addition of algenpantucel-L to standard adjuvant therapy for resected pancreatic cancer may improve survival. A multi-institutional, phase 3 study is ongoing (ClinicalTrials.gov identifier, NCT01072981).

Objective: Clinical and epidemiological research suggest that bone mineral density (BMD) in women is shaped by various reproductive factors such as parity and lactation patterns. However, the extent of these effects on BMD remains unclear because of contradictory findings and a focus on industrialized populations. Because fertility patterns in these groups are vastly different than those of women from non‐Western, subsistence populations, our current understanding of the reproductive effects on skeletal health is incomplete. Using a life history perspective, this study examines the relationship between reproductive factors and bone density among women from the Indigenous Shuar population, an Amazonian Ecuadorian forager‐horticulturalist group. Methods: This preliminary, cross‐sectional study included 130 premenopausal and postmenopausal women (14–86 years old) from the Morona‐Santiago region of Ecuador. Anthropometrics were recorded, as was estimated BMD using a calcaneal ultrasonometer. A reproductive history questionnaire was administered that included questions regarding menarche, parity, lactation patterns, and menopause. Results: Among postmenopausal women, early menarche and greater stature were significantly associated with higher bone density values. Among premenopausal women, few significant relationships between bone values and reproductive variables were documented; effects of lactation appeared to be transient and restored following weaning. Conclusions: Although preliminary and not based on longitudinal data, these findings suggest that the effects of reproduction are transient as the system of calcium homeostasis in premenopausal women efficiently restores the bone loss that results from metabolically active reproductive states. Further, this research suggests that the timing of early life history events may canalize bone density phenotype. Am. J. Hum. Biol., 2012. © 2012 Wiley Periodicals, Inc.

Purpose Inhibitors of DNA (cytosine-5)-methyltransferases (DNMT) are active antineoplastic agents. We conducted the first-in-human phase I trial of 5-fluoro-2′-deoxycytidine (FdCyd), a DNMT inhibitor stable in aqueous solution, in patients with advanced solid tumors. Objectives were to establish the safety, maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of FdCyd + tetrahydrouridine (THU). Methods FdCyd + THU were administered by 3 h IV infusion on days 1–5 every 3 weeks, or days 1–5 and 8–12 every 4 weeks. FdCyd was administered IV with a fixed 350 mg/m2/day dose of THU to inhibit deamination of FdCyd. Pharmacokinetics of FdCyd, downstream metabolites and THU were assessed by LC–MS/MS. RBC γ-globin expression was evaluated as a pharmacodynamics biomarker. Results Patients were enrolled on the 3-week schedule at doses up to 80 mg/m2/day without dose-limiting toxicity (DLT) prior to transitioning to the 4-week schedule, which resulted in an MTD of 134 mg/m2/day; one of six patients had a first-cycle DLT (grade 3 colitis). FdCyd ≥40 mg/m2/day produced peak plasma concentrations >1 μM. Although there was inter-patient variability, γ-globin mRNA increased during the first two treatment cycles. One refractory breast cancer patient experienced a partial response (PR) of >90 % decrease in tumor size, lasting over a year. Conclusions The MTD was established at 134 mg/m2 FdCyd + 350 mg/m2 THU days 1–5 and 8–12 every 4 weeks. Based on toxicities observed over multiple cycles, good plasma exposures, and the sustained PR observed at 67 mg/m2/day, the phase II dose for our ongoing multi-histology trial is 100 mg/m2/day FdCyd with 350 mg/m2/day THU.

Emerging technologies have greatly expanded our ability to detect, characterize, and treat colorectal cancer. The Coalition of Cancer Cooperative Groups convened a multidisciplinary panel, the Scientific Leadership Council in GI cancer, to discuss and advise on the priorities and opportunities to advance current and future approaches into the clinical arena to impact most rapidly the morbidity and mortality from this disease. The Council's recommendations for research priorities are the result of engagement of community and academic oncologists, patient advocacy groups, and other stakeholders including the pharmaceutical industry and governmental agencies. We detail some key prospects for investigation in the areas of colon cancer detection, prevention, and surgical and medical management. Many are in early or definitive clinical trials, and a focus on rapid accrual is urged. The implementation of biology-directed laboratory investigations, both in association with ongoing clinical trials and as a separate developmental strategy for targeted therapies, is supported as the route to individualized therapy.