Multi-institutional phase I study of low-dose ultra-fractionated radiotherapy as a chemosensitizer for gemcitabine and erlotinib in patients with locally advanced or limited metastatic pancreatic cancer.

PURPOSE: Gemcitabine (G) has been shown to sensitize pancreatic cancer to radiotherapy but requires lower doses of G and thus delays aggressive systemic treatment, potentially leading to distant failure. We initiated a phase I trial combining ultra-fractionated low-dose radiotherapy with full dose G and erlotinib in the treatment of patients with advanced pancreatic cancer. METHODS: Patients with locally advanced or metastatic pancreatic cancer confined to the abdomen and an ECOG performance status (PS) of 0-1 who had received 0-1 prior regimens (without G or E) and no prior radiotherapy were eligible. Patients were treated in 21 day cycles with G IV days 1 & 8, E once PO QD, and twice daily RT fractions separated by at least 4h on days 1, 2, 8, and 9. Whole abdominal RT fields were used. Primary endpoint was to define dose limiting toxicity (DLT) and the maximum tolerated dose (MTD). RESULTS: 27 patients (median age 64 years and 15 male) were enrolled between 11/24/08 and 4/12/12. 1 patient withdrew consent prior to receiving any protocol therapy. 17 patients had a PS of 1. The majority of patients were stage IV. One DLT was noted out of 7 patients at dose level (DL) 1. Subsequently no DLTs were noted in 3 patients each enrolled at DL2-4 or 11 patients in the expansion cohort. The majority of grade 3 toxicities were hematologic with 1 grade 5 bowel perforation in dose level 1 in cycle 4. Best response in 24 evaluable patients: PR (8), stable (15), PD 1. Median survival for the entire group was 9.1 months. CONCLUSION: This phase I study combining low-dose ultra-fractionated RT as a sensitizer to full dose G plus E was well tolerated with encouraging efficacy. This represents a novel strategy worthy of further investigation in advanced pancreatic cancer patients.

Determining the health benefits of poultry industry compliance measures: the case of campylobacteriosis regulation in New Zealand.

I undertake a cost benefit analysis of the food safety regulation of production of poultry for the New Zealand domestic market and the reduction in foodborne illness following this. I take a societal perspective to demonstrate that regulation brings both benefits and costs. I derive a cost of illness (COI) estimate of foodborne campylobacteriosis from three previous studies. I apply a cost benefit analysis (CBA) to this estimate, combined with the cost data supplied by industry and the regulator. The benefit:cost ratio was remarkable, showing a good return from the combined efforts of industry and the regulator in reduction of campylobacteriosis; in dollar terms a gain of at least $57.4 million annually. In summary the study demonstrates the high value to the New Zealand economy of investment in food safety compliance at the primary industry level.

Geographic divergence of bovine and human Shiga toxin­producing Escherichia coli O157:H7 genotypes, New Zealand.

Shiga toxin-producing Escherichia coli (STEC)O157:H7 is a zoonotic pathogen of public health concern worldwide. To compare the local and large-scale geographic distributions of genotypes of STEC O157:H7 isolates obtained from various bovine and human sources during 2008­2011, we used pulsed-field gel electrophoresis and Shiga toxin­encoding bacteriophage insertion (SBI) typing. Using multivariate methods, we compared isolates from the North and South Islands of New Zealand with isolates from Australia and the United States. The STEC O157:H7 population structure differed substantially between the 2 islands and showed evidence of finer scale spatial structuring, which is consistent with highly localized transmission rather than disseminated foodborne outbreaks. The distribution of SBI types differed markedly among isolates from New Zealand, Australia, and the United States. Our findings also provide evidence for the historic introduction into New Zealand of a subset of globally circulating STEC O157:H7 strains that have continued to evolve and be transmitted locally between cattle and humans.