The American Veterinary Medical Association recently honored Colorado State University veterinarian Dr. Anthony Simon Turner with the Lifetime Excellence in Research Award. The award recognizes achievement in veterinary research.

Turner has been a member of the College of Veterinary Medicine and Biomedical Sciences faculty since 1977. Using the biological changes in ovariectomized sheep to mimic those seen in postmenopausal women, Turner’s early research studied osteoporosis — decreased bone density — and hot flashes. Osteoporosis, bone density loss and bone fractures are common among the elderly, occurring in about 20 percent of people older than 70.

In 1997, in collaboration with Dr. Clint Rubin, State University of New York, Stony Brook, Turner’s research results gained international attention by showing that the bone density in a sheep’s hind legs increased when they were subjected to a very low force delivered at high frequency. This technology is now available to improve bone density in women.

In other studies in collaboration with human orthopedic surgeons, Turner’s lab pioneered a knee prosthesis designed to replace cancerous bone, providing extra stability compared with traditional implants, minimizing the likelihood of a limb amputation. This custom-fit prosthesis is marketed by an orthopedic company and has been used in more than 400 human patients, giving new hope and an alternative to people facing potential limb amputation.

His current research is studying new surgical techniques for spine fusion, aimed at improving the success rate in humans with low back pain. He is also researching new techniques for rotator cuff surgery.

Turner is a professor in the Department of Clinical Sciences. He is a diplomate of the American College of Veterinary Surgeons, is on the review board of the Veterinary Comparative Orthopedics and Traumatology, and is a consultant editor for Veterinary Clinics of North America: Equine Practice. In 2001 he was inducted in the Glover Gallery for distinguished alumni and faculty at CSU.

Source
Colorado State University

• Explain to interested patients that diarrhea appears to be a significant side effect related to the action of the investigational drug ipilimumab against melanoma.
• Caution patients that ipilimumab is not FDA approved for any indication.

Prophylactic corticosteroid treatment may not prevent moderate to severe diarrhea reactions with the novel monoclonal antibody ipilimumab for advanced melanoma, researchers found.

During ipilimumab treatment, grade 2 or higher diarrhea adverse events were just as common with budesonide (Entocort EC) as with placebo (32.7% versus 35.0%, P=NS), according to Jeffrey Weber, MD, PhD, of the Moffitt Cancer Center in Tampa, Fla., and colleagues.

Although the phase II trial failed, the results provided further evidence for “impressive” survival rates with ipilimumab in both groups, the researchers wrote online ahead of print in Clinical Cancer Research.

Overall survival averaged 17.7 to 19.3 months with the experimental agent compared with roughly six to nine months with standard dacarbazine (DTIC-Dome) treatment seen in prior trials.

Estimated one-year survival was 55.9% to 62.4% with ipilimumab compared with 25% to 44% with chemotherapy and immunotherapy in prior studies.

Ipilimumab, a fully human monoclonal antibody directed against CTL antigen-4 (CTLA-4), is a key negative regulator of the T-cell immune response, and preclinical animal studies have shown that blocking CTLA-4 enhances adaptive immune responses.

It also induces inflammatory adverse events, typically involving the GI tract or the skin.

To see if the oral corticosteroid budesonide — used to reduce GI inflammation in Crohn’s disease — could prevent these reactions, Weber’s group randomized 115 previously treated and treatment-naive patients with unresectable stage 3 or 4 melanoma to open-label ipilimumab (10 mg/kg every three weeks for four doses) plus daily blinded budesonide or placebo.

But after 16 weeks of treatment, prophylactic budesonide showed little benefit.

Overall adverse event rates were similar between treatment groups, with no GI or colonic perforations in either group but nearly all patients having some drug-related adverse events (90% with budesonide versus 95% with placebo).

Grades 3 and 4 immune-related adverse event rates were 29% and 12%, respectively with budesonide and 26% and 12% with placebo.

Notably, the immune-related adverse events appeared related to disease response or control. Partial or complete response or stable disease rates were:

• 46% to 59% in those with grade 3 or 4 events
• 26% to 27% among those with grade 1 or 2 events
• No objective responses and only one stable disease case among those without an immune-related event

Partial or complete response was the best overall response for 12.1% of budesonide-treated patients and 15.8% of placebo-treated patients.

Adding stable disease as an outcome, the response rates were 31.0% versus 35.1%.

Whereas tumor growth or new lesions usually mark treatment failure in advanced melanoma, the researchers reported two new patterns of clinical activity: “reduction in total tumor burden after the appearance of new lesions and/or response after initial increase in total tumor burden.”

Based on these patterns seen in ipilimumab trials, they recommended that progressive disease be confirmed radiologically at least four weeks later. “New efficacy criteria … may be required to more accurately describe the clinical benefit of ipilimumab,” they wrote.