Phase I clinical evaluation of carboplatin in tumor-bearing cats: a Veterinary Cooperative Oncology Group study.

BACKGROUND: The dosage of carboplatin in cats has been reported anecdotally and experimentally in non-tumor-bearing cats, but the dosage for carboplatin treatment in tumor-bearing cats has yet to be defined in a prospective clinical trial. PURPOSE: To determine the maximally tolerated dose (MTD) and dose-limiting toxicosis (DLT) of carboplatin in tumor-bearing cats. CATS: Fifty-nine cats with measurable solid tumors. METHODS: The starting dose of carboplatin was 160 mg/m(2) of body surface area IV. Doses were increased by 20 mg/m(2) in cohorts of 3-14 cats until the MTD was reached. RESULTS: The 59 cats entered into this multi-institutional phase I study received 1 or more doses of carboplatin at various dosages and were evaluated for toxicity, response to treatment, or both. The MTD was 240 mg/m(2) and neutropenia was the DLT. For the 1st cycle of treatment in 44 cats evaluated for neutropenia, 6 episodes of grade 3 or greater neutropenia occurred on days 7 (n=1), 14 (n=4), and 21 (n=1). There was no evidence of drug-induced nephrotoxicosis or pulmonary edema. Preliminary evidence of antitumor activity was observed in 7 of 59 (11.9%; 95% CI, 5.6-22.8%) cats evaluated for response to treatment. There was 1 complete response (cutaneous hemangiosarcoma) and 6 partial responses (4 injection site sarcomas, 1 oral squamous cell carcinoma, 1 lymphoma). Responses were of short duration (median, 42 days; range, 7-168 days). CONCLUSIONS AND CLINICAL IMPORTANCE: The dose of carboplatin recommended to treat tumor-bearing cats is 240 mg/m(2) IV every 3-4 weeks.

Effects of 9,10 anthraquinone on ruminal fermentation, total-tract digestion, and blood metabolite concentrations in sheep.

The objective of this study was to evaluate the effects of adding 9,10 anthraquinone, a known inhibitor of methanogenesis and sulfate reduction, on blood metabolites, digestibility, and distribution of gas in sheep. In all experiments, we fed a complete pelleted diet that contained 17.5% crude protein and 24.5% acid detergent fiber. In an 8-wk study, feeding up to 66 ppm (dry matter basis) of 9,10 anthraquinone had no adverse effects on blood metabolites including indicators of normal enzyme function, mineral concentrations, and hematological measurements. Feeding 9,10 anthraquinone had no effect on average daily gain, although sheep fed a diet containing 66 ppm of 9,10 anthraquinone numerically gained the least weight. The ruminal molar proportions of acetic acid were decreased (P < 0.05) and the molar proportions of propionic acid were increased (P < 0.05) in sheep fed 1.5 and 66 ppm 9,10 anthraquinone when compared to those fed an unsupplemented diet. In a digestion trial, 9,10 anthraquinone (33 and 66 ppm) had no effect on the apparent digestion of nutrients in the total gastrointestinal tract. In a metabolism study, ruminal gasses were collected by rumenocentesis and analyzed for methane and hydrogen concentrations. Feeding 500 ppm of 9,10 anthraquinone to sheep resulted in a decrease (P < 0.07) in the concentration of methane, but an increase (P < 0.05) in hydrogen concentration of ruminal gas throughout the 19 d of feeding. There was no indication of ruminal adaptation throughout this time. These results are the first to show that 9,10 anthraquinone can partially inhibit in vivo rumen methanogenesis, which supports previous in vitro findings. In addition, at the concentrations used in this study, 9,10 anthraquinone was not toxic to ruminants.

Effects of dietary protein on restrict-fed broiler breeder pullets during a coccidial challenge.

In each of two experiments with young, feed-restricted broiler breeder pullets, the effects of differences in dietary protein intake on intestinal development and growth were studied. All pullets were restrict-fed either a 15 or 19% CP diet to see whether differences in dietary protein would influence intestinal growth in the face of controlled exposure to coccidiosis. In each experiment, pullets were vaccinated with one of three dilutions of Coccivac (control, 1X, 4X), each level representing a different proportion of the manufacturers' suggested dosage level. Experiment 1 was conducted in battery cages with wire floors, and no infection was established, most likely because of a lack of oocyst recycling. The pullets that were restrict-fed the 19% CP diet had a significantly heavier Pectoralis major breast muscle weight at 14 and 21 d postvaccination (PV) and heavier BW at 21 d PV. Experiment 2 was conducted in floor pens with litter. In this experiment, coccidiosis was successfully established as coccidial oocysts invaded the mucosal cells of the villi in the upper small intestine. Pullets fed the 19% CP diet had significantly heavier BW at 14, 28, and 35 d of age. There were, however, no significant effects caused by level of dietary protein or vaccination dose on intestinal development (villus height and crypt depth). In conclusion, mild coccidial infections induced via the administration of commercial anticoccidial vaccines do not warrant changes in dietary protein during the onset of feed restriction in young broiler breeder pullets.

Effects of dietary protein and strain on the growth of broiler breeder pullets from zero to five weeks of age.

In a series of four experiments, the effects of differences in dietary protein intake on BW, skeletal growth and the weight of the Pectoralis major muscle was studied in Hubbard Standard and Hubbard Hi-Y broiler breeder pullets. In Experiment 1, pullets were fed diets with either 15, 17, or 19% CP from 1 to 21 d. There was a linear increase in BW gain and feed consumption with each increase in CP and Hubbard Standard pullets consumed significantly more feed than Hubbard Hi-Y pullets. From 21 to 34 d, pullets were subjected to feed restriction every day (ED) or every-other-day (EOD). On Day 35, pullets were given ad libitum access to feed and ED-restricted pullets consumed significantly more feed than EOD-restricted pullets through 3.5 h postfeeding. In Experiment (Exp.) 2, pullets were fed the 19% CP diet for approximately 14 d (300 g) or 20 d (600 g) before being switched to the 15% CP diet. In Experiment 3, the 19% CP diet was fed for exactly 7 or 21 d before switching to the 15% CP diet. In all experiments, Hubbard Standard pullets weighed significantly more than Hubbard Hi-Y pullets and had increased overall skeletal growth. When the pullets from both strains were restricted to only 380 g BW at 28 d, (Exp. 3) the longer period of protein intake significantly enhanced breast muscle weight but there were no significant strain differences. When BW at 28 d was increased to 480 g, (Exp. 2), dietary protein and strain differences were observed.