Welfare of domestic birds and rabbits transported in containers.

This opinion, produced upon a request from the European Commission, focuses on transport of domestic birds and rabbits in containers (e.g. any crate, box, receptacle or other rigid structure used for the transport of animals, but not the means of transport itself). It describes and assesses current transport practices in the EU, based on data from literature, Member States and expert opinion. The species and categories of domestic birds assessed were mainly chickens for meat (broilers), end-of-lay hens and day-old chicks. They included to a lesser extent pullets, turkeys, ducks, geese, quails and game birds, due to limited scientific evidence. The opinion focuses on road transport to slaughterhouses or to production sites. For day-old chicks, air transport is also addressed. The relevant stages of transport considered are preparation, loading, journey, arrival and uncrating. Welfare consequences associated with current transport practices were identified for each stage. For loading and uncrating, the highly relevant welfare consequences identified are handling stress, injuries, restriction of movement and sensory overstimulation. For the journey and arrival, injuries, restriction of movement, sensory overstimulation, motion stress, heat stress, cold stress, prolonged hunger and prolonged thirst are identified as highly relevant. For each welfare consequence, animal-based measures (ABMs) and hazards were identified and assessed, and both preventive and corrective or mitigative measures proposed. Recommendations on quantitative criteria to prevent or mitigate welfare consequences are provided for microclimatic conditions, space allowances and journey times for all categories of animals, where scientific evidence and expert opinion support such outcomes.

Monoclonal antibody-based ELISA for detection of antibodies against H5 avian influenza viruses.

Diagnostic and containment measures are essential for the management of avian influenza. In this study, a monoclonal antibody (MAb)-based competitive ELISA for detecting antibodies against H5 avian influenza viruses was developed and validated. Twenty-five anti-H5 MAbs were characterised using competitive, indirect and sandwich ELISAs, immunofluorescence, Western blotting and virus neutralisation and haemagglutination inhibition assays. One MAb (5D8) with wide intra-subtype cross-reactivity was selected and characterised using escape mutant selection. Epitope analysis showed that this MAb recognises a conformational epitope comprising amino acid residues in positions 170, 235 and 240 located in the receptor binding domain. The diagnostic performance of the test was evaluated by ROC analysis using a panel of 950 known sera collected from different avian species, including chickens, turkeys, ducks, pheasants, wild Anseriformes and ostriches. The competitive ELISA had excellent diagnostic performance and discriminatory power with high Se and Sp values (Se: 99.6-95% CI 98.0-100; Sp: 99.4-95% CI 98.5-99.8). In addition to its excellent diagnostic performance, properties of the competitive ELISA, such as high feasibility of testing sera without pre-treatment and potential for automation and instrument-mediated detection, make it ideal for screening samples, confirming positive HI assay results or analysing samples that are difficult to test using the HI assay.

A phase I/II study of LY900003, an antisense inhibitor of protein kinase C-alpha, in combination with cisplatin and gemcitabine in patients with advanced non-small cell lung cancer.

PURPOSE: Protein kinase C-alpha has been implicated in malignant transformation and proliferation. Based on in vivo superadditive interaction between the protein kinase C-alpha antisense oligonucleotide LY900003 (Affinitak, ISIS 3521) and cisplatin, we designed this phase I/II trial of LY900003 with cisplatin/gemcitabine. EXPERIMENTAL DESIGN: The safety of the combination, as well as potential pharmacokinetic interactions, was evaluated in the phase I portion of the trial. The phase II portion evaluated the antitumor activity of the combination in previously untreated patients with stage IIIB/IV non-small-cell lung cancer (NSCLC). RESULTS: Seven patients received 18 cycles of the combination during the phase I portion. Dose-limiting toxicity was only observed in one of six evaluable patients (grade 3 fatigue). However, due to a relatively high frequency of thrombocytopenia, cisplatin 80 (mg/m2) and gemcitabine (1,000 mg/m2) were recommended for the phase II portion. Antitumor activity was observed in two patients (one with NSCLC and one with pancreatic carcinoma), and prolonged stabilization was observed in two others. No pharmacokinetic interactions occurred. In the phase II portion, 55 NSCLC patients received the combination at two gemcitabine doses [1,000 mg/m2, n=44 (original cohort); 1,250 mg/m2, n=11 (expanded cohort)]. Fourteen of 39 evaluable patients in the original cohort had a response rate (1 complete response and 13 partial responses; response, 36%), whereas 2 of 9 evaluable patients in the expanded cohort experienced partial response (combined response rate, 33%). The median time to treatment failure was 3.9 months, whereas the median time response to progression for the 48 patients with evaluable response was 4.4 months (confidence interval, 3.5-5.5 months). Intent to treat median survival time was 8.9 months. Forty-eight percent of the patients experienced catheter-related events. CONCLUSIONS: LY900003 can be administered safely in combination with cisplatin and gemcitabine and is associated with antitumor activity in patients with advanced NSCLC. Better characterization of subsets of patients most likely to benefit from this combination therapy is needed.

Preoperative chemotherapy and radiation for advanced esophageal carcinoma: comparison between once a day radiation and hyperfractionation, a single-institution experience.

The purpose of this study was to determine the toxicity and efficacy of single daily fractionation as compared with twice-a-day radiation therapy in combination with chemotherapy for preoperative locally advanced thoracic esophageal carcinoma. A retrospective survey was done of 42 patients undergoing concurrent chemotherapy and radiation for preoperative locally advanced thoracic esophageal carcinoma. Twenty-five patients had 5-fluorouracil ([5-FU]), 1,000 mg/m2/d by continuous infusion, days 1-5, and days 22-26), cisplatin (100 mg/m2 intravenously, days 2 and 22), and radiation to a total dose of 4,500 to 5,040 cGy in 180 cGy/fraction every day. Seventeen patients received 5-FU (300 mg/m2/d by continuous infusion, days 1 and 21), cisplatin (20 mg/m2/d for 1 hour, days 1-5 and days 17-20), vinblastine (1 mg/m2 intravenously, days 1-5 and days 17-21) and accelerated hyperfractionated radiation 150 cGy twice a day to a total dose of 4,500 cGy. Response rate, survival, local regional failure rates, and treatment toxicity of the two groups were compared. Surgery was aborted in one patient and another patient refused surgery in the single daily-fractionation group. All patients underwent surgery in the twice-daily group. Complete response (CR) was noted in 12 patients (52%) in the single daily-fractionation group as compared with 9 patients (52%) in the twice-daily group. The median and 3-year survival were 20 months and 35%, respectively, in the single daily-fractionation group. Corresponding figures were 18 months and 32%, respectively, in the twice-daily group. For the 2 groups combined, a statistically significant improvement in survival was observed among blacks who achieved a CR (31 months) as compared with the ones with residual disease (13.5 months). Local and regional failures were 28% and 17%, respectively, for the single daily-fractionation and twice-daily groups. Distant metastases remained significant in both groups and were 36% (single daily-fractionation) and 41% (twice-daily), respectively. Grades III to IV esophagitis and hematologic toxicity developed in 36% and 64% of patients of the single daily-fractionation and twice-daily groups, respectively. The incidence of late complications was 16% (single daily-fractionation) and 11.7% (twice-daily). Preoperative chemotherapy and radiation is effective to achieve a high pathologic CR. Both radiation therapy fractionation schedules are comparable in efficacy and toxicity. Further investigations should be done to assess whether ethnicity may play a role in the prognosis of esophageal carcinoma.

Efficacy of combined radiation, paclitaxel and carboplatin for locally advanced non-small cell lung carcinoma.

Locally advanced non-small cell lung carcinoma (NSCLC) has a poor prognosis when treated with conventional chemotherapy and radiation. New chemotherapy agents like paclitaxel may increase the sensitivity of tumors cells to radiation and potentially improve the outcome. The optimal combination of taxane-based chemotherapy agents and radiation is still unclear. We investigated the feasibility of induction chemotherapy followed by concurrent near systemic dose of chemotherapy with radiation. A prospective survey of 29 previously untreated patients with unresectable stage III (15 IIIA, 14 IIIB) NSCLC treated with paclitaxel and carboplatin in combination with radiation was reviewed. The patients received 2 cycles of paclitaxel 225 mg/m2 intravenously (i.v.) over 3 hours, days 1, 22; carboplatin at area under the curve (AUC) 6 based on Calvert formula days 1, 22 following completion of the paclitaxel infusion. Following induction chemotherapy, radiation therapy started on day 43 until completion to a tumor dose of at least 5960 cGy. Cycles 3 and 4 of chemotherapy were begun on days 43 and 63, respectively, and consisted of paclitaxel 175 mg/m2 i.v. over 3 hours, and carboplatin at AUC 6 following paclitaxel infusion. The response rate, acute toxicity, long-term complications, pattern of failure and survival were evaluated and compared to previous studies in the literature. Two patients were lost to follow-up. The response rate to induction carboplatin/paclitaxel was 52%. An overall response rate (complete and partial responders) of 85% was obtained following chemotherapy and radiation. Grade 3-4 acute side-effects were recorded in 9 patients (31%) and consisted of esophagitis (8 patients) and anemia (1 patient). One patient died from cachexia 3 months following treatment (3.7%). The median survival and 3-year survival were 15 months and 30%, respectively, for the remaining 27 patients at a median follow-up of 11 months. There was no difference in survival between stages IIIA and IIIB at 2 years (IIIA: 22%, IIIB: 31%). Local or regional recurrences and distant metastases developed in 9 patients (33%) and 13 patients (46%), respectively. The combination of paclitaxel, carboplatin and radiation for locally advanced non-small cell carcinoma is feasible with acceptable toxicity. The response rate compares favorably with previously reported studies. The decrease of tumor volume following induction chemotherapy allows sparing of the lungs from the toxicity of radiation. However, grades 3-4 esophagitis remain significant. The addition of amifostine may be beneficial in this setting.