Introduction: The substantial pandemic (A/H1N1v) influenza disease burden in children highlights the need for effective vaccination. We report the results of modern cell culture technology, lower doses of antigen, and different doses of MF59® adjuvant (Novartis Vaccines, Marburg, Germany), on the immunogenicity and safety profile in a healthy Japanese pediatric population. Methods: A total of 123 children from 6 months to 19 years of age were randomly assigned in a 1:1 ratio to receive, at 21-day intervals, two doses of either 3.75 μg antigen with 50% of the standard MF59 dose (group A) or 7.5 μg antigen and 100% standard MF59 dose (group B). Antibody levels were measured by hemagglutinin inhibition (HI) and microneutralization assays on day 1 and on days 22 and 43 (3 weeks after the first and second vaccinations, respectively). Solicited adverse events were reported for 7 days after each injection and spontaneous events were reported throughout the study period. Results: At 3 weeks after the first vaccination, seroprotective HI antibodies (titers ≥40) were observed in 56% and 78% of subjects from groups A and B, respectively; 100% in both groups exhibited HI titers ≥40 after the second dose. The reactogenicity profile was acceptable, with local and systemic reactions described as mainly mild to moderate in severity. Five serious adverse events were reported, but none related to the study vaccine. Conclusion: One dose of cell culture-derived A/H1N1v vaccine containing 7.5 μ g antigen with the full MF59 adjuvant dose was immunogenic and well tolerated in healthy Japanese children, meeting all three European Union Committee for Medicinal Products for Human Use (EU CHMP) licensure criteria. Two doses of 3.75 μg antigen with 50% of the standard MF59 dose fulfilled these licensure criteria.

Background: Irinotecan and S-1, an oral fluoropyrimidine composed of tegafur, gimeracil, and oteracil potassium, have demonstrated antitumor activity against advanced gastric cancer. We performed a phase 1/2 study to determine the recommended dose, antitumor activity, and safety of a combination of S-1 and irinotecan in patients with advanced gastric cancer. Methods: Patients with previously untreated advanced gastric cancer were enrolled. Patients received irinotecan intravenously on days 1 and 15 plus oral S-1 twice daily on days 1-14 of a 28-day cycle. In the phase 1 part, the dose of irinotecan was escalated from 100 mg/m2 to 125 mg/m2 and then to 150 mg/m2. Results: A total of 24 patients were enrolled. Overall, the median number of treatment cycles per patient was 5.9, and 92% of the patients completed at least two cycles. The overall response rate was 54.2% (13 of 24). The response rates in differentiated and undifferentiated cancer were 56.3% (nine of 16) and 50.0% (four of eight), respectively. Median survival time was 581 days. The maximum tolerated dose of irinotecan was not reached at the highest level. However, grade 4 neutropenia occurred at 125 mg/m2. We concluded that the recommended dose of irinotecan for the present regimen was 125 mg/m2. Conclusion: Treatment with S-1+irinotecan is considered effective in patients with advanced gastric cancer who have not previously received chemotherapy. A combination of irinotecan and S-1 was well tolerated in patients with advanced gastric cancer and could be given on an outpatient basis.

Introduction: Flavocoxid, a botanical, anti-inflammatory agent, nonspecifically inhibits the peroxidase activity of cyclooxygenase (COX-1 and COX-2) enzymes and 5-lipooxygenase (5-LOX). Due to the concomitant use of aspirin or warfarin in many osteoarthritis (OA) patients with increased cardiovascular risk, we felt it necessary to assess the anticoagulation properties of flavocoxid. Methods: Three different studies were used: 1) a mouse model to assess effects on bleeding times when combined with aspirin; 2) the effect on platelet function as evaluated by platelet aggregation and bleed times in healthy human subjects; and 3) the effect on international normalized ratio in previously warfarinized patients with OA. Results: Flavocoxid at a human equivalent dose (HED) of 569 mg (within the standard human dosing range of 500 mg) produced no significant increases in bleeding time in mice. There was also no inhibition or synergistic increase in bleed times when flavocoxid was combined with aspirin (370 mg HED). Flavocoxid did not significantly inhibit thromboxane production or platelet aggregation, and did not increase bleeding times in healthy volunteers. Finally, flavocoxid did not inhibit or potentiate the anticoagulant effect of warfarin. Conclusion: These results suggest that flavocoxid does not affect the primary or extrinsic pathways of secondary hemostasis and, by not inhibiting the anticoagulation effects of aspirin, may have utility in cardiovascular patients with OA.