An analysis of the adverse events (AEs) reported following distribution of Merck & Co's quadrivalent human papillomavirus (qHPV) recombinant vaccine, Gardasil, since 2006, has indicated that AE rates were consistent with prelicensing data and expected background rates of other vaccines, with the exception of a higher proportion of reports of fainting and blood clots.
Gardasil is the world's first cervical cancer vaccine, which can also help to prevent vulvar and vaginal cancers and genital warts caused by HPV types 6, 11, 16 and 18. In June 2006, the FDA licensed Gardasil for females aged nine to 26 years to prevent infection with genital HPV. Shortly after that, the Advisory Committee on Immunization Practices recommended routine vaccination of females aged 11 to 12 years with three doses of qHPV and catch-up vaccination for females aged 13 to 26 years.
In the new study, published in the 19th August issue of JAMA (2009;302:750-757), the researchers analysed reports of AEs following qHPV immunisation received by the Vaccine Adverse Event Reporting System (VAERS) from 1st June 2006 until 31st December 2008. Additional analyses were performed for some AEs following immunisations (AEFIs) in prelicensure trials, those of unusual severity or those that had received public attention.
During the study period, VAERS received 12,424 reports of AEFIs following receipt of qHPV, an overall reporting rate of 53.9 reports per 100,000 vaccine doses distributed. Of the 8,247 reports that included onset interval, 4,393 (40 per cent) occurred on the day of vaccination. Among 9,396 reports (77 per cent) with dose information, 5,772 (61 per cent) followed the first dose, 2,380 (25 per cent) followed the second dose and 1,183 (13 per cent) followed the third dose of qHPV.
Among the 12,424 AEFI reports, 772 (6.2 per cent) were serious, including 32 reports of death. The reporting rates per 100,000 qHPV doses distributed were: 8.2 for syncope; 7.5 for local site reactions; 6.8 for dizziness; 5.0 for nausea; 4.1 for headache; 3.1 for hypersensitivity reactions; 2.6 for urticaria; 0.2 for venous thromboembolic events, autoimmune disorders and Guillain-Barré syndrome; and 0.1 for anaphylaxis and death. Analysis indicated a disproportional reporting of fainting and blood clot events.
The VAERS database that was the primary source for the study is one of the many mechanisms used to assess the safety of vaccines. Merck also monitors vaccine safety by conducting comprehensive analyses of AEs reported to the company and shares these analyses with the Centers for Disease Control and Prevention (CDC), the FDA, and regulatory and medical authorities around the world to support their efforts. After carefully reviewing all of the information available to Merck about reported AEs, including the findings in the discussed study, the company continues to be confident in the safety profile of Gardasil. While no vaccine or medicine is completely without risk, leading health organisations throughout the world, including the CDC and EMEA, have reviewed the available safety and efficacy information about Gardasil and continue to recommend its use.
Richard M Haupt, head of the Gardasil clinical programme commented: "we will continue our practice of effectively communicating the safety profile of Gardasil, it's a responsibility Merck takes very seriously...Parents should understand the extensive data supporting the safety profile of this vaccine, and we encourage them to look to CDC and FDA, and to the advice of their own physicians, to make an informed choice about something as important as a vaccine to help prevent cervical cancer".
Alice Rossiter Cancer Drug News Editor
Wednesday, August 26, 2009
Wednesday, August 12, 2009
Nanobees take the sting out of cancer
Researchers at Washington University School of Medicine in St Louis have harnessed the toxin in bee venom to kill tumour cells by attaching the major component of the venom to nano-sized spheres that they call nanobees. In mice, nanobees delivered the bee toxin, melittin, to tumours, while protecting other tissues from the toxin's destructive effects. The tumours were shown to stop growing or shrank.
Melittin is a small protein, or peptide, which is strongly attracted to cell membranes, where it can form pores that break up cells and kill them. Professor Samuel Wickline, a specialist in nanomedicine at Washington University who led the research, explained: "the nanobees fly in, land on the surface of cells and deposit their cargo of melittin, which rapidly merges with the target cells." The investigators have shown that the bee toxin is taken into the cells where it pokes holes in their internal structures.
As detailed in the 10th August online edition of the Journal of Clinical Investigation (10.1172/JCI38842), the scientists tested nanobees in two kinds of mice with cancerous tumours. One mouse breed was implanted with human breast cancer (BC) cells and the other with melanoma tumours. After four to five injections of the melittin-carrying nanoparticles over several days, growth of the BC tumours slowed by nearly 25 per cent, and the size of the melanoma tumours decreased by 88 per cent compared to untreated tumours.
The researchers indicated that the nanobees gathered in these solid tumours because they often have leaky blood vessels and tend to retain material. Scientists call this the "enhanced permeability and retention effect of tumours", and it explains how certain drugs concentrate in tumour tissue much more than they do in normal tissues. Further, the researchers developed a more specific method for ensuring that nanobees target tumours and not healthy tissue, by loading them with additional components. When they added a targeting agent that was attracted to growing blood vessels around tumours, the nanobees were guided to precancerous skin lesions that were rapidly increasing their blood supply. Injections of targeted nanobees reduced the extent of proliferation of precancerous skin cells in the mice by 80 per cent.
The flexibility of nanobees and other nanoparticles made by the group suggests that they could be readily adapted to fit medical situations as needed. The ability to attach imaging agents to nanoparticles means that they can give a visible indication of how much medication reaches tumours and how they respond. Potentially, it is thought that these could be formulated for a particular patient. Overall, the results suggest that nanobees could not only lessen the growth and size of established cancerous tumours, but also act at early stages to prevent cancer from developing.
Alice Rossiter - Cancer Drug News Editor
Melittin is a small protein, or peptide, which is strongly attracted to cell membranes, where it can form pores that break up cells and kill them. Professor Samuel Wickline, a specialist in nanomedicine at Washington University who led the research, explained: "the nanobees fly in, land on the surface of cells and deposit their cargo of melittin, which rapidly merges with the target cells." The investigators have shown that the bee toxin is taken into the cells where it pokes holes in their internal structures.
As detailed in the 10th August online edition of the Journal of Clinical Investigation (10.1172/JCI38842), the scientists tested nanobees in two kinds of mice with cancerous tumours. One mouse breed was implanted with human breast cancer (BC) cells and the other with melanoma tumours. After four to five injections of the melittin-carrying nanoparticles over several days, growth of the BC tumours slowed by nearly 25 per cent, and the size of the melanoma tumours decreased by 88 per cent compared to untreated tumours.
The researchers indicated that the nanobees gathered in these solid tumours because they often have leaky blood vessels and tend to retain material. Scientists call this the "enhanced permeability and retention effect of tumours", and it explains how certain drugs concentrate in tumour tissue much more than they do in normal tissues. Further, the researchers developed a more specific method for ensuring that nanobees target tumours and not healthy tissue, by loading them with additional components. When they added a targeting agent that was attracted to growing blood vessels around tumours, the nanobees were guided to precancerous skin lesions that were rapidly increasing their blood supply. Injections of targeted nanobees reduced the extent of proliferation of precancerous skin cells in the mice by 80 per cent.
The flexibility of nanobees and other nanoparticles made by the group suggests that they could be readily adapted to fit medical situations as needed. The ability to attach imaging agents to nanoparticles means that they can give a visible indication of how much medication reaches tumours and how they respond. Potentially, it is thought that these could be formulated for a particular patient. Overall, the results suggest that nanobees could not only lessen the growth and size of established cancerous tumours, but also act at early stages to prevent cancer from developing.
Alice Rossiter - Cancer Drug News Editor
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