Jury still out on clinical exams for breast cancer screening

Medical Tribune October 2009 P12

David Brill

Controversy looks set to continue over the benefits of clinical breast examination (CBE) for cancer screening, following the publication of a large population-based study which could raise as many questions as answers.

Results from the Ontario Breast Screening Program show that adding CBE to mammography improves cancer detection rates, but considerably increases the number of false-positive results.

For every 10,000 women screened, the addition of CBE would detect four more cancers but expose 219 women to unnecessary further testing – along with its extra risks, costs and anxiety.

This risk-benefit ratio must be weighed up carefully, and women should be fully informed before consenting to CBE, wrote the researchers, led by Dr. Anna Chiarelli of Cancer Care Ontario, Toronto Canada. [J Natl Cancer Inst 2009 Aug 31; Epub ahead of print]

They screened 290,230 women aged 50 to 69 between 2002 and 2003, and followed them up for 12 months. Of these women, 232,515 received mammography plus CBE at 68 centers (nine regional and 59 affiliated), whereas 57,715 received mammography alone at 34 affiliated centers.

US experts called it “a steep price” for adding CBE to mammography but reserved judgment on how the findings should influence practice, concluding in an editorial that “more answers are needed on the role of CBE in breast cancer screening before definitive recommendations for or against its use can be made.”

“While we wait for those answers, the data presented by Chiarelli et al. suggest that CBE must be done well if it is to be done at all, with the acknowledgment that overall referrals and false-positive results will increase,” wrote Drs. Mary Barton and Joann Elmore, of the Agency for Healthcare Research and Quality, Rockville, and the University of Washington School of Medicine, Seattle, respectively. [J Natl Cancer Inst 2009 Aug 31; Epub ahead of print]

Barton and Elmore also called for the creation of universal standards for CBE, noting that inconsistency in the duration of examinations and the search pattern used can affect the accuracy of the test. They note that the highest-volume centers in the Ontario study also had the highest sensitivities and lowest false-positive rates – an observation which supports their case for standardization.

CBE has been advocated in some quarters since it can detect cancers which are missed by mammography – the gold standard for breast cancer screening. It has yet to be demonstrated conclusively, however, that addition of CBE to screening actually reduces mortality.

The practice is common in the US: one report found that 18 percent of screening centers surveyed performed CBE routinely alongside mammography, while another study found that 65 percent of women reported having CBE in the preceding 2 years. [Open Clin Cancer J 2008;2:32-43; AJR Am J Roentgenol 2005;184:433-8]

Breast cancer was traditionally less common in Asia than the West but rates are rising rapidly. In Singapore, the only Asian country with a national breast cancer screening program, it is now the number one cancer among women. The incidence rose 2.5-fold between 1968 and 2002, according to data from the national cancer registry.

First-line screening in the BreastScreen Singapore program is with mammography alone. CBE is included among possible follow-up tests, along with ultrasound, repeat mammography and biopsy.

Breast cancer has also become the leading cancer among women in Hong Kong – responsible for 21 percent of cancer cases in 2002. A self-referral, opportunistic mammography screening program at the Tung Wah Group of hospitals was shown to improve early detection and prognosis after 46,637 mammograms, with comparable results to Western programs. Screening was well received by the community, and the model has been proposed as a basis for a national program. [Hong Kong Med J 2007;13:106-13c]

Surveys in both Singapore and Hong Kong have shown, however, that public knowledge about breast cancer and screening is low, and myths and misconceptions are common. Only 57 percent of Singaporean women aged 40 and above had gone for a screening mammogram, while 58 percent of Hong Kong women had never even heard of mammographic screening. [Singapore Med J 2009;50:132-8; Breast J 2005;11:52-6]

Aspirin trial seeks to tackle colorectal cancer in Asia

Medical Tribune September 2009 P8
David Brill

A major new trial is set to launch in Asia to establish whether aspirin can prevent recurrence of colorectal cancer.

The ASCOLT study will involve over 2,000 patients from centers across Southeast Asia, China and India, and will be led jointly by the National Cancer Centre Singapore (NCCS) and the University of Oxford, UK.

Patients will be randomized to aspirin (200mg/day) or placebo for 3 years, following surgery and adjuvant chemotherapy for high-risk stage II and III colorectal cancer. The primary endpoint will be disease-free survival over 5 years of follow-up.

A growing body of evidence suggests that aspirin is effective for primary prevention of colorectal cancer, but ASCOLT is thought to be the first prospective clinical study to investigate the drug in the adjuvant setting after chemotherapy.

If positive, the results could have a huge impact on the treatment of colorectal cancer in Asia and worldwide, according to Dr. Toh Han Chong, head of the department of medical oncology at NCCS and one of the ASCOLT lead investigators.

“It’s incredible how many people you could save from relapse with the addition of aspirin if this study is positive. If you go to a village in India you can’t really give costly [monoclonal antibodies], so there is compelling power of social responsibility here,” he told Medical Tribune.

“We have undervalued the power of simple drugs. It’s time to redress the balance – change the paradigm and go cheap.”

Recruitment for ASCOLT is already underway, with centers confirmed in Singapore, Hong Kong, Jakarta and several cities in India.

More study centers are still needed in order to reach the target of 2,000 patients however said Toh, who extended the invite to all Asian delegates at the recent ‘Best of ASCO’ conference in Singapore.

“It’s a drug trial that cannot be done in the West. Many people over the age of 50 in the US are popping aspirin over the counter for heart conditions or stroke prevention,” he said. “Fewer people are on aspirin in Asia. That’s why it’s a perfect study to do here.”

Colorectal cancer is the second leading cause of cancer death in North America, Europe and Australasia according to a 2007 global report from the American Cancer Society. In Southeast Asia, it is the third biggest killer (behind liver and lung cancer) – responsible for 7.9 percent of cancer deaths.

In Singapore, colorectal cancer is the leading cancer among men and the second most common among women, data from the national cancer registry show.

A recent study found that regular use of aspirin after a diagnosis of colorectal cancer was associated with lower overall mortality (hazard ratio [HR] 0.79; 95% CI 0.53 – 0.95) and cancer-specific mortality (HR 0.71; 0.53 – 0.95), after a median of 11.8 years of follow-up. [JAMA 2009;302(6):649-58]

A 2007 paper, meanwhile, reported that taking 300 mg/day or more of aspirin for 5 years was effective for primary prevention of colorectal cancer, according to pooled data from two large randomized trials (HR 0.74; 95% CI 0.56 – 0.97; P=0.02). [Lancet 2007;369(9573):1603-13] Earlier trials have also shown that aspirin can prevent colorectal adenomas – the precursors to cancer – both in patients with, and without, a prior history of cancer. [N Engl J Med 2003;348(10):883-90; N Engl J Med 2003;348(10):891-9]

“Why should oncologists do an aspirin trial? Because the epidemiological data is strong, the data on polyp reduction is very convincing, the retrospective observational studies are very compelling and remarkable in terms of hazard ratios, and the data preclinically is scientifically robust,” added Toh.

ASCO award set to boost Asian cancer research

Medical Tribune September 2009 P8
David Brill

A Singapore oncologist has become the first Singaporean, and one of the first Asia-based recipients, to pick up a prestigious research award from the American Society of Clinical Oncology (ASCO).

Dr. Daniel Tan of the National Cancer Centre Singapore (NCCS) will receive a US$50,000 grant as part of the Young Investigator Award, bestowed by the ASCO cancer foundation.

The money will help fund his research on the molecular mechanisms of tyrosine kinase inhibitors (TKIs) in nasopharyngeal cancer. The work aims to understand why some patients respond better to targeted therapies than others – so as to improve patient selection and avoid unnecessary exposure to ineffective treatment and side effects.

“One of the challenges with any of these new-generation drugs is to find out how we can use them better – to get the right drug to the right patient. Understanding the reasons for response and resistance can also allow us to develop much more effective treatment strategies that hopefully translate to improved survival,” said Tan, who will work alongside his mentor Professor Teh Bin Tean, director of the NCCS-VARI laboratory – a joint project with the Michigan-based Van Andel Research Institute.

Tan’s ASCO proposal was borne out of clinical observations from a phase II trial of pazopanib, which saw a subset of nasopharyngeal cancer patients respond better to therapy than others. This trial is currently ongoing under principal investigator Dr. Darren Lim, a senior consultant at NCCS specializing in thoracic and head and neck cancers.

The goal now is to understand which proteins are targeted by the drug, and how this differs between patients and tumor types. Tan’s work will be done largely in a series of co-culture experiments and mouse xenograft models – allowing detailed analysis of how the drug affects each cellular compartment within a tumor.

Tan is also aiming to secure more local funding for his research, and hopes in the long term to help establish a comprehensive drug development program, which would also provide patients with access to novel therapeutic agents.

He added that he was pleased to receive the award, and is especially encouraged that the proposal was deemed to have sufficient scientific merit for further study.

“It is heartening to know that one’s ideas are being taken seriously by a highly regarded scientific body. Furthermore, the award is rarely given out to institutions outside of America, so it’s a nice endorsement of the research infrastructure at NCCS,” he said.

Cetuximab offers hope for Asian lung cancer patients

Medical Tribune September 2009 P8
David Brill

A novel lung cancer therapy could be of particular benefit to Asian patients, results of a recent trial suggest.

The international FLEX* study reported that adding the monoclonal antibody cetuximab to chemotherapy prolonged survival of advanced lung cancer patients from 10.1 months to 11.3 months.

Further analysis revealed, however, that Asians treated with the drug survived for a median of 19.5 months, whereas non-Asians survived only 9.6 months.

The randomized trial involved 1,125 patients – 121 of whom were from Asian centers (predominantly in Hong Kong, Taiwan, Singapore and South Korea). [Lancet 2009;373(9674):1525-31]

There are several possible explanations for the ethnic discrepancy but also questions that remain unanswered, according to Professor Kenneth O’Byrne, one of the FLEX investigators, who spoke to Medical Tribune during the recent ‘Best of ASCO’ conference in Singapore.

Asian lung cancer patients are more likely to be women, non-smokers and have adenocarcinomas than non-Asian patients – all groups which tend to survive longer, he said. Moreover, epidermal growth factor receptor (EGFR) mutations are more common among Asians – a characteristic which not only improves prognosis in itself, but also makes patients eligible for first-line EGFR tyrosine kinase inhibitors which can further improve outcomes.

“So there is a combination of reasons as to why but it’s not just that – there may be some intrinsic sensitivity to treatment here that’s not present in the West,” said O’Byrne, adding that further study is needed to better understand these biological similarities and differences.

Cetuximab is presently licensed for use only in colorectal and head and neck cancers. An application for lung cancer licensing was recently rejected by the European Medicines Agency (EMEA), but is currently under appeal from the manufacturer, Merck Serono.

The verdict has also come as a surprise to many experts in the field and will face “a strong challenge,” said O’Byrne, a consultant medical oncologist at St. James’s Hospital and a clinical professor at Trinity College, Dublin, Ireland. The FLEX trial was published before the EMEA decision, with investigators concluding that cetuximab can be considered as standard first-line therapy for all patients with advanced non-small cell lung cancer (NSCLC).

“Cetuximab is the first drug to show a survival benefit in all histological types: adenocarcinoma, squamous carcinoma – across the board. Secondly, the toxicities are all very predictable – we know how to manage them and they’re straightforward. Thirdly, not only was the FLEX trial positive but when you take in all the other trials together … as a collective they show a positive result,” said O’Byrne. He added that US National Comprehensive Cancer Network guidelines already recommend that the drug be considered for lung cancer patients, and that many oncologists in Europe have begun off-label usage.

O’Byrne acknowledged that cetuximab therapy would be costly, but noted that around half of patients display a strong predictive marker in the form of a skin rash, which develops after one round of chemotherapy. These patients tend to survive for around an extra 5 months, which may justify the cost, he said. More work is needed to confirm whether cetuximab offers any benefit for those who do not develop a rash, but it appears likely that therapy could be discontinued after one cycle in these patients, he said.

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*FLEX: First-Line Erbitux in Lung Cancer

Bacteria eradication holds hope for stomach cancer prevention

Medical Tribune September 2009 P14

David Brill

A new study has renewed hopes for reducing the incidence of gastric cancer – a leading cause of death worldwide and a particular burden for Asia.

The link between Helicobacter pylori infection and gastric cancer is well known, but Italian researchers now provide some of the strongest evidence yet that eradicating the bacteria can actually reduce cancer risk.

In a meta-analysis of data from 6,695 participants, they report that H. pylori eradication reduced the relative risk of gastric cancer to 0.65 (95 percent CI 0.43 – 0.98) over up to 10 years of follow-up. [Ann Intern Med 2009;151:121-8]

The findings lend support to a recent Asia-Pacific consensus statement calling for H. pylori screening and eradication in high-risk populations.

Japan and China have the world’s highest rates of gastric cancer, with age-standardized incidences of 62.1 and 41.4, respectively, per 100,000 males and 26.1 and 19.2 per 100,000 females. [CA Cancer J Clin 2005;55:74-108]

Dr. Lorenzo Fuccio, lead author of the meta-analysis, stressed that the cancer risk reduction with H. pylori eradication was only marginally significant, but could prove vital in countries such as these.

“Even a small reduction in risk and incidence achieved with H. pylori treatment will probably give a huge advantage in terms of social health, especially in high-risk areas,” said Fuccio, of the department of internal medicine and gastroenterology at the University of Bologna, Italy.

“Furthermore, H. pylori eradication provides several other benefits: it reduces the risk of peptic ulcer development, it can resolve dyspeptic symptoms and it can resolve gastritis. Once H. pylori is detected, especially in high-risk areas, eradication is always advisable.”

Asia-Pacific experts released their consensus statement on gastric cancer prevention last year, concluding that “there is a definite causal link between H. pylori infection and gastric cancer, and it has come time to try and intervene to prevent this cancer at the population level.” [J Gastroenterol Hepatol 2008;23:351-65]

Lead author Professor Fock Kwong Ming said that H. pylori screening and treatment should be a complement to, not a replacement for, existing cancer surveillance strategies in high-risk countries.

Research is still ongoing to establish exactly who to screen in intermediate-risk countries such as Singapore and Malaysia, said Fock, a senior consultant gastroenterologist at Changi General Hospital (CGH), Singapore. The highest-risk group in Singapore appears to be Chinese males aged 45 to 50, he said.

Previous work showed that gastric cancer risk correlated with H. pylori infection in Chinese and Malay individuals but not Indians. Gastric cancer rates are known to be lower in the latter two groups. [J Gastroenterol Hepatol 2005 Oct;20(10):1603-9]

Two studies are currently underway in Singapore to identify risk factors for gastric cancer development.

The first – a 5-year, S$25 million project conducted across several institutions in the Singapore Gastric Cancer Consortium – will correlate endoscopy and biopsy findings to gastric cancer outcomes, with a view to understanding how cancer develops and improving early detection rates. The second study takes place at CGH, and involves narrow-band endoscopy – a more specialized technique which may be better able to detect precancerous lesions.

Fuccio noted that randomized, multicenter trials are needed to fully understand the impact of H. pylori eradication on cancer prevention, but that such studies would present considerable ethical, logistical and financial challenges. Achieving statistical power would require thousands of participants and decades of follow-up, he said.

He added that gastric cancer results from a complex combination of genetic and environmental factors, and that eradicating H. pylori does not completely abolish risk.

H. pylori eradication is typically achieved using two antibiotics combined with a proton-pump inhibitor.

Hong Kong symposium: Facing up to the diabetes epidemic

Medical Tribune July 2009 P10
David Brill

The global diabetes epidemic has transcended medical specialties and become a priority for all healthcare professionals, say the organizers of this year’s Hong Kong Diabetes and Cardiovascular Risk Factors – East Meets West (EmW) symposium.

The meeting, to be held in September, will bring attendees up to speed on the latest research into the twin burdens of diabetes and cardiovascular disease (CVD).

With topics ranging from lifestyle interventions and nutrition to the management of diabetes in pregnancy, the symposium promises to deliver a host of practical insights for day-to-day patient care. Leading cardiologists will review strategies for assessing cardiovascular status in people with diabetes, while other sessions will address the crucial importance of good glycemic control, particularly in light of major recent studies such as ACCORD*, ADVANCE** and VADT***.

Other highlights include cutting-edge sessions on the pathogenesis of type 2 diabetes, including pancreatic beta-cell pathology, the developmental-origins hypothesis of diabetes and the role of lipid metabolism in insulin resistance.

“The rate of diabetes is now rampant in Asia, especially in young to middle-aged people. In some countries, the prevalence can be as high as 10 percent,” said Dr. Gary Ko, chairman of the organizing committee for the EmW symposium, now entering its eleventh year.

“The economic burden of diabetes to governments, and the health impact to individuals, cannot be overemphasized. Diabetes can be linked to all systems and specialties. We believe that a good and up-to-date understanding of diabetes is essential for all practicing doctors, be they family physicians, specialists or from other fields,” he said.

“We hope to arouse the attention of our clinicians, particularly those working in Asia, to the increasing epidemic of diabetes, its devastating morbidity and mortality, and what needs to be done to minimize the impact of diabetes and CVD on society.”

Managing weight and diet in type 2 diabetics is just one of the many challenging areas which will be addressed in depth at the EmW symposium, said Professor Ronald Ma, chairman of the EmW scientific committee. He highlighted a presentation by world-renowned endocrinologist Professor Harold Lebovitz, who will introduce a new gastrointestinal ‘pacemaker’ known as Tantalus, which can regulate appetite and help patients to lose weight. Leading Hong Kong nutritionist Ms. Lorena Cheung will offer a different angle – providing insights on how to advise patients on glycemic index and glycemic load.

US obesity expert Professor John Foreyt will also share his knowledge and experience as an investigator on the Look-AHEAD (Action for Health in Diabetes) trial – a successful lifestyle intervention study which helped overweight diabetics to lose an average of 8.6 percent of their weight, improve fitness, reduce medications and lower HbA1C by 0.7 percent, after just one year. [Diabetes Care 2007 Jun;30(6):1374-83]

The ACCORD, ADVANCE and VADT trials have shown the critical need to balance the benefits of blood glucose lowering against potential drug-related side effects, notably weight gain and hypoglycemia. In this session, Professor Brian Frier, of the University of Edinburgh, UK, will give an overview of hypoglycemia: its impact on cardiovascular events and the underlying mechanisms.

Hong Kong expert Professor Terrence Lao, meanwhile, will provide an Asian perspective on the ever-growing problem of gestational diabetes, while Professor Edwin Lee will probe the link between anti-psychotic medications and metabolic disorders. Finally, world expert Professor Edward Fisher will share his wisdom on the rationale and evidence for peer support in the management of diabetes.

Over 600 attendees from all over the world are expected at the EmW symposium, which will take place at the Hong Kong Convention and Exhibition Centre from 30 September to 1 October 2009.

The event is jointly organized by the Hong Kong Institute of Diabetes and Obesity at the Chinese University of Hong Kong, CMPMedica Pacific Limited, the Hong Kong Atherosclerosis Society, the Hong Kong Association for the Study of Obesity and the Hong Kong Foundation for Research and Development in Diabetes, with support from the Hong Kong Dietitians Association.

For more information, see: http://www.eastmeetswest.org.hk/

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*ACCORD: Action to Control Cardiovascular Risk in Diabetes
**ADVANCE: Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation
***VADT: Veterans Affairs Diabetes Trial

Voglibose prevents diabetes in high-risk Asians

Medical Tribune July 2009 SFII
David Brill

Alpha-glucosidase inhibitors could play an important role in preventing, as well as treating, the growing epidemic of type 2 diabetes in Asia.

A recent trial found that adding voglibose to diet and exercise counseling almost halved the risk of developing diabetes in Japanese patients with impaired glucose tolerance (IGT).

The study extends similar findings from Western populations, where acarbose has been shown to reduce the progression from IGT to diabetes – notably in the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) trial. [Lancet 2002;359(9323):2072-7] Equivalent studies in Asian populations, however, were previously lacking.

The researchers, led by Professor Ryuzo Kawamori, Juntendo University School of Medicine, Tokyo, randomized subjects to placebo or voglibose (0.2 mg three times a day). The trial was terminated early, following an interim analysis. [Lancet 2009;373(9675):1607-14]

At a mean of 48 weeks of treatment, 50 of 897 patients taking voglibose had developed diabetes, compared to 106 of 881 who took placebo (hazard ratio 0.595, 95 percent CI 0.43 – 0.82; P=0.0014). More people achieved normoglycemia in the voglibose group: 559 of 897, versus 454 of 881 in the placebo group (P<0.0001).

Singapore diabetes expert Dr. Kevin Tan said that alpha-glucosidase inhibitors offer a good option in cases which need more aggressive intervention than lifestyle therapies alone.

“The results of this study mirror those of acarbose in STOP-NIDDM and demonstrate the efficacy of this group of alpha-glucosidase inhibitors in preventing type 2 diabetes – now in an Asian population as well,” said Tan, vice president of the Diabetic Society of Singapore and a private practitioner at Mount Elizabeth Medical Centre.

“Lifestyle interventions remain central as they are simple and available to all and, moreover, their effects are sustainable. However, lifestyle interventions are notoriously difficult to maintain at the same intensity over time and therefore safe and effective medications to complement them are needed as well. Alpha-glucosidase inhibitors are amongst the safest of compounds as there is minimal absorption into the body and no interference with the metabolism of other drugs,” he said.

The epidemic of type 2 of diabetes continues to boom in Asia, with total numbers predicted to increase from some 114 million patients in 2007 to 180 million in 2025. The prevalence of IGT is expected to rise from 157 million to 213. [JAMA 2009 May 27;301(20):2129-40]

The worst-affected countries appear to be those undergoing significant economic and dietary changes: the overall prevalence in China, for example, rose from 1 percent in 1980 to 5.5 percent in 2001. For affluent urban areas such as Hong Kong and Taiwan, the figure is as high as 10 percent. [Diabetes Res Clin Pract 2006 Aug;73(2):126-34]

Adverse events in the Japanese study were more common with voglibose than placebo (P<0.0001) – mostly comprising gastrointestinal symptoms such as flatulence, abdominal distention and diarrhea. There were also six serious advents in the voglibose group, consisting of colonic polyp, cholecystitis, inguinal hernia, liver dysfunction, rectal neoplasm and subarachnoid hemorrhage. Two placebo patients experienced serious events – one cerebral infarction and one case of cholecystitis.

Alpha-glucosidase inhibitors could feasibly be given in combination with metformin, which has also shown good results in diabetes prevention studies, wrote Dr. André Scheen of the University of Liège, Belgium, in an accompanying commentary. This dual approach, using acarbose, is currently being trialed in Canada. [Lancet 2009 May 9;373(9675):1579-80; Diabetes Obes Metab 2006;8(5):531-7]

Gene variants point to East Asian health risks

Medical Tribune June 2009 P3
David Brill

Korean scientists have identified East Asian-specific gene variants which play a role in obesity, blood pressure, bone density and pulse rate.

The group, led by the National Institute of Health, Seoul, conducted the first large-scale genome-wide association study of an East Asian population. They analyzed 8,842 samples from Korean population-based cohorts.

Besides identifying novel East Asian gene variants, they also found that many genetic markers are shared with Europeans, including several which play a role in height, body mass index, type 2 diabetes, obesity, heart disease and osteoporosis. [Nat Genet 2009 May;41(5):527-34]

Alcohol ‘flush’ signals cancer risk in Asians

Medical Tribune June 2009 P4

David Brill

East Asians who ‘flush’ when drinking alcohol could be at increased risk of esophageal cancer if they do not drink responsibly, a recent study has warned.

The characteristic red cheeks and nausea are a well-recognized phenomenon, but few people are aware that the underlying enzyme deficiency also predisposes heavy drinkers to squamous cell esophageal carcinoma, say the researchers.

With some 36 percent of East Asians displaying the flush response, there is potential to save “a substantial number of lives” by counseling affected individuals against heavy drinking. [PLoS Med 2009 Mar 24;6(3):e50]

"Cancer of the esophagus is particularly deadly, with 5-year survival rates ranging from 12 to 31 percent throughout the world,” said lead researcher Dr. Philip Brooks, of the US National Institute on Alcohol Abuse and Alcoholism. “And we estimate that at least 540 million people have this alcohol-related increased risk for esophageal cancer.

"We hope that by raising awareness of this important public health problem, affected individuals who drink will reduce their cancer risk by limiting their alcohol consumption," he said.

Flushing is caused by a deficiency in aldehyde dehydrogenase 2 (ALDH2) – an enzyme which breaks down acetaldehyde, a carcinogenic by-product of ethanol metabolism. People with normal ALDH2 function can convert acetaldehyde safely into acetate, but in ALDH2-deficient individuals it accumulates in the body, leading to facial redness, nausea and tachycardia.

In people who are homozygous for the ALDH2-deficiency gene, the response to alcohol is so unpleasant that they cannot consume large quantities, and are thereby protected from the associated risk of esophageal cancer.

Heterozygotes, however, can develop tolerance to acetaldehyde and may become heavy drinkers. Studies from Japan and Taiwan have shown that ALDH2-deficient heterozygotes who drink heavily are over ten times as likely to develop esophageal cancer, [Jpn J Clin Oncol 2003 Mar;33(3):111-21; Int J Cancer 2008 Mar 15;122(6):1347-56]

Dr. Michael Wang, a radiation oncology consultant at the National Cancer Centre Singapore, agreed that the link between flushing and esophageal cancer is not likely to be common knowledge among doctors.

“From the article, it is fair to comment that there is a causative relation between deficiency of the gene and increased risk of esophageal cancer,” he said.

“However, there has been a lot of material published since the 1970s regarding this condition. This relationship may be confounded by smoking, which is also related to esophageal cancer. Before we say something drastic like ‘people who flush when drinking have a higher risk of contracting esophageal cancer,’ we should research all the previously published articles first.”
Wang added that all heavy alcohol drinkers should be counseled, since drinking also predisposes to other medical conditions and to drink-driving.

The study authors advise clinicians to determine whether East Asian patients are ALDH2 deficient by asking simple questions about their history of flushing when drinking alcohol. Identified flushers should then be advised of their cancer risk and encouraged to moderate their consumption, they say.

Japanese CPR success could light the way for Asia

Medical Tribune May 2009 P10
David Brill

Japan’s “impressive” success at tackling out-of-hospital cardiac arrests could inspire other Asian countries to improve their own survival rates, according to the chairman of the Singapore Heart Foundation (SHF).

One-month survival after a witnessed ventricular fibrillation episode has risen from 15 to 31 percent since a program was implemented in Osaka in 1998, researchers reported recently in Circulation. [2009;119:728-734] Neurologically-intact 1-month survival has risen from 6 to 16 percent.

The initiative has also reduced delays in calling for medical services, initiating cardiopulmonary resuscitation (CPR), and delivering a first shock, the study shows.

In Singapore, just 2.7 percent of people currently survive following an out-of-hospital cardiac arrest (OHCA), according to the SHF, which launched its own CPR initiative last year.

“This is a very encouraging study because it inspires us to put more effort into CPR training and providing defibrillators,” said SHF chairman Associate Professor Terrance Chua.

“What is most impressive is that they were able to improve survival rates. Having this clear documentation is good for morale because otherwise you can commit a lot of resources without knowing how much benefit you are getting from it,” he said. “We really take our hats off to them for having done this in a prospective registry so that they can monitor the improvements.”

The Utstein Osaka Project focuses on a four-step “chain of survival,” comprising activation of emergency medical services, CPR, defibrillation and advanced life support measures given by healthcare providers. The survival benefits were driven largely by improvements in the first three links of the chain, suggesting that the program’s public education component has had a significant impact.

Some 120,000 citizens per year have been trained in conventional CPR since the introduction of the program in Osaka, covering an area with a population of 8.8 million.

“This study proves that improvement in the chain of survival results in increased survival from out-of-hospital cardiac arrest in the real world,” said Dr. Taku Iwami, an assistant professor at Kyoto University Health Service, who led the research.

“We need to increase the number of automated external defibrillators [AEDs] in public places as well as train people in not only CPR but in the use of AEDs,” he said. “In many areas of the world, there are serious delays in the use of CPR and AEDs. We hope this study encourages other emergency medical service systems to start or continue their efforts to improve based on objective data.”

The study included 42,873 OHCAs in which resuscitation was attempted, occurring from May 1998 to December 2006. The median time from collapse to call for medical attention dropped from 4 to 2 minutes, and the time from collapse to first CPR dropped from 9 to 7 minutes. Median time from collapse to first shock decreased from 19 to 9 minutes.

In Singapore the public response to learning CPR has so far been “pretty positive,” according to Chua, who noted that despite the improvements in Osaka’s survival rates the study still highlights that there is further room for improvement.

The SHF launched its 3A (Anyone, Anytime, Anywhere) program in November 2008. The project includes the provision of CPR kits which include a mannequin, DVD and other reference materials, all of which can be used at home with the intention of creating a ”multiplier effect” whereby CPR skills are passed on to friends and family.

Thailand and Indonesia have also expressed an interest in adopting similar programs, Chua said.

The SHF has already trained some 2,000 students from seven schools using the CPR kits, which are on sale at a subsidized price of S$20 for students and S$50 for corporations and communities.

Several commercial facilities, including Suntec City and VivoCity shopping centers, have already installed their own AEDs since the launch of the 3A program, according to Chua. Changi Airport has also backed the project, and is currently in the process of developing and implementing its own AED installation program.

A 2002 study from three airports in Chicago, US, reported that 11 out of 18 patients who arrested with ventricular fibrillation over a 2-year period were successfully resuscitated using AEDs. Ten were alive and neurologically intact a year later. Six of the 11 rescuers had never used an AED before, although three were medically trained. [N Engl J Med 2002 Oct 17;347(16):1242-7]

Everolimus shows promise for advanced stomach cancer treatment

Medical Tribune March 2009 P9
David Brill

Everolimus could provide a viable new treatment option for advanced gastric cancer, Japanese investigators said recently, following the conclusion of a phase II trial of the drug.

After 8 weeks of therapy everolimus halted tumor growth in 55 percent of patients, with 45 percent showing signs of tumor shrinkage.

A phase III trial involving some 500 patients will open for enrollment later this year, the drug’s manufacturer, Novartis, announced following the presentation of the new data at an American Society of Clinical Oncology symposium in January.

The multicenter, open-label study involved 54 Japanese patients of Asian descent who had previously undergone heavy treatment with chemotherapy.

"There are very limited treatment options for patients who progressed despite the standard treatment for this aggressive cancer," said lead researcher Dr. Atsushi Ohtsu, director of the Research Center for Innovative Oncology at the National Cancer Center Hospital East, Chiba, Japan. "The results from this study demonstrate that [everolimus] has the potential to provide an effective new option for these patients."

Patients in the study took 10 mg oral everolimus daily for an average of 57 days. The overall rate of adverse events – including anorexia, vomiting and stomatitis – was around 10 percent, with serious adverse events occurring in some 3 percent.

The median progression-free survival with everolimus was 83 days. At 4 months, around 30 percent of patients were still progression-free.

Everolimus inhibits the mammalian target of rapamycin (mTOR) – a cell signaling protein which is implicated in the development of several cancers. The drug has already shown promise for advanced renal cancer carcinoma and is currently under regulatory review in Europe and the US for this indication. A phase III randomized controlled trial, published last year, found that the drug prolonged progression-free survival by a median of 2.1 months over placebo in patients with metastatic renal cell carcinoma. [Lancet 2008 Aug 9;372(9637):449-56]

Gastric cancer is the most common type of cancer in East Asia, accounting for 18.9 percent of new cases in 2007, according to data from the American Cancer Society. Globally, it is the second leading cancer and is responsible for some 866,000 deaths worldwide each year, according to the WHO.

The risk of gastric cancer is thought to be increased by eating a diet high in salted, pickled and smoked foods, and by long-term infection with Helicobacter pylori. Male gender, smoking and age above 50 are also important risk factors.

NUS to receive $3.5 million oncology funding boost

Medical Tribune December 2008 SFIII
David Brill

Singapore’s rapidly-expanding cancer research field has received a further boost with the recent signing of a $3.5 million deal for translational research.

The agreement will see the National University of Singapore’s (NUS) Yong Loo Lin School of Medicine embark on three joint projects with Bayer Schering Pharma, the Germany-based pharmaceutical company.

One of the aims is to profile new cancer drugs within Asian populations, where certain types dominate in comparison to the West.

The deal with NUS is just the first stage of a larger project for Bayer, which intends to invest S$20 million over the next 6 years in research and development in Singapore.

The focus of the present deal is on gastric, liver and lung cancer, but future projects could extend to other cancer types, said Associate Professor Manuel Salto-Tellez, assistant dean of research at NUS.

"We are very proud of this collaboration and believe that the partnership will have significant benefits for patients, academia and industry alike," he said.

"Some of the drugs that are currently with patients have taken up to 20 years to
be developed. By linking with industry in this way we’ll be able to make this process faster. What we are doing is at the core of what our institution is supposed to do, which is to serve patients better."

The project also seeks to identify new predictive biomarkers and to study new clinically-relevant tumor models.

Oncology research in Singapore is booming, with collaborations between academia and industry apparently on the rise. Another deal, signed in August, will see AstraZeneca provide promising new compounds for clinical and preclinical trials at National University Hospital and the National Cancer Centre Singapore.

"We are facing a big problem because cancer is one of the biggest killers in Singapore and the incidence continues to rise," said Salto-Tellez.

"Soon it’s going to develop into an extraordinary contradiction where the majority of cancer patients will come from Asian countries, yet the knowledge of the patients and how to treat them will be based on the results from other parts of the world and other ethnicities. Thus we cannot overemphasize how important it is to build clinical and scientific knowledge in Asia that will be directly and immediately applicable to Asians," he said.

Asia: The new frontier for cancer research

Medical Tribune November 2008 P2-3

Dr. Foo Chuan Kit, Bayer Schering Pharma’s medical director for South Asia and Hong Kong, addresses the importance of tackling cancer in Asia.

Asia is facing a population explosion which will change the global disease landscape. Sixty percent of the world’s inhabitants – some 4 billion people – currently live in Asia, with 40 percent in China and India alone. By 2050, the continent’s population is predicted to rise to a staggering 6.5 billion people.

As the population continues to grow it is also continuing to age. In 2005 just 10 percent of Asians were aged 60 and above; by 2050 this figure will be closer to 28 percent, with Japan and Singapore expected to have the world’s highest proportions of over-80s.

With these trends emerging it is no surprise that cancer rates are climbing fast. Asia is facing a new epidemic, and it will not be long before the majority of the world’s cancer patients will be living in the continent.

In the face of this threat there is an urgent need to redress the global balance of cancer research. Most clinical trials continue to take place in the US and Europe, yet there are many important differences in the evolution of the disease between continents which demand further investigation.

The distribution of cancer is different in Asia, where certain types predominate in comparison to the West. Stomach cancer was the most common newly-diagnosed cancer in East Asia in 2007, yet did not feature in the top four most common types for North America or Northern and Western Europe. Liver cancer is particularly common in both East and South-East Asia, with lung, breast, colorectal and nasopharyngeal cancers also highly prevalent in these areas.

For men, according to 2002 data, prostate is the most common cancer type in the US, Australia and most of Europe, yet lung, liver and oral cancer dominate in Asia. Breast cancer is the most common type for women in most countries worldwide whereas in China stomach cancer is the most prevalent. In India and several other South and South East Asian countries cervical cancer is the most common type among women.

Understanding the reasons for these discrepancies is an important emerging area of investigation. Liver cancer in Asians, for example, is largely caused by hepatitis B, whereas hepatitis C and cirrhosis from alcohol abuse are more common causes among Caucasians. For nasopharyngeal cancer, a higher prevalence has been observed in Southern Chinese than in Northern Chinese, so there appear to be intra-ethnic differences as well. For other cancers, however, these regional variations and their explanations remain unclear.

These geographical differences also raise interesting questions as to the efficacy of cancer drugs in Asian patients. Gefitinib, for example, yielded disappointing results in clinical trials of western adenocarcinoma patients but was recently shown to be effective in non-smoking Asians with this cancer.

The optimal dosing for Asian patients is another important area of research. Docetaxel and carboplatin for example, appear to induce more side effects among Asian lung cancer patients than among Caucasians, and the dosages need to be adjusted accordingly. The response to these drugs also seems to be higher among Asian patients, but more research is still needed to better understand these observed differences.

With so many unanswered questions the need to invest in Asia is greater than ever. At Bayer Schering Pharma we have committed S$20 million over the next 6 years into research in Singapore alone. In Asia Pacific as a whole we enrolled less than 100 patients in clinical trials in 2005; by the end of 2007 we had 3,700 patients participating in 64 different trials.

The growing investment from pharmaceutical companies is great news for Asia. The increasing number of research collaborations, such as our recently-signed agreement with the National University of Singapore, will give patients unprecedented access to exciting new drugs. The increasing focus on translational research, meanwhile, will help to minimize the time from bench to bedside, enabling new compounds to enter clinical trials as early as possible. The recruitment of patients also seems to be quicker in Asia Pacific, with our data suggesting that the enrollment process here is twice as fast as the global average.

As our understanding of cancer in Asia improves so too will our treatments. This investment in Asia-specific research must be sustained in order to strengthen our defences in the face of the future epidemic.

Asian women less aware of long-term risks after gestational diabetes

Medical Tribune November 2008 P6
David Brill

Asian-born women who experience gestational diabetes mellitus (GDM) during pregnancy may be less acutely aware of their subsequent risk of developing diabetes, according to an Australian study.

A large postal survey of women with a history of GDM revealed that 92.3 percent knew that the condition predisposes to later development of type 2 diabetes.

Less than 30 percent of the 1,176 respondents, however, considered themselves to be at high or very high risk.

Risk perception was particularly low among Asian-born women, with just 15.5 percent believing themselves to be at high risk – a significantly lower proportion than Australian-born women (P=0.013).

“This is of some concern considering that evidence suggests that this may be in fact the highest-risk group,” said Ms. Melinda Morrison, a pediatric diabetes dietician who presented the study findings.

“We’re talking about Asian women in Australia so it may be down to how the messages are getting through, as well as possible cultural differences,” she said.

She added, however, that the data have yet to be fully analyzed so it is difficult to speculate on possible explanations for the finding at this point.

American Diabetes Association guidelines identify Asians as a high-risk population for GDM. [Diabetes Care 2000 Jan;23 Suppl 1:S77-9] A study of 2,797 Asian pregnancies found that the incidence of GDM was 10.6 percent for Vietnamese women, 9.2 percent for Chinese women and 8.6 percent for Filipino women. [Diabetes Care 2001 May;24(5):955-6]

GDM affects between 3 and 8 percent of pregnancies in Australia, according to Morrison, who is based at the New South Wales section of the charity Diabetes Australia.

With these women at substantially higher risk for developing diabetes this group represents an important target for disease prevention through lifestyle modification, she said.

“Often these women really only have contact with their GP after pregnancy and are no longer in the system of diabetes care necessarily, so it is over to the GP to help them make those changes and raise that awareness,” she said.

Diabetes conversation tool set to launch in Asia

Medical Tribune November 2008 P9
David Brill

A new interactive tool to help educate patients about diabetes is due to be unveiled in Asia next year.

The Diabetes Conversations programme provides healthcare professionals with a set of materials designed to engage patients in learning about the disease and making decisions around their treatment.

The packs, which are available free of charge, will be translated into more than 25 different languages and tailored to individual countries in order to make them culturally relevant.

The European version, developed in collaboration with the International Diabetes Federation Europe and sponsored by Eli Lilly and Company, was unveiled at the EASD in September. The Asian and Latin American editions, however, are expected to remain in development until December this year.

“It is increasingly up to GPs and primary care practitioners to educate patients, so having effective tools that they can leverage is becoming more and more important,” said Mr. Peter Gorman, a representative of Healthy Interactions Inc, the US-based company who manufacture Diabetes Conversations.

Healthcare professionals will be able to register for free training in how to use the materials, which include activity cards and table-top conversation maps.

These can then be used in small group sessions of three to 10 patients at a time, typically lasting around 45 minutes to an hour.

A similar version was launched in the US last year in conjunction with the American Diabetes Association. More than 14,000 healthcare professionals have already been trained in using the conversation tool, Gorman said, adding that the programme has been “extremely successful” so far.

“A lot of healthcare professionals recognize that having a Powerpoint presentation or a flip chart up in front of a group isn’t a very engaging way to get patients involved in education. That’s really the selling point of these – do you want to engage the patient and have them own their outcome?” he said.

Asia takes action on drug-resistant tuberculosis

David Brill
The Lancet Infectious Diseases October 2008
Article link

This article also appeared on the Stop TB homepage of the WHO's Western Pacific Region Office.

Africa and eastern Europe have largely dominated recent attention around strengthening tuberculosis control, but Asia could yet prove the decisive battleground in the international war on the disease. At a gathering of countries from WHO's Western Pacific Region (WPR) in Tokyo (July 22—24) Pieter van Maaren, regional advisor for tuberculosis (WHO, Manila, Philippines), accused Asian nations of complacency, saying: “if we are going to avoid a public-health disaster, we have to accelerate action”. Representatives from all eight of the countries that attended—representing around 95% of the region's multidrug-resistant (MDR) tuberculosis burden—acknowledged the issue and agreed to raise their commitment to it.

The WPR alone makes up a quarter of the world's tuberculosis cases—a similar proportion to Africa. Together with the South-East Asia Region (SEAR), more than 300 000 cases are estimated to be MDR, with only 1% of patients accessing appropriate treatment. The prevalence of MDR tuberculosis is highest in China (one in every ten new tuberculosis cases), which remains second only to the former Soviet Union in terms of prevalence.

Strengthening diagnostic laboratory facilities is a major component of WHO's strategy for the control of MDR tuberculosis in the region. Senior laboratory managers from the WPR will be attending a workshop in Hong Kong in October to discuss how to implement the latest technologies, including molecular line probe assays that can give a diagnosis of MDR tuberculosis in 2 days. These tests are being introduced through a UNITAID-funded project, announced in June. Laboratory capacity is a serious concern in the SEAR, which is home to only two of the 26 centres in WHO's global Supranational Laboratory Network, a network that provides assistance with MDR-tuberculosis testing to national facilities.

“For us in this region the emphasis is on using this window of opportunity to put in cost-effective interventions to prevent MDR tuberculosis. It's less about trying to catch people once they've developed MDR disease, which is what we are seeing in eastern Europe and in Africa, but rather building that barrier to stop people developing MDR tuberculosis in the first place”, said Nani Nair, SEAR's regional tuberculosis advisor (WHO, New Delhi, India).

In Tokyo, delegates also promised to commit to providing better access to treatment, with countries being encouraged to submit proposals to the Global Fund to finance the purchasing of drugs for MDR tuberculosis. Management programmes supported by the Green Light Committee are currently operating in six SEAR countries, while UNITAID funding is available for drug procurement in three.

Nair told TLID: “…if all current plans can be implemented successfully then the long-term outlook for control of MDR in the SEAR is very good”. At present, however, she estimates that only half the required budget has been raised. The region does not contain any major international donors, and to make up this shortfall countries must rely on funding from their own governments, donors from other regions, and international initiatives such as the Global Fund and UNITAID.

China meanwhile is looking into health-care reforms and how they can be integrated into scalable new programmes for MDR-tuberculosis treatment and control. In the wake of the severe acute respiratory syndrome epidemic in 2003 it became a legal requirement for health-care systems to report all new tuberculosis cases within 24 h. Individual patients from across the country are now entered into an online database and can be tracked centrally to ensure that they receive appropriate treatment.

The project has caught the attention of the Bill & Melinda Gates Foundation, who have pledged to spend some US$900 million on tuberculosis worldwide by 2015. Representatives from the Foundation have been in discussions with the Chinese government about how new diagnostic technologies can be integrated into this system to detect multidrug resistance at the first point of contact. “Their surveillance system is phenomenal, and they've scaled it up so that 90% of their referral hospitals are using it. Having these online mechanisms for tracking tuberculosis cases and ensuring that those patients get optimal therapy lays the foundation for a truly innovative programme for controlling MDR tuberculosis that goes beyond the standard interventions”, said Senior Program Officer for Tuberculosis Peter Small (Bill & Melinda Gates Foundation, Seattle, WA, USA), who recently returned from a fact-finding trip to the country. He added that he was “very impressed by the government's commitment” to tackling MDR tuberculosis.

How current efforts to control MDR tuberculosis in Asia will affect the longer-term global spread of the disease remains to be seen. Small is in no doubt, however, as to the importance of the task. “What the world is doing with MDR tuberculosis right now, through inaction, is committing ourselves to a future epidemic of much more complicated tuberculosis. I suspect that future generations will judge us harshly if we fail to intervene”, he said.

Images courtesy of WHO/P Virot.

Asia-Pacific researchers launch trial for combined liver cancer therapy

Medical Tribune August 2008 SFIX
David Brill

An international team of researchers has begun a study into a combination therapy that could prolong the lives of patients with inoperable hepatocellular carcinoma (HCC) – a cancer that is particularly common in Asia.

Thirty one patients will participate in the 2-year phase I/II trial, which aims to combine the oral chemotherapy drug sorafenib (400mg twice daily) with radiation therapy delivered by Selective Internal Radiation (SIR)-Spheres®.

The primary objectives are to assess the tumor response rate and the safety and toxicity of the therapy. Survival, recurrence rates and quality of life are among the secondary outcomes to be investigated.

The study is being carried out by The Asia-Pacific Hepatocellular Carcinoma Trials Group, which is based at the National Cancer Centre Singapore (NCCS). Centers in 12 different countries, including Malaysia, Indonesia and Philippines, have so far been invited to participate.

Professor Soo Khee Chee, director of the NCCS, said that the team was “especially pleased” to announce the trial, adding that he was confident it would produce very strong data.

“This trial is an important milestone for all our researchers and clinician investigators because we will be taking a step forward in our efforts to help our patients combat liver cancer,” said Soo.

The chair of the trial, Associate Professor Pierce Chow, said that HCC is particularly prevalent in Asia owing to high rates of hepatitis B, which is the major cause of the cancer. He said that there was anecdotal evidence to suggest that the combination therapy was promising for HCC patients, but added that it is imperative that scientific data be gathered appropriately from clinical trials.

The high cost of the two treatments is also an important consideration according to Chow, who is a senior consultant surgeon at Singapore General Hospital. Sorafenib costs a patient around S$9,000 per month at NCCS, whereas SIR-Sphere therapy could cost up to S$20,000, he said.

Funding for the trial comes in the form of a S$468,200 grant from Singapore’s National Medical Research Council. Bayer Schering Pharma Singapore, who produce sorafenib, and Sirtex Medical Ltd, who manufacture the SIR-Spheres®, are each providing around S$1.5 million worth of therapeutics.

Sorafenib targets the proliferation of tumor cells and angiogenesis. Data from a Phase III trial, presented in 2007 at the annual meeting of the American Society of Clinical Oncology, showed that the drug extended overall survival in inoperable HCC patients by a median of 3 months but did not induce tumor regression.

SIR-Spheres®, conversely, induce a significant tumor response but trial data have yet to demonstrate an improvement in survival rates Chow said. The therapy involves delivering very high dose radiation directly to the tumor via a catheter, thereby sparing the healthy surrounding tissues.

New bird flu vaccine promises broad immunity and rapid manufacture

Medical Tribune August 2008 SFXII
David Brill

A new vaccine against the avian influenza H5N1 virus has been shown to be well tolerated and induce high levels of immunogenicity against a variety of strains.

The vaccine is derived from continuous cell culture and could be produced up to 3 months quicker than by using traditional methods, the manufacturers suggest.

Mr. Peter Carrasco, Policy Advisor on Vaccine Security for WHO, said that the vaccine could be useful for protecting against viruses that are currently circulating in infected birds, but added that more research is needed with larger study groups to reconfirm the trial’s findings.

The vaccine was tested in a randomized phase I and II trial involving 275 subjects who received two doses 21 days apart. The results were published in The New England Journal of Medicine.

A dosage of 7.5 mcg without adjuvant induced a neutralizing-antibody response in 76.2 percent of subjects – equivalent to a seroconversion rate of 69 percent. Immunogenicity was seen not only against the clade 1 strain used to produce the vaccine (A/Vietnam/1203/2004), but also extended to the clade 2 and 3 strains.

Conventional H5N1 vaccines are produced using embryonated chicken eggs – a technique that requires the use of an attenuated version of the virus. Cell culture, however, can be used to generate a vaccine from the wild type, thereby eliminating the delay while a modified virus is produced.

“The lag time between receipt of a new virus and delivery of a new vaccine is only something like 12 weeks using our technology, which is about 3 months quicker than can be done with the egg technology,” said Dr. Noel Barrett from the Department of Global Research and Development at Baxter BioScience, who developed the vaccine.

“We’re faster, we’re more flexible, and the process is much more robust in that we’re not dependent on the supply of hen’s eggs, which is an uncertain factor in the event of a pandemic caused by an avian virus.”

Baxter have submitted a licensing application for the vaccine to the European Medicines Agency (EMEA), and expect a decision early next year.

The company has reached agreements with some countries to provide the vaccine in the event of a pandemic and already has the manufacturing capacity to deliver in a relatively short time, Barrett said. The decision whether to implement pre-pandemic vaccination remains a matter of government policy, he added.

One potential drawback to the new vaccine is the need for enhanced biosafety facilities which can handle the virulent wild type virus.

“There are very few facillities which are biosafety level 3, and these are expensive to maintain,” said Associate Professor Paul Ananth Tambyah, head of the Division of Infectious Diseases at the National University Hospital in Singapore, who was also one of the authors of the study.

“Without them it is not safe to manufacture this vaccine,” he said, adding that these manufacturing hurdles would need to be overcome before the vaccine could be used routinely.

Chronic kidney disease: Asia’s ‘silent epidemic’

Medical Tribune August 2008 P14
David Brill


Reducing chronic kidney disease (CKD) should become a public-health priority, according to the authors of a large prospective study which found the national prevalence of the condition in Taiwan to be 11.9 percent.

This figure puts the condition on a par with smoking and obesity as a leading cause of death, the researchers wrote in The Lancet.

Awareness among the study population was low – just 3.5 percent of people knew that they had CKD.

The study, which followed 462,293 people over 13 years, also found that CKD is much more prevalent among lower socioeconomic groups, and that the regular use of Chinese herbal medicines carries a 20% increased risk for developing the condition.

“I think this is a silent epidemic,” said the study’s lead author Dr. Chi Pang Wen, from the National Health Research Institutes in Taiwan.

“It’s growing globally, and particularly Asians need to be even more concerned because of our fondness of taking medicine, including Chinese herbal medicine. The seriousness of this has not been well appreciated because people are only looking at the tip of the iceberg, which is the people on dialysis,” he said.

People with CKD were twice as likely to die from cardiovascular causes and 1.83 times as likely to die from any cause, the study found. Almost 40 percent of those who died were aged less than 65. [Lancet 2008 Jun 28;371(9631):2173-82]

The study highlights the importance of modifying risk factors such as hypertension, diabetes and smoking said Wen, who noted that the kidneys seem to be the earliest warning signal for vascular problems that may lead to cardiovascular death.

He called on the whole medical establishment to get involved with tackling the burden of CKD, beginning with the laboratories.

“When they report creatinine they need to have a formula to convert it into glomerular filtration rate (GFR). Without that conversion most Asian doctors are looking at creatinine which does not have as a high a level of sensitivity as GFR and cannot classify people into the 5 stages of CKD,” he said.

Wen added that the public should be encouraged to ask their doctor about their GFR value and whether or not they have proteinuria, which is an important warning sign for CKD.

Dr. Chan Choong Meng, Head and Senior Consultant in the Department of Renal Medicine at Singapore General Hospital, said: “This study shows that patients of a lower socioeconomic status are more susceptible to developing CKD. Unfortunately, they are likely to be unaware of the disease until a later stage.

“Early detection by screening and treatment for diabetes and hypertension will help reduce the burden of CKD, and early treatment will help in preventing and retarding the progression of the disease,” he said.

Chan added that the rates of CKD observed in the study are comparable to those previously documented for the US and Norway.

Aspirin alternative could benefit Chinese stroke patients

Medical Tribune July 2008 P9
David Brill

Cilostazol is as effective as aspirin at preventing stroke recurrence but carries a lower risk of brain bleeding events, according to the results of a pilot study published in The Lancet Neurology.

These findings suggest that the drug could be a safer alternative to aspirin for secondary stroke prevention, particularly in Chinese populations, which have high rates of hemorrhagic stroke and other bleeding events.

Lead author Dr. Yining Huang of the Peking University First Hospital in Beijing, said that cilostazol could be used routinely in future, but should only be given to patients at high risk of hemorrhage. He added that aspirin is more cost effective and should remain first-line treatment for the majority of patients.

The study also found that mild side effects such as headache, dizziness and palpitations were more common among patients taking cilostazol.

The researchers conducted a randomized double-blind trial comprised of 720 patients who had experienced an ischemic stroke within the past 6 months. Participants took aspirin (100 mg per day) or cilostazol (100 mg twice per day) for between 12 and 18 months. [Lancet Neurol 2008 Jun;7(6):494-499]

Over the study period seven brain bleeding events occurred in the aspirin group, compared to just one in the cilostazol group (P=.034).

Cilostazol also reduced the overall risk of stroke recurrence by 38.1 percent but this comparison was not statistically significant. The authors suggest that the small sample size and short follow-up duration meant that the study was underpowered to assess the relative efficacies of the two drugs.

Dr. Charles Siow, a consultant neurologist at the Siow Neurology Headache and Pain Centre in Singapore said: “If the study can be replicated and the efficacy confirmed in a larger study, cilostazol may be an option for stroke prevention.” Siow added that cilostazol, a phosphodiesterase 3 inhibitor, could replace aspirin in routine practice only if the issues of side effects and cost were resolved.

Stroke is a leading cause of death in China, and there is a high proportion of hemorrhagic
stroke. Research has demonstrated that stroke rates vary across different regions but are typically higher than in Western countries. [Stroke 2006 Jan;37(1):63-8]

A larger-scale multicenter trial comparing cilostazol with aspirin is already underway in Japan. Two thousand six hundred patients have been enrolled and are due to be followed up for between 1 and 5 years. Huang said that the interim results were “very positive.”

The trial is expected to finish in December this year and will be published in 2010.