Perhaps not everyone knows that…

Annals of Oncohgv 12 1499-1503.2001

News Once again: Natural is not benign PC-SPES (Prostatic Cancer and 'hope' in Latin) is a mixture including liquorice, chrysanthemum, isatis, Ganoderma lucidinum, pnax pseudo-ginseng, Rabdosia rubescens, palmiteus et scutellana) sold in the US without FDA control and used by prostate cancer patients because of its estrogenic actions The New England Journal of Medicine of 18 Octber reminds us again that plants are not benign as a patient suffered from a hemorrhagic syndrome related to this 'natural medicine'

The sorcerer's apprentice Many will remember Paul Dukas' music as illustrated by Walt Disney in Fantasia. Humanity has been imitating this Mickey Mouse figure for a long time and now the terrible events that are happening remind us of the reality of the risks which were taken Bacillus anthracis in its cutaneous form is a relatively benign disease, but pulmonary anthrax is devastating and lethal. It is not transmitted easily or at all by direct contact, but human inventiveness has allowed the development of antibiotic-resistant varieties which can be sent around in the mail or potentially aerosolized in air-conditioning systems, as we all have read Penicillin, ciprofloxacin, tetracyclines and erythromycm are the antibiotics of choice, best determined according to the antibiogram of the strain that is isolated Anne Crisinel in Le Temps of 17 October explains why anthrax has been chosen as a bacteriological weapon. It is easy to cultivate, it is moderately heat, light and dryness sensitive, and it is easy to put in suspension in an aerosol The spores of anthrax can be kept in a lyophilized state for up to 50 years and are still infective The WHO has a list of 44 virus, bacteria, protozoa and fungi which have most of the necessary characteristics to be used as a weapon. Until recently it was easy to obtain anthrax, just using the appropriate order forms from various laboratories that would send it around to researchers ..There is a vaccination against anthrax, that supposedly has been used by technicians in the mass-production laboratories, but the safety of the vaccination is not perfect and it takes six months before it is really active In the meanwhile governments are taking measures to be able to conduct mass vaccination campaigns again smallpox. The production of the vaccine has restarted in France after an order of Mr Kouchner, the health minister

Sleep: A need that one should not neglect Schools have restarted. Today's rhythm of life, the constant distraction of all kinds of stimulating activities, not to speak of the work pressure resulting from the use of systems which were supposed to make your life easier, such as faxes and emails, has decreased the time allotted to sleep. Adults are unfortunately not the only ones who drive themselves to exhaustion and into the hands of psychiatrists Children need from 11 to 13 hours of sleep, and an afternoon nap before the age 4 At age 13, they still should have 9 consecutive hours of sleep, but our society does not allow those whose bodies are ready to sleep later to do so, as all have to be up and around early in the morning

Swiss revolution? Switzerland's image may have been tarnished forever by the decisions taken by the banks and the indecision of the government which led to the grounding of Swissair The fact that the company had been possibly mismanaged is under investigation and even before the courts come to a decision, little doubt exists about this fact At the same time, the wise deputies have decided once again that individual physicians, not the health system by itself, including the unbelievable number of highly sophisticated University Hospitals in this tiny country, are at fault and responsible for the high costs of medicine Thus the Parliament is moving in the direction that would allow health insurance companies to decide which physicians fee's to reimburse (not the amount of the fees which one can charge, which are the same throughout the country) One wonders how insurance companies will take these decisions Physicians accepting to take care of patients with complex diseases (cancer being one) will be much more costly than others Oncologists affiliated to hospitals will be taking care of difficult cases referred to them by those who are in pure private practice Already a few years ago most oncologists were on a black list of a major insurance company, because their computer system put oncologists in the same category as endocrmologists No further comment is needed?

1500

More on the benefits of smoking Last month we reported on death and taxes, a response to the Philip Morris study of the impact of smoking on public finances in the Czech Republic We hereby give you an excerpt of 'Action on Smoking and Health' data found on the internet on 21 July 2001 A study, Public finance balance of smoking in the Czech Republic, commissioned from consultants Arthur D. Little by tobacco multinational Philip Morris has caused great controversy. The study was widely reported as showing that the savings arising from early deaths of smokers (pensions, health care, housing) outweighed their extra costs while alive (health care, absenteeism, fires). This is wrong and dangerous - a self-serving rationale for addicted smokers or protobacco politicians In fact the study itself shows the opposite, that the costs outweigh the savings by 13 times Smoking is a considerable net burden on the Czech public finances - some US$372 million (CZK 14 5 billion) per year Despite this the study does conclude, incorrectly, that smoking is a net benefit It achieves this by including tobacco taxation on the benefits side This is cheating In the absence of tobacco in the Czech economy, the government's revenue needs would be met because consumers would be spending on other goods and services that would be taxed, and in a full adjustment, the government would be taxing other things to raise the budget it requires There is a benefit to tobacco taxation because it is good economic policy to tax things that have no productive value However, this benefit equates only to any costs or inefficiencies that would be associated with raising the same sum on different tax bases - for example, VAT, incomes, profits, fuel, alcohol, waste, or energy - and that would be a small second-order benefit This is also the reason why increased tobacco taxation is a good government policy - both economically and for health The focus of media commentary and response has been on the idea that the early death of smokers is an advantage and creates savings through reduced health care expenditure, pensions and housing costs to the state For example Smoking deaths 'can help your economy' (Daily Telegraph, 18 July 2001), Smoking is cost-effective, says report (BBC, 17 July 2001), Smoking can seriously aid your economy (Guardian, 17 July 2001), Czechs Debate Benefits of Smokers' Dying Prematurely (New YorkTimes, 18 July 2001) The initial response to the report was one of condemnation of the approach. But further scrutiny reveals that the report actually shows smoking to be a considerable burden In the study, the total costs (in million CZK) attributed to smoking are given as

Cost million CZK Health-care costs Lost income due to higher mortality Absence from work ETS related health-care costs Fire Total 1 US$ = 38 8 Czech Koruny (CZK)

11,422 1,367 1,667 1,142 49 15,647

The 'benefits' due to early mortality are given as follows' Benefit million CZK Health-care savings Pensions and social cost Housing costs for the elderly Total 1 US$ = 38 8 Czech Koruny (CZK)

968 196 28 1,192

Thus the cost burden of smoking is CZK14.455 million greater than the savings - in this tobacco industry study The health costs of smoking outweigh the 'benefits' of early death by a factor of 13 It is definitely not true to say - on the basis of the Philip Morris study that the savings from dying early outweigh the costs imposed by smokers while still alive. So how do Philip Morris and AD Little manage to claim a net benefit of 5,815 million CZK from smoking? Simple1 The difference is made up of taxes raised on tobacco The argument is that smokers put more into the economy than they take out Tax income million CZK Excise tax VAT (sales tax) Corporate taxes Customs duty Total 1 US$ = 38 8 Czech Koruny (CZK)

15,648 3,521 747 354 20,270

If the tax revenues are included, then the cost benefit analysis looks as follows Cost or 'benefit' million CZK Cost of smokers while alive Savings from smokers dying early Taxes paid by smokers Net 1 US$= 38 8 Czech Koruny (CZK)

-15,647 + 1192 +20,270 +5,815

The claimed net benefit is thus CZK5.815 or US$150 million. This is flawed because including taxes in this calculation is not appropriate - this is discussed below. The costs and 'benefits' of smoking itself are real economic impacts (although highly disputable) - hospital have to be built, doctors trained, drugs purchased etc Taxes are quite different. They represent a transfer from one part of the economy to another If the Czech govern-

1501 ment did not have tobacco in its economy, there would be two main differences 1. Consumers would be spending on goods and services other than tobacco - and these expenditures would be generating taxes This would not fully replace the tax raised on tobacco because tobacco taxes account for a high fraction of expenditure 2. The Finance Ministry would raise its budget from different tax bases - income, profits, inheritance, capital gams, alcohol, fuel, waste, carbon emissions etc There are many available tax bases The total tax burden would be unchanged, but raised in a different way More accurately, without tobacco, the total tax burden (raised from all sources) would be reduced by the CZK 14,455 million net burden arising from smoking. This would be good for the economy

A great Russian scientist has died It is with great sadness that we learned that Professor Nikolai Trapeznikov, Academician of the Russian Academy of Sciences and Russian Academy of Medical Sciences (RAMS), Director of the N.N. Blokhin Russian Cancer Research Center (RCRC RAMS) died in Moscow at age 73, on Thursday, 27 September 2001 after prolonged illness He was one of the pioneers of Russian oncology and received various national or international awards and medals for his outstanding contribution to the research and treatment of cancer An eminent expert in clinical and experimental research of cancer, he served as the Director of the RCRC RAMS from 1988 till date He was one of the cofounders of the Cancer Center and promoted the Center as the head institution in research and treatment of cancer in the former Soviet Union and Russian Federation Professor Trapeznikov was most interested in bone and soft tissue tumors and he headed the unit of bone and soft tissue tumors in the Center A group of specialists under his leadership was twice awarded the State prize for science and technology of Russian Federation Professor Trapeznikov devoted a lot of his time for training of young specialists Over the last 25 years he served as the Head of the department of Oncology of the I M Sechenov Moscow Medical Academy Under his guidance 25 DSc scholars and more than 50 PhD scholars have submitted their dissertations The directors of four different cancer centers in the CIS states and 11 professors are among them. Professor Trapeznikov was the author of more than 400 scientific publications and 10 monographs in Russia and abroad His international activities were numerous Co-founder of the WHO melanoma committee, Chair-

man of the Soviet party in the Soviet-American joint committee for the fight against cancer in the 1970s, he was involved in active cooperation with UICC and collaboration between cancer centers in Eastern Europe in the 1980s More recently he expanded the boundaries of European School of Oncology to Russia and CIS, was an active Member of General Motors Cancer Research Foundation and founded the Association of Cancer Centers and Institutes of CIS

There is no 'clean war' Afghan rescue workers were on the site of a UNfunded demining office in Kabul to recover the remains of four men killed when a US missile scored a direct hit as they slept Readers of Annals of Oncology news are referred to our last month's news on the progress in demining the world Local residents are reported to have said that a cruise missile had plowed into the offices of the Afghan Technical Consultancy (ATC), which runs demining operations in one of the world's most heavily mined countries US officials have stressed that the attacks are aimed at military targets and sites linked to Osama bin Laden and his al Qaeda network, prime suspects behind the devastating 11 September attacks on New York and Washington

Appointment On 1 October, David Kerr, Editor-in-Chief of Annals of Oncology, moved from the CRC Institute for Cancer Studies at the University of Birmingham, where he had been Clinical Director since 1992, to Oxford University where he becomes the Rhodes Professor of Therapeutic Sciences and Clinical Pharmacology Dr Kerr was born and educated in Glasgow, training in medical oncology at the CRC Department of Medical Oncology of the University of Glasgow, where he worked with Prof Stan Kaye During his time at Birmingham his research activities have focused primarily on new drugs, pharmacokinetics and colorectal tumours. Recently he has developed a keen interest in gene and immunotherapy of cancer, and in 2000 he was made head of the UK's National Translational Cancer Research Network (NTRAC) which will coordinate the national infrastructure support for phase I and early phase II trials He also chairs the UK's Cancer Services Collaborative, credited by the NHS with saving some 400 years of patient waiting time Dr Kerr's move to Oxford comes with a mandate to establish a new Institute for Cancer Medicine there. In an interview Kerr commented "When they asked me to do this, I was gobsmacked At Birmingham we have consistently pursued an integrated model of drug development, with scientists and physicians working

1502 together intimately. I am convinced that this approach works, and this is what we want to continue through the new institute and through NTRAC. Really, I am delighted to have this opportunity at such an exciting time in the development of cancer research and cancer care." Dr Lesley Walker, Director of Cancer Information for The Cancer ResearchCampaign says: "The last 20 years have seen giant leaps in our basic understanding of cancer so Professor Kerr's role in bringing new cancer treatments from the lab to the clinic has never been more important. I'm really pleased for Professor Kerr and his team. We're very proud of his pioneering work at Birmingham and we hope this success will continue and grow in his new post at Oxford."

David Kerr. MD, DSc, FRCP

Perhaps not everyone knows that... ...patients with oligodendroglioma not responding to combination chemotherapy with procarbazine, CCNU and vincristine (PCV) may respond to temozolomide. This is the conclusion of a study, from University Hospital Rotterdam/Rotterdam Cancer Center, of 30 patients with recurrent anaplastic oligodendroglioma treated with temozolomide given orally at 150 to 200 mg/m2 on days 1 to 5 in cycles of 28 days. Of the 30 patients, 9 responded: 7 of 27 (26%) after prior PCV chemotherapy, and 2 of 3 who were chemotherapy naive (both with a complete response). The median time to progression in those who responded was 13 months. The authors suggest that given the ease of administration and good tolerance seen with temozolomide it is the drug of choice for patients with recurrences occurring during or after PCV therapy [1]. ... the Cancer Genome Anatomy Project (CGAP) of the US National Cancer Institute is developing publicly

accessible resources that will facilitate research at the interface of cancer research and genomics. CGAP have focused on three major areas: cataloguing genes expressed during cancer development; identifying polymorphisms in those genes; and developing resources for the molecular characterization of cancerrelated chromosomal aberrations. So far, CGAP has produced more than 1,000,000 expressed sequence tags, approximately 3,300,000 serial analysis of gene expression tags, and identified more than 10,000 human gene-based single-nucleotide polymorphisms. Now, in order to enhance access to these datasets, a new CGAP Web site (http://cgap.nci.nih.gov/) is being introduced. The site includes data for both humans and mice, and descriptions of the methods and reagents used in deriving them [2]. ... the experimental compound ecteinascidin 743 appears to function by interfering with nucleotide excision repair. Ecteinascidin 743 a compound derived from the Caribbean sea squirt Ecteinascidia turbinata, is currently being tested against a range of tumours in clinical trials. Understanding how it works might help guide the choice of which cancers it is used to treat. Nucleotide excision repair is the cellular function by which sections of damaged DNA are removed and replaced with the corrected ones. UV-light-induced skin carcinogenesis and neurodegeneration are the result of a defective nucleotide excision repair system in humans. Experimenting with human cancer cell lines resistant to ecteinascidin 743, reserachers at the US National Cancer Institute have now shown that the compound alters the nucleotide excision repair process. Theses authors suggest that rather than repairing the damaged DNA, ecteinascidin 743 causes the nucleotide excision repair machinery to create lethal breaks in the DNA, thus killing cells [3]. ... the human antimicrobial peptide (3-defensin 2 (hBD-2) inhibits the growth of Helicobacter pylori in vitro, suggesting that hBD-2 plays an antibacterial role in H. pylori induced gastritis. This is the conclusion of a study, from Nagasaki University School of Medicine, in which biopsied gastric mucosa specimens from H. pylori positive (n = 6) and H. pylori negative (n = 6) individuals were used to evaluate the antibacterial role of hBD-2 against H. pylori infection. The specimens were examined for hBD-2 expression by reverse transcription-polymerase chain reaction (RTPCR), immunohistochemistry, and in situ hybridisation. The antibacterial effect of hBD-2 against H. pylori was evaluated by determining the number of colony forming units of H. pylori after incubation with 0,10~9, 10~8, 10"', 10~b, or 10~5 M of the hBD-2 peptide. All of the H. pylori positive specimens expressed a high level of hBD-2 mRNA, but hBD-2 mRNA was not detected in the H. pylori negative specimens. Incubation with hBD-2 was found to reduce the growth rate of cultured H. pylori in a dose-dependent manner [4].

1503 ...cervical cancer screening is failing to control the disease in many developing countries Many of these countries clearly need to strengthen their capacity to diagnose and treat early forms of cervical cancer These are among the conclusions of a recent report from researchers at the International Agency for Research on Cancer in Lyon, and screening cancer prevention programmes in India They note that while some developing countries in Latin America and Asia have introduced screening over the last 30 years, these have generally achieved very limited success in controlling cervical cancer in those regions. Although some cytological screening is being carried out, there are no organized programmes and testing is often of poor quality and carried out inadequately and inefficiently among the population. As a result, there has been a very limited impact on the incidence of cervical cancer, despite the large numbers of cytological smears taken in some countries Cervical cancer incidence and mortality have fallen substantially in recent years in the industrialized world, arguably as the result of efficient screening programmes involving a cervical smear test, which can detect precursors and early forms of cervical cancer But at least 8 out of every 10 of the global total of 231,000 deaths a year occur in developing countries, where the disease remains largely uncontrolled Countries with limited health care resources cannot afford to screen frequently a wide age range of women, the authors say. Low-income countries should consider planned investments to improve capacity to diagnose and treat cervical cancer precursors and early invasive cancers in their health services before considering even limited screening programmes Middle-income countries with inefficient programmes should reorganize their programmes to target high-risk women (e g 35-49 years or 30-50 years) with the aim of a good quality and highly sensitive test once or twice in their lifetime. The authors suggest that even a once-m-alifetime test can yield a reduction of 25%-30% in incidence [5] ...spending on tobacco exacerbates the effects of poverty and causes deterioration in living standards among the poor. Addressing the issue of tobacco and poverty together could make tobacco control a higher priority for poor countries These are the conclusions of a recent report considering tobacco expenditure in Bangladesh and focusing on the potential increase in food consumption if tobacco use declined. Reviewing data from the Bangladesh Bureau of Statistics the authors found that the poorest Bangladeshis, with a household income of less than USD 24/month, were twice as likely to smoke as the wealthiest, with a

household income of more than USD 118/month. Using the money now spent on tobacco, a typical poor Bangladeshi smoker could add 500 calories to the diet of one or even two children. This change could potentially save the lives of 350 Bangladeshi children each day [6] . survey data from the US do not support the view that the use of complementary and alternative medical (CAM) therapies primarily reflects dissatisfaction with conventional care Of 831 respondents to a national phone survey and who had seen a medical doctor and used CAM therapies in the previous 12 months (in 1997), 79% believed that the combination was superior to either one alone Of the 411 respondents who reported seeing both a medical doctor and a CAM provider, only 15% typically saw a CAM provider before seeing a medical doctor Perceived confidence in CAM providers was, however, not substantially different from confidence in medical doctors Among the 831 respondents who had used a CAM therapy and seen a medical doctor, 63% to 72% did not disclose at least one type of CAM therapy to the medical doctor Reported reasons for non-disclosure of use of 726 alternative therapies, included "It wasn't important for the doctor to know" (61%), "The doctor never asked" (60%), "It was none of the doctor's business" (31%), and "The doctor would not understand" (20%) Only 14% of those giving reasons for non-disclosure to their doctor reported that they felt that the doctor would disapprove of or discourage CAM use [7]

References 1 Van Den Bent MJ, Keime-Guibert F, Brandes AA et al Temozolomlde chemotherapy In recurrent ollgodendroglloma Neurology 2001,57 340-2 2 Schaefer C, Grouse L, Buetow K, Strausberg RL A new cancer genome anatomy project web resource for the community Cancer J2001,7 52-60 3 Takebayashi Y, Pourquier P, Zimonjic DB et al Antlprollferative activity of ecteinascidin 743 Is dependent upon transcriptioncoupled nucleotlde-exclsion repair Nature Med 2001, 7 961-6 4 Hamanaka Y, Nakashlma M, Wada A et al Expression of human beta-defensin 2 (hBD-2) in Hellcobacter pylori Induced gastritis Antibacterial effect of hBD-2 against Hellcobacter pylori Gut 2001,49 481-7 5 Sankaranarayanan R, Budukh AM, Rajkumar R Effective screening programmes for cervical cancer in low- and middle-income developing countries Bull WHO 2001, 79 954-62 6 Efroymaon D, Ahmed S.Townsend J et al Hungry for tobacco An analysis of the economic Impact of tobacco consumption on the poor in Bangladesh Tob Control 2001, 10 212-7 7 Elsenberg DM, Kessler RC, Van Rompay Ml et al Perceptions about complementary therapies relative to conventional therapies among adults who use both Results from a national survey Ann Intern Med 2001, 135 344-51