Chemotherapeutic agents are well known for causing side-effects. Some agents cause more and some much less. An inability to tolerate the treatment related side-effects is a very real and legitimate reason for stopping therapy. However, are any of the experienced side-effects associated with a better disease response to the chemotherapeutic drugs?

Researchers from OSI Pharmaceuticals in Colorado, USA, recently published their analysis on the association between the development of a rash and the efficacy of erlotinib in treating patients with lung and pancreatic cancer (Clin Cancer Res 2007; 13: 3913 – 3921). [Erlotinib (Tarceva is the trade name, made by OSI Pharmaceuticals Inc.) is one of the new molecular targeted agents which is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. One of the side-effects of EGFR inhibitors is the development of skin rashes. This resembles acne and is characterized by papules and pustules over the scalp, face, neck and upper trunk. To some patients the acneiform rash can be quite florid and troublesome. Other EGFR inhibitors on the market include cetuximab (Erbitux, ImClone Systems Inc.) and panitumumab (Vectibix, Amgen Inc.). These agents are now an important part of what a medical oncologist can use to treat patients with inoperable colon, lung, pancreas and breast cancers.] These researchers compared the outcome of patients who did or did not develop rash while taking erlotinib for (1) non-small-cell lung cancer in the National Cancer Institute of Canada Clinical Trial Group Study BR.21 and (2) pancreatic cancer in the National Cancer Institute of Canada Clinical Trial Group Study PA.3. In the lung cancer study, patients either received a tablet containing erlotinib or one without erlotinib (called a placebo). In the pancreas cancer study, the patients either received gemcitabine + placebo or gemcitabine + erlotinib.

The presence of a rash was associated with longer survival in both studies. The benefit was also noted to increase with the severity of the rash. In the lung cancer study group, erlotinib-treated patients who did NOT develop a rash survived a median of 3.3 months compared with 7.1 months in those with grade 1 rash and 11.1 months in those with grade 2 rash. In the pancreas cancer study group, longer survival was only associated with patients who developed a grade 2 rash. Those patients who had no rash or grade 1 rash survived a median of 5.4 and 5.7 months. The median survival of patients with a grade 2 rash was 10.8 months.

An unexpected but interesting result from the study is that some of the patients who received placebo treatment also developed a rash – 18% in the lung cancer group and 30% in the pancreas cancer group! (Rash can occur in patients who are receiving gemcitabine). In the lung cancer study group, patients taking a placebo who developed a rash had a median survival of 8.2 months compared to 4.7 months in those without a rash. In the pancreas cancer study group, the presence of a rash did not confer any survival benefit.

The development of an acneiform rash can be unsightly and unpleasant for some patients. This is probably more so in female patients. Knowing that the presence of a rash is an indication that your treatment is having an effect on the cancer is a boost to your morale and will encourage you to tolerate the side-effects better. However, to some patients, this rash is just too much for them. Irrespective of the reasons why a patient cannot tolerate the side effects of the treatment, we, as doctors, have to respect the patient’s wishes ultimately. You, as relatives or loved ones, have to respect the patient’s wishes too. Though the urge to encourage your loved one to continue with the treatment is strong, there are times when we have to accept the patient’s decision to stop therapy.

As to why those patients who developed a rash taking placebo had a longer survival period, no one knows. A possible explanation is that the rash is a side effect of your immune system having an effect on the cancer itself. Though this is not applicable to everyone and to all cancers, sometimes we do see wonders. That’s when I feel humbled and have a reflective moment about how powerful and mysterious Mother Nature can be!

In developed countries, we take piped, clean water for granted. Most of the time we can drink it straight out of the tap and we don’t have to worry about getting a bad bout of diarrhea. No bacteria, great! But, does it contain anything which can cause ill-health years later?

A study from Santiago, Chile, looked at the long-term health effects of drinking water contaminated with arsenic (J Natl Cancer Inst 2007; 99: 920 -928). In 1958, the average water concentration of arsenic in Region II (the second most northerly administrative region) of Chile went up dramatically. The arsenic content stayed high until the 70’s when water treatment plants were installed.(Chronic ingestion of arsenic will cause skin, lung and bladder cancers.) The researchers studied the lung and bladder cancer deaths occurring in region II and region V of Chile. (Region V’s drinking water is not contaminated with arsenic.) Compared to region V, the death rate from lung and bladder cancer in region II residents started to rise about 10 years after their exposure to the high arsenic content in drinking water. The death rate continued to rise and did not peak until 1992 -1994, a clear 20 odd years after the water was made safe by treatment. The lung cancer mortality rate for residents in region II was 3 times higher than those in region V. Compared to region V, the region II men and women were 6 and 13 times, respectively, more likely to die from bladder cancer.

Arsenic contamination of groundwater is a serious problem in the Ganges delta of Bangladesh and West Bengal, India. However, parts of Thailand, Taiwan, Argentina and China are also affected. Surprisingly, parts of United States have arsenic in their groundwater. In 1942 the United States Public Health Service set the upper safe limit of arsenic content in the drinking water at 50 microgram per litre. Twenty years later, the US Public Health Service had identified 10 microgram per litre to be its ultimate goal. In 1992, the World Health Organization Guideline defined the safe arsenic concentration in drinking water to be 10 microgram per litre.

The Environmental Protection Agency (EPA) of USA studied the pros and cons of lowering the 50 microgram limit. In the dying days of the Clinton administration in January 2001, it decided to set the new standard at 10 microgram per litre to take effect in January 2006. The incoming Bush administration suspended the new regulation. Fortunately, after months of study by the new EPA administrator, the new standard was accepted and to take effect from January 2006. In USA, many public water supply systems obtained their water supply from groundwater which meets the 50 microgram per litre arsenic standard but not the 10 microgram per litre limit. It has been estimated that 35% of water supply wells in Arizona and 38% in California would fail to meet the new limit of 10 microgram per litre.

With increasing mining activities world wide, the cleanliness of groundwater is constantly being threatened. Some mining processes require the use of various noxious chemicals to recover the metal being mined. For example, in our quest to mine gold from Mother Earth, we use mercury and cyanide to recover gold from the ore. Both mercury and cyanide can cause serious health problems. Cyanide spillage has been documented to kill and to contaminate the river system downstream. Mercury damages the brain, kidneys and endocrine system. Chronic exposure to mercury leads to symptoms such as ataxia, numbness in the hands and feet, general muscle weakness, contraction of the visual field and damage to hearing and speech. In extreme cases, insanity, paralysis, coma and death follow within weeks of the onset of symptoms. This constellation of symptoms and signs was named Minamata disease, first described in residents who lived around the Minamata Bay in Japan and innocently consumed the mercury contaminated fish and shellfish from the bay.

While it is inevitable that the burgeoning economies of developing countries have an insatiable appetite for all sorts of minerals to fuel their development, lets not forget that in our haste to ‘get ahead’ and become developed, we may well be storing up troubles for the future generations. If we are not careful, clean uncontaminated groundwater may become more valuable than crude oil in the future!

On 1^st July England slammed the door on smoking in bars, workplaces and public buildings, thus, bringing it into line with the rest of United Kingdom. The move has been hailed by the protagonists as the biggest boost to public health since the creation of the National Health Service in 1948. Of course many would not agree with this measure. David Hockney, an artist in England, who has been waging a campaign against the ban, has called this ‘a grotesque piece of social engineering’ imposed by a ‘political and media elite’. The pop singer Joe Jackson, who moved from USA to England when the smoking ban was introduced there, has decided to migrate from England to Germany because he still wants to ‘light up’ in public places. Indeed, while being interviewed on BBC World Service he maintained that there is no evidence that second-hand smoking has killed anyone.

Over the past week, an international conference on how to get the world to kick the habit of smoking took place in Bangkok. The World Health Organization (WHO) experts estimated that one billion people will die of tobacco-related diseases this century unless something is done about preventing smoking. According to the WHO Tobacco Free Initiative, smoking kills 5.4 million people/year and half of them are in the developing countries. The smoking rates in many developing countries are rising, especially among teenagers. With this rising rate, the annual death toll from smoking is expected to reach 8.3 million within the next 20 years. If measures such as aggressive taxation, banning cigarette advertising and making offices and public places totally tobacco-free were introduced, the smoking rates could halve by 2050. This translates into 200 million lives saved. In Thailand the smoking rate was 30% in 1992. Following the introduction of a ban on all domestic tobacco advertising 15 years ago, the smoking rate has fallen to around 18%. A spokesman for the Thailand Health Promotion Institute attributed this fall to increasing taxation on tobacco, the advertising ban and smoke-free public places.

Researchers from the University of Sydney performed a meta-analysis on 21 published studies on the association between environmental tobacco smoke exposure and the prevalence of serious lower respiratory tract infections in infancy and early childhood (Pediatr Pulmonol 1999; 27: 5 – 13). The analysis showed that the risk of having a serious respiratory tract infection in early life that requires hospitalization is doubled in a child of a parent who smokes. A study from Harokopio University in Athens investigated the relationship between chronic exposure to second hand smoke (SHS) and recurrent health events in 2172 patients who had just had a heart attack (Heart 2007; 93: 309 – 312). Of these, there were 1003 patients (46%) who had been exposed to SHS. Patients who experienced SHS exposure had a 61% higher risk of either being readmitted for or dying from coronary heart disease. An animal study from the University of California examined the effects of SHS on the biological processes in the development of atherogenesis (hardening of the blood vessels). SHS decreased the high density lipoprotein (HDL, commonly known as the good cholesterol) level in the blood and also decreased the ratio between HDL and low density lipoprotein (LDL, commonly known as the bad cholesterol), triglycerides and total cholesterol. This change in the lipid profiles not only led to more lipid accumulation in the aorta but also lipid deposition in many of the smaller blood vessels of the heart and also in liver cells (hepatocytes). This potentially can lead to more heart attacks and fatty liver respectively (BMC Cardiovasc Disord 2007; 7: 1).

The evidence that smoking and SHS is deleterious to health is irrefutable. Ironically, one day after the start of the international conference in Bangkok, Philip Morris International announced the launch of a new cigarette in the Indonesian market. The new product, called Marlboro Mix 9, is a Marlboro cigarette flavoured with cloves called kretek. About two thirds of adult males in this country of 230 million people smoke and 90% of smokers in Indonesia choose cigarettes blended with kretek. To Philip Morris International, this is purely a business strategy – a move to gain market share, a dollars and cents decision. To the smokers, this is a means of instant gratification. If you develop a tobacco related health problem, who is going to pay – both physically and financially? If you were asked to choose between a smoking ban in public places or allowing smoking in all places, which would you choose? I know what I would do.