As 2008 draws to a close, most, if not everyone, will be glad to see the end of 2008 and look forward to a hopefully better 2009 and calmer financial clime. For those of us who treat patients with cancer, every year we always hope for something better to come along for our patients. The recent editorial, by Drs Kelly and Venook of the University of California, in the Journal of Clinical Oncology commented on the recent availability of sorafenib (Nexavar) for the treatment of patients with advanced hepatocellular carcinoma (HCC) and how sorafenib has ‘ushered in an era of hope for patients with HCC’ (J Clin Oncol 2008; 26: 5845 – 5848).

The study showing sorafenib was effective in treating patients with advanced liver cancer was the Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP) study. The data was first reported at the American Society of Clinical Oncology (ASCO) meeting in June 2007. On the basis of these results, the drug was approved in both Europe and the United States a few months later. The SHARP study involved 602 patients, 20% positive for hepatitis B and 30% for hepatitis C. It showed that sorafenib prolonged overall survival to 10.7 months vs 7.9 months on placebo treatment (N Engl J Med 2008; 359: 378 – 390). Corroborating but different results have since been reported from an Asian trial involving 226 patients in which > 70% of them were positive for hepatitis B. The Asian trial showed that patients on sorafenib survived 6.2 months while those on placebo only survived 4.1 months (Lancet Oncol, published online 16/12/2008).

Drs Kelly and Venook wrote “This study (SHARP study) offers the first hope for life prolongation for more than 600,000 patients who die each year from HCC worldwide. With the first hope of an active therapy in a grim disease, there is a natural tendency toward expansiveness – the hype.” They say that clinicians need to question whether the patients who took part in the trial are similar to the patients they see in their office and how far the results can be generalized.

Since sorafenib was made available to all in the second half of 2007, I have, on multiple occasions, encountered patients who refused other forms of treatment and insisted on taking sorafenib alone because they heard or were told that sorafenib is effective against HCC. Unfortunately, the exact role for sorafenib in the management algorithm of HCC has not been defined yet. The data so far tells us that sorafenib, when compared to no treatment at all, can prolong life in patients with advanced HCC and good underlying liver function. It certainly has not been shown to cure patients or prolong life significantly in those with less advanced disease. In the world of finance, if you fall for the ‘hype’ around a bad financial product, you are likely to lose money. If you fall for the ‘hype’ around a new medicine, you are likely to lose more than just money.

Sorafenib has certainly given hope to patients with advanced HCC. Now there are many ongoing studies looking at how to combine sorafenib with other agents in treating other HCC patients. Lets hope these studies will bring better news to our patients in 2009. Happy New Year!

Christmas is just round the corner and most people will be attending a few Christmas lunches or dinners at work or with friends. Everyone is ready for a good nosh up and making merry, and so you should! Perhaps you might consider making it more interesting by observing who eats quickly and who eats until full, or both. ‘What for?’ you might enquire.

A study from Japan studied 4140 adults (1496 men, 2644 women), aged 30 – 69 years, living in Ikawa, a rural community in the north east of Japan, and Yao, a suburb in the south west (BMJ 2008; 337: a2002) . In this population, they examined whether eating until full, eating quickly or both are associated with being overweight (BMI ≥ 25). Overall, 50.9% (571) men and 58.4% (1265) women reported eating until full and 45.6% (523) men and 36.3% (785) women reported eating quickly (fast and very fast categories). In the eating until full group the men are 2 times and women are 1.92 times more likely to be obese when compared to those not eating until full. In the eating quickly group, both men (1.84 x) and women (2.09 x) are more likely to be obese when compared to those who did not eat quickly. As for those who eat quickly and eat until full, the risk of being overweight was 3.13 for men and 3.21 for women. This observation is not unique to the Japanese. In fact, in 1996, a study among fireman and paramedics in USA showed similar findings (Prev Med 1996; 25: 593 – 600).

Do enjoy yourself at the Christmas gathering but remember, don’t rush and don’t gorge! Have a Very Merry Christmas!

On Sunday, 14^th December, Reuters carried the news that researchers from the National Human Genome Research Institute and deCode Genetics Inc. of Iceland had found six new gene mutations linked to obesity. [deCode Genetics (DCGN) is a listed company on the NASDAQ stock exchange.]

A gene is made up of a sequence of 4 different nucleotides which code for amino acids. The researchers analysed 300,000 one-letter (= one nucleotide) mutations in the genetic code in more than 30,000 people from Iceland, the Netherlands and the United States. (One-letter mutations in the genetic code are called single nucleotide polymorphisms or SNPs.)  They cross-checked their findings in 40,000 people from Denmark and the United States and found variations in 6 genes – TMEM 18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 – which were strongly associated with body mass index (BMI).

One of the researchers from the National Human Genome Research Institute was excited by these findings as they could be a major step forward in understanding how the human body regulates weight. The CEO of deCode Genetics, however, was more excited at the prospect of using these discoveries as the first step in developing new drugs and by the fact that these new SNPs may point to valuable new drug targets.

Thirty to forty years ago, global obesity was not a major health issue. The last I checked, the human race has not made a major evolutionary change, suddenly making mankind obese an evolutionary advantage. What has changed in the last 3 – 4 decades is our lifestyle and eating habits. We have become more dependent on vehicles to get us from point A to point B. We want to be entertained by sitting in front of the TV or computer screen. We have taken to eating a bigger portion of food and also eating more junk food. We are tempted by the ‘up size’ offer when we order our food. We certainly have shunned physical activities and outdoor pursuits.

I am sure these SNPs linked to high BMI did not appear overnight. For all we know they could have been in the population before. Perhaps, over the last several decades, what we eat and what we do somehow triggered the SNPs to alter our body regulation of appetite or metabolism. Instead of waiting for a pharmaceutical company to come up with a new pill for obesity, would it not be more logical to watch what we eat and to exercise regularly in order to stave off the ever rising BMI? I for one would not be in favour of reaching for the pill!