When the human genome was first sequenced in 2000, there was much fanfare surrounding this milestone in medical science. Soon after there was much excitement about how medical treatment for conditions such as cancer would be revolutionized. The buzz word was ‘personalized medicine’ because it would soon be possible to tailor treatment to each person depending on his / her genetic make up. We are not there yet with personalized treatment, but we can now offer molecular targeted therapy to cancer patients. However, does the mere basic gender difference affect our response to cancer treatment and the severity of side-effects experienced?

Non small cell lung cancer (NSCLC) is a leading cause of death for both men and women. Inoperable lung cancer is associated with a dismal prognosis even with conventional chemotherapy. It is well known that women with lung cancer live longer than men. However, no striking response differences to individual therapies have been seen between males and females until now with the use of targeted agents. These targeted agents worked by affecting the epidermal growth factor receptor (EGFR) and angiogenesis (formation of new blood vessels).

Smoking is the cause of lung cancers. However, lung cancer can occur in never-smokers as well. About 20% of lung cancer cases in women occur in never-smokers compared to 9% in men. Women are more likely than men to develop adenocarcinoma and small-cell carcinoma than squamous cell carcinoma. Unlike men, women who develop lung cancer are more likely to be younger (<50 years old), but have a lower mortality rate from non-smoking-associated lung cancer than men. The most obvious factor to account for the difference in susceptibility and outcome between men and women is most likely hormonal difference. A growing body of evidence points to the female hormone, oestrogen (or estrogen, American spelling).

Data analysis by the Southwest Oncology Group (SWOG) and the Eastern Cooperative Oncology Group (ECOG) has found that women with NSCLC survive longer than men. Thus the female gender confers a survival advantage. Women over 60 years old had longer survival times than younger women. This age-related survival difference was not seen in men. When measured, the estradiol levels in these women correlated with the outcome; a high level of estradiol is a marker of bad prognosis. Thus, within the female population, having too much oestrogen floating around is linked to poorer outcome. (Perhaps, having too little oestrogen, as in men, is also linked to poorer outcome.)

In the ECOG 1594 trial, the 4 chemotherapy regimens used for lung cancer did not show any difference in response or survival between the regimens. However, the mean survival time for women was 2 months longer when compared to men (9.2 vs 7.3 months). The women, compared to men, experienced increased drug toxicity such as alopecia, nausea and vomiting. In the E4599 trial, where the anti-angiogenesis agent, bevacizumab (Avastin), was added to conventional chemotherapy, the overall survival was improved from 10.3 to 12.3 months. However, the toxicity differences between men and women given bevacizumab as well were apparent. Women were more likely to develop significant hypertension (9.9% grade 3 / 4 in women vs 4.2% in men), constipation (5.3% grade 3 / 4 vs 1.4% in men) and grade 5 febrile neutropenia (2.4% vs 0% in men). The new agents targeting EGFR, such as gefitinib and erlotinib, have become part of the standard therapy for NSCLC. Two recent trials have shown that women had higher response rates than men to both gefitinib and erlotinib. The results of phase 3 studies on these new targeted agents in lung cancer are awaited with baited breath.

The day of truly personalized medicine has not dawned upon us. The hope that it will occur one day is a dream that keeps all researchers and clinician-scientists working feverishly on the genetic makeup of cancer. However, genes on the non-X / Y chromosome do not hold all the cards to this puzzle. No doubt the sex of a patient and the hormonal milieu will have a great influence on the incidence and outcome of a disease. (Another cancer where being female is an advantage is primary liver cancer or hepatocellular carcinoma.) Thus in the case of NSCLC, being female is indeed ‘king’.

Recently my daughter’s friend was diagnosed to be suffering from chronic fatigue syndrome (CFS). I remember her as a petite girl, freckled face and brimming with energy. Not long after returning to UK, she started to get tired easily. This fatigue feeling got worse with time. Eventually getting out of bed was a huge effort. After much investigation by the doctors, she was diagnosed to be suffering from CFS.

Chronic fatigue syndrome is also known as myalgic encephalomyelitis or myalgic encephalopathy (ME). CFS / ME is thought to affect at least 0.2 – 0.4 % of the population. Although many possible aetiologies (including infectious, endocrine, immunological, genetic, neurological and psychiatric causes) have been investigated, the exact aetiology for CFS / ME cannot yet be explained. So, is CFS / ME real? The answer is an unequivocal YES!

What are the symptoms of CFS / ME? As the name implies, the main symptom is fatigue. It is all encompassing fatigue and not your usual feeling of tiredness after a late night or a hard day at the gym. The characteristic symptoms of CFS include increased fatigue following exertion, difficulties with memory and concentration, muscle aches, joint pain (not associated with redness or swelling), problems with sleep, headache, sore throat and tender lymph nodes. On the Centers for Disease Control and Prevention (CDC) website, it was stated that these symptoms have to be present for 6 months or more before CFS can be diagnosed. To diagnosis CFS, it is a process of diagnosis by exclusion. As fatigue is a common symptom for lots of conditions, the doctor can only feel ‘confident’ about diagnosing CFS if he has excluded other conditions such as endocrine disorders, infectious diseases, cancer, orthopaedic problems and psychiatric problems. Although these patients usually do get a lot of blood tests and investigations done on them, the tests are not to diagnose CFS. They are used to exclude other conditions which might give rise to the symptoms of CFS / ME.

A study from Gloucester, UK looked at 811 general practitioners’ (GP) knowledge and attitudes on CFS (Fam Pract 2005 Aug 22 (4): 389 – 393). Although CFS as a clinical entity has been known for more than 2 decades, only 72 % of the GPs accepted CFS / ME as a clinical entity. When it came to diagnosis, only 52 % of them felt confident to diagnose CFS /ME. In 1996, three UK royal colleges agreed that CFS / ME existed as an independent diagnosis and treatments were possible. Unfortunately, there were few services available to help these patients until 2002 when the chief medical officer of UK endorsed an independent report which recommended the provision of services to help CFS / ME sufferers. Following this, funds for support services for CFS / MS were set up but only in England and not the whole country.

Perhaps more help will become available to CFS / ME suffers in UK with the recent publication of the guideline on CFS / ME by the National Institute for Health and Clinical Excellence (NICE). With this guideline on diagnosis and treatment, maybe more GPs will feel more confident in recognizing and diagnosing the condition. After all, the first step to recovery is acknowledging that your patient has a condition.