CANCER AND CHEMOTHERAPY
If members of the public are asked to name the class of drugs most associated with cancer treatment, they will say chemotherapy. The term covers a wide range of different agents with diverse origins from antibiotics to plant extracts to synthetic chemicals based on DNA. All interfere with the mechanics of cell division and, as many tissues have dividing cells, this leads to the typical side effects such as nausea and vomiting (partly from damage to the gut lining, partly from a direct effect on the brain), hair loss (damage to hair follicles), and risk of infection (damage to the production of white blood cells needed to defend against infection). We are all familiar with the images of billiard-ball bald patients ‘fighting’ cancer (to use the tabloid press term). Whilst this does occur with chemotherapy, the reality is more varied, with much chemotherapy given in the outpatient setting producing little nausea or hair loss. Hair loss is hard to prevent, but it is not a uniform property of all chemotherapy drugs. Nausea and vomiting are now pretty largely preventable, allowing the administration of drugs hitherto considered too toxic, even to quite elderly patients. This is important because much chemotherapy is given for palliation of symptoms; hence quality of life is of paramount importance. There is arguably little point to life prolongation if the quality of that life is poor.
The first chemotherapy drugs were based on chemicals derived from mustard gas, used extensively to ghastly effect in the First World War. It was noted that soldiers exposed to these agents who survived would experience drops in their white blood cells (the cells in the blood that are responsible for defence against infection). There is, of course, a cancer of the white blood cells – usually termed leukaemia. Trials were carried out of mustard gas derivatives such as mustine in both leukaemia and a second related group of cancers called lymphoma. Patients in these trials experienced for the first time remissions of what had previously been untreatable conditions. With drugs used singly, unfortunately these remissions turned out to be temporary. However, further drugs followed, and trials established that using these drugs in combinations could lead to cures for patients with leukaemia and lymphoma.
A wave of new chemotherapy drugs followed, and in the 1970s and 1980s it was widely assumed that these would in turn lead to curative therapies for most cases of advanced cancer. These drugs came from a variety of sources. Plant extracts (vincristine, docetaxel, paclitaxel), complexed heavy metals (cisplatinum, carboplatin), and antibiotics (doxorubicin, mitomycin) proved to be fruitful areas of discovery leading to large-scale laboratory screening programmes looking for promising chemicals in a whole range of plant and bacterial extracts. Another area of discovery was compounds derived from the components of DNA or other building blocks of the cell division process, the best example being 5-fluoro-uracil, which is a derivative of uracil, one of the components of RNA. The extra fluorine atom in the molecule allows 5FU to interact with DNA and RNA but not to be processed normally – a molecular ‘spanner’ in the works.