CANCER CHEMOTHERAPY NOTABLE SUCCESS
In the 1970s and 1980s, further notable successes followed; in particular advanced testicular cancer was transformed from a lethal to a highly curable condition. The magnitude of this success is best illustrated by seven-time Tour de France champion Lance Armstrong who was diagnosed with a very extensive disease, including brain involvement. After successful extensive chemotherapy, he went on to win his first Tour, followed by a record-breaking six further triumphs. Similar successes have been seen in the leukaemias and a range of childhood cancers. Sadly, however, the major cancer killers have proved to be more resistant to chemotherapy, with cures elusive, although most tumour types will respond to chemotherapy to a degree. It was suggested that the problem may have been that insufficiently large doses of chemotherapy were being given. However, a round of trials in the 1990s showed that even extreme doses of combination chemotherapy together with a bone marrow transplant were unable to cure major killers such as advanced breast cancer.
This realization has led to a change of emphasis. The observation that advanced disease, while incurable, would respond to chemotherapy for a while led to the testing of chemotherapy in the setting of early disease, as had previously been done with hormone therapy. It was known that many patients with no obvious disease nonetheless later developed recurrence. This suggested that there must be very small amounts of cancer lurking undetected. The hypothesis was that giving chemotherapy early may work better than waiting for detectable relapse. Initial trials were disappointing but with hindsight were simply too small to detect the benefits. When trial results were pooled in breast cancer, it was realized that there was a benefit to early chemotherapy, with women receiving it relapsing later and surviving longer compared to those for whom chemotherapy was saved as a ‘salvage’ treatment. This is called adjuvant therapy and works on the principle that so-called ‘micro-metastatic’ disease may be eradicable, whereas once the disease is visible on a scan it is incurable. Essentially, modern scanners, whilst very sensitive, are unable to detect tumours smaller than a few millimetres across. Hence we cannot distinguish between people who have been cured by initial surgery or radiotherapy and those who have apparently normal scans but in reality harbour small residual tumour deposits destined to cause relapse in the future. Subsequent studies have refined the drug combinations used and also the groups of women deriving most benefit. The problem with adjuvant therapy is that many women will do well just with surgery and radiotherapy, and thus derive no benefit from the chemotherapy, only toxicity and potential harm. This risk is greatest for those with lowest risk of disease recurrence, either due to less aggressive disease or high risk of death from other causes (for example, the very elderly).
More recently, greater emphasis has been placed on the role of chemotherapy in palliation of symptoms. This may seem like an oxymoron – giving toxic drugs to reduce suffering. However, improved symptom control, in particular with drugs that prevent severe nausea previously associated with chemotherapy, and has transformed the value of these agents for palliation. The survival gains seen are often relatively modest – typically a matter of months – leading to researchers developing methods for measuring the quality of life. This allows comparison of toxic drugs producing benefit, for example by reducing pain, with alternatives often described under the blanket term of ‘best supportive care’ – painkillers, radiotherapy, and so on.
These two trends – adjuvant and palliative use – have greatly increased the cancer drug bill in the developed world as, although the gains are relatively small, the numbers who can benefit are enormous, and this has resulted in widespread use of chemotherapy in relatively elderly cancer patients.