7(c): Chemotherapy
Briefing on this subject at the NSW Cancer Institute's day for patients and carers was given by Dr Helen Wheeler, leading neuro-oncologist. Dr Wheeler put the subject in broader context. This section reflects Dr Wheeler's briefing.
The neuro-oncology tasks are:
1. to develop better treatments
2. to understand the cause of brain tumour
3. to improve pathology testing so as
4. to be able to find treatments unique to the particular tumour
5. to make sure that treatments which work in the laboratory actually are able to reach their target; for example, Herceptin, a drug effective in cancer elsewhere, is a large molecule which does not get across the blood brain barrier
6. to be alert to, deal with drug interactions and aware of substances which may actually be 'antidotes' to chemotherapy
7. to be alert to side effects and
8. to make sure the person you are seeing right now gets the best treatment.
Since 2000, the Pharmaceutical Benefits Scheme (PBS) has covered Temodal, with better than other chemotherapy effects on malignant gliomas, fewer side effects.
Since 2005, the PBS has covered the 'Stupp Protocol' for malignant glioma. The elements of the Stupp Protocol are:
1. to remove the maximum amount of tumour by surgery
2. to provide six weeks of concurrent Temodal with radiotherapy
3. six months Temodal 5/28 (five consecutive days treatment each 28 days)
The Stupp Protocol was tested in an international clinical trial process: 573 volunteers, 18 months recruitment, three years follow-up, nearly five years therefore to obtain proof. The results were published in March 2005, the Federal Government gave support via the PBS from June 2005. This Australian approval was ahead of much of the world.
Why did it take so long to get the proof? The initial finding was that in fact the Stupp Protocol only provided a 50% chance of an extra 2.5 months of life in patients with GBMIV. However, after two years, twice as many patients were alive as otherwise... and after three years the number was four times as many as otherwise. Again, this is not a treatment which works for the majority, but for some, it works wonderfully well.
And on scans there is early evidence which suggests progression, now referred to as 'pseudo-progression'. This has led to erronious opinion in some treatment centres that a patient is worse; there is a need for proper management and understanding of results.
Dr Wheeler said that the big questions for the oncologist are these:
Why do some patients do well, while others do not?
If we can't find the difference, what do we do about it?
By way of response she ran through some current issues, as follows:
We are in a situation of change. Until the early 1990s only surgery, radiotherapy and very toxic chemotherapy. The story above outlines major change.
A grug called Taxol was very effective in the 1990s on other kinds of cancers, but not on BT patients ... Then it was realised that Dilantin and Tegretol and other antiseizure medications were metabolising the chemotherapy drugs before they had any effect. Results of older trials have to be discarded because they didn not take this into account. Some retesting with doses of five times those used previously is underway. This new understanding does not filter through the profession easily - for example, this knowledge about the effect of antiseizure medication
has not spilled over into treatment of other cancers of people with elipepsy. The knowledge needs to get to neurologists and specialists in other cancers.
There is an enzyme known as MGMT that comes along and repairs damage to glioma cells. You want not have mgmt around. Some tumours eliminate MGMT, but many questions still to be answered. Here is a fragment of research. The point is this: there are processes yet to be clearly understood which contribute to the variation in response to temozolomide or other drugs.
Dr Wheeler expressed concern about complementary therapies and their effect and the fact that patients may not confide to doctors what they are doing in this area. There is now evidence that vitamins to enhance the immune system can also enhance the defences of tumour cells. People are also, notably, using St Johns Wort for depression. However, this 'natural' substance is a powerful drug which potentiates the effect of antiseizure medications, thus impacting on the effect of chemotherapy... "I get the shudders because I do not know what my patients are doing." Dr Wheeler said.