Sunday August 17, 2008
Understanding cancer treatment
LIVING WITH CANCER: By Dr Saw Min Hong
This is the first in a two-part series on understanding cancer treatment.
SOMEHOW it will not be easy to discuss the issue of chemotherapy in a neutral, emotionless and objective way, especially for those who had seen the performance of Jack Nicholson and Morgan Freeman in the The Bucket List.
It elicits mixed feelings, sometimes poignant, in many who are presently undergoing the treatment; or those who had gone through the experience and are now well; or those who had lost their loved ones either because chemotherapy was not able to control or cure the cancer illness.
To add to the difficulties, there seems to be a perceptible gap between the medical profession involved in the work of cancer treatment and the understanding of the public.
It would be good if at the end of this, chemotherapy can be accepted with a rational expectation that does not overpromise.
The disease called cancer
In cancer illness, a lump of cells have transformed to a state where the dividing cells no longer follow the physiological needs of the body. It has attained self “autonomy” and no longer responds to the cell cycle check and balance.
The continuing enlargement of this lump of cells disrupts the workings of the normal cell structure and damages the function of the organs involved.
In addition, these cells are capable of migrating by transporting through the blood circulation and through the lymphatic system to other parts of the body. This is known as metastases.
The metastatic colonies go on to interfere adversely on the workings of other organs, and further affects the health of the patient.
Chemotherapy is a class of drugs that are designed to cause cell death. The main indication in medical practice is to kill off cancer cells that have become harmful and threatening to the life of that individual.
Advances in treatment
It is easy to take for granted and to forget that many of the cancer illnesses are practically incurable as recent as 40 years ago, and it could be a lot more recent than that in this country.
Paediatric textbooks in the late 70s still regarded childhood “Acute Lymphoblastic Leukaemia” (a fast growing form of cancer of the white blood cells), as an unfortunate malignant illness and best dealt with in a palliative approach.
Presently, up to 80% of these children are cured of their disease if they fall under the good risk group.
Other examples include Non-Hodgkin’s Lymphoma (a type of cancer of the lymphatic system) where up to 40% of cases in the early stages can be cured. Patients who are less than 60 years old with certain types of leukaemia can look towards a 30-40% cure rate.
Many patients with Germ Cell Tumour (a type of cancer that develops from germ cell, a type of cell that matures into eggs in the ovaries or sperm in the testes) are given a second chance to get on with their life. The famous cyclist with a similar cancer illness had gone on to win the Tour De France.
All these advances would not have been possible if the pioneering oncologists that first adopted and saw the potential of chemotherapy were thwarted and inhibited by the worries of chemotherapy-induced side effects.
Needless to say, we are not seeing an ideal modality of treatment here. Many still failed after completing chemotherapy, and many of the side effects are not exactly a stroll in the park.
Having said that, this usually depends on how much of medical progress has come about – in a steady, cumulative improvement, punctuated by a greater paradigm shift that established the next benchmark.
While all these are happening, another important aspect of medical treatment with chemotherapy is the improvement in mitigating the many side effects directly or indirectly caused by it.
This involves reducing the mortality and the morbidity caused by treatment and improving the odds of curing certain cancer illness. With the gathering of more confidence, the dose of the chemotherapy treatment is often escalated to find the optimum dose.
In addition, further experiments were also done by combining different chemotherapeutic agents to find the best synergistic pairing. This type of progress has transformed the cure rate of many types of cancer illness.
Indiscriminate cell killing
This is the quote frequently mentioned by the non-protagonist of chemotherapy. It is true that chemotherapy works by killing dividing cells, and this includes the cancer cells, the hair follicles, the cells lining the gastrointestinal tract, and some cells in the bone marrow.
This would result in hair loss, mouth ulcers, mouth inflammation, diarrhoea, and low blood count that sometimes result in febrile illness and bleeding complications. The stakes are high, and would be better managed by trained staff.
Having said that, the hair does grow back after treatment, and the marrow cells normalise on completion of the chemotherapy treatment. The mouth ulcer will heal, and the diarrhoea will stop with appropriate treatment. All these are reversible. The tissues will recuperate, the damage rarely permanent.
More important is the fact that although the number of cancer cells is high, it is still a small percentage of the total number of cells the body has.
The number of cells killed in the lump of malignant tumour is at a much larger proportion than in the normal organs. So the killing may be indiscriminate but the cancer is affected more.
The better treatment is obviously a drug that is able to discriminate the cancer from non-cancerous cells. A drug that is able to leave the normal cells untouched and unharmed, and attacks only the cancer cells.
That moment will arrive once science is able to exploit the biological differences between the cancer and the normal cells. However things are not that simple, since the cellular environment of cancer cells is not that hugely different from normal cells.
Without any doubt, the field will continue to improve, new drug molecules will continue to be refined, a better response rate can be expected, but these require continuing research and time.
The immune system and risks of infections
It is true that patients receiving chemotherapy are more vulnerable to infection than normal people. However the extent of this susceptibility is often predictable and can be avoided in many cases. The risk of infection with most chemotherapy treatment is usually less than 20%, except in two situations.
The immune system is a highly complex but well organised system. It consists of two different classes of cells. The first component is adaptive, and this is made up of “trained” lymphocytic cells (a type of white blood cell) that have the intelligence to recognise self from non-self tissue. They remember infective agents the body has previously encountered.
This constitute the very important immune response that will reduce the severity of the same infection if it were to happen the second time. This is also the immune system that can be prepared through vaccination to protect the body against a particular infective agent.
The second component is less discriminative and is made up of non-adaptive “granulocytes”, another type of white blood cell. Although more primitive in its making and less sophisticated, it is equally as important. These cells often are the quick response first-line soldiers that will mop up any bacteria that seeped through the various portals, either from the intestinal tract, respiratory tract or the urogenital tract.
Chemotherapy hardly affects the first component of the immune system. However, it affects mostly the granulocytes in the second component of the immune system, reducing its numbers temporarily, but reversibly. The reduced absolute count correlates directly to the risk of infection.
The absolute number of granulocytes, together with the length of time that the granulocytes remain below certain critical values, often determines whether infection will occur or not.
This predictable correlation offers the opportunity for the oncologist to mitigate the risk of infection by pre-emptively using “granulocyte growth factors”, with the aim of stimulating the bone marrow to boost the production of the granulocytes, keeping the absolute counts up and shorten the duration where the counts are low.
The availability of this option has facilitated the practice of cancer treatment, and reduced related morbidity and the mortality.
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