Chemotherapy

Different drugs are used for treating lung cancers. Just like weed killers kill weeds and not the grass, or antibiotics kill bacteria and not us, the chemotherapy drugs are aimed at attacking rapidly dividing cells as are present in cancers and not normal body cells.

All cells in the body undergo a cell cycle of division as described in the drawing. Resting cells in the G0 phase divide by mitosis through a sequence of events and the resulting cells once again go into the resting phase.

Chemotherapy involves giving drugs which kill the cancer cells by attacking the dividing cells at different stages of the cell cycle.

Drugs commonly used are:

• Cisplatinum
• Etoposide
• Carboplatin
• Gemcitabine - Gemzar
• Paclitaxol - Taxol
• Methotrexate
• Docetaxol-Taxotere

Adverse Effects of the Chemotherapy:

• Blood cells - Low blood cell counts, from bone marrow suppression.
• The mouth - ulcers in the mouth
• Nausea and vomiting and loss of appetite
• Diarrhoea and constipation
• Hair loss
• Reproductive effects.
• Other effects.
• Numbness and tingling in the fingers or toes.

The effects of chemotherapy vary with the doses used and the combinations used. If given with radiation to the chest, chemotherapy may be given on week 1 and week 5 of, for example, a 6 week course of radiation treatment. If one likens chemotherapy to a weed killer that kills weeds and not the grass, one can understand that sometimes the grass ( normal body cells ) is affected by the weed killer being sprayed all over the area. Given time most of this effect corrects itself. On occasions a drug to stimulate bone marrow (Gm CSF - granulocyte, monocyte, colony stimulating factor) is used, but not all the time.

Chemotherapy effectiveness can be affected by several mechanisms:

1. Large tumour volume
2. The prescence of non dividing cells in the tumour
3. Cancer cells with different apoptotic pathways (differeng ways of cell death)
4. Presence of drug resistant tumour cells.

The chemotherapy drugs have a variety of targets, however they cause disruption in some normal cellular processes which are so dramatic that the cell must either repair itself quickly or initiate its own destruction (apoptosis). In apoptosis the cell shrinks and condenses, fragmenting into multiple membrane-bound bodies which are engulfed by surrounding cells without inflammation or damage to the surrounding tissues. At a biochemical level apoptosis involves fragmentation of nuclear DNA.

General Principles of Chemotherapy:

Aims of treatment must be clearly discussed from the beginning as to whether the lung cancer can be cured or can only be palliated (ie. growth temporarily halted). Combinations of drugs are usually employed and multiple cycles are used to kill as many cells as possible. without life threatening toxicity or development of resistance.

Age is not necessarily a factor in whether to treat or not, but rather age related organ dysfunction such as bone marrow reserve and renal function may increase risks of toxicity.

The performance status usually correlates with the response (ie. if a patient is quite fit despite the cancer, then the results are better). If patients are malnourished with low serum proteins, the binding of some drugs is affected adversley. Drug doses are adjusted for actual and predicted body weight, cardiac function, liver function and blood counts.

It is common to evaluate patients after 2 or 3 cycles of treatment to determine the treatment effectiveness. If a response is seen, then therapy is usually given for several cycles beyond that for the complete response. If tumour progression is noted, therapy is not continued. For patients with stable disease,an assessment of drug toxicity is important. If therapy is tolerable, a decision to continue treatment is reasonable with the understanding that eventual disease progression will occur.