Chemotherapy Drug Side Effects - Cancer Chemotherapy Treatment

Chemotherapy employs systemically administered drugs that directly damage cellular DNA (and RNA). It kills cells by promoting apoptosis and sometimes frank necrosis. There is a narrow therapeutic window between effective treatment of the cancer and normal tissue toxicity, because the drugs are not cancer specific (unlike some of the biological agents), and the increased proliferation in cancers is not much greater than in normal tissues. The dose and schedule of the chemotherapy is limited by the normal tissue tolerance, especially in those more proliferative tissues of the bone marrow and gastrointestinal tract mucosa. All tissues can be affected, however, depending upon the pharmacokinetics of the drug and affinity for particular tissues (e.g. heavy metal compounds for kidneys and nerves).

The therapeutic effect on the cancer is achieved by a variety of mechanisms which seek to exploit differences between normal and transformed cells. While most of the drugs have been derived in the past by empirical testing of many different compounds, e.g. alkylating agents, the new molecular biology is leading to renewed attempts to target particular genetic defects in the cancer.

Toxicity to normal tissue can be limited in some instances by supplying growth factors such as granulocyte colony-stimulating factor (G-CSF) or by the infusion of stem cell preparations to diminish myelotoxicity. The use of more specific biological agents with relatively weak pro-apoptotic effects in combination with the general cytotoxics may also improve the therapeutic ratio.

Most tumours rapidly develop resistance to single agents given on their own. For this reason the principle of intermittent combination chemotherapy was developed. Several drugs are combined together, chosen on the basis of differing mechanisms of action and non-overlapping toxicities. These drugs are given over a period of a few days followed by a rest of a few weeks, during which time the normal tissues have the opportunity for regrowth. If the normal tissues are more proficient at DNA repair than the cancer cells, it may be possible to deplete the tumour while allowing the restoration of normal tissues between chemotherapy cycles.

In many experimental tumours it has been shown that there is a log-linear relationship between drug dose and number of cancer cells killed and that the maximum effective dose is very close to the maximum tolerated dose at which dose-limiting toxicity is reached. With a chemosensitive tumour, relatively small increases in dose may have a large effect on tumour cell kill. It is therefore apparent that where cure is a realistic option the dose administered is critical and may need to be maintained despite toxicity. In situations where cure is not a realistic possibility and palliation is the aim, a sufficient dose to exceed the therapeutic threshold, but not cause undue toxicity, is required as the short-term quality of life becomes a more important consideration.

Side-effects of chemotherapy

Chemotherapy carries many potentially serious side-effects and should be used only by trained practitioners. The four most common side-effects are

vomiting,

hair loss,

tiredness and

myelosuppression.

Side-effects are much more directly dose related than anticancer effects and it has been the practice to give drugs at doses close to their maximum tolerated dose, although this is not always necessary to achieve their maximum anticancer effect.

However, there are problems. Not all cancers are any more responsive to high doses of chemotherapy than they are to conventional doses. Second, it may not be possible to collect haemopoietic progenitor cells from some patients, and those cells which are collected may be contaminated with tumour cells and lead to relapse of the primary malignancy. Third, even rescue with haemopoietic progenitor cells results in a period of severe cytopenia lasting around 2 weeks, with associated morbidity. Fourth, there is a long period of immunosuppression for 6-12 months following the transplant, resulting in an increased risk of life-threatening opportunistic infections. Nevertheless, the procedure remains effective treatment for many patients with haematological malignancies, and clinical trials in other tumours continue.

Recently, it has been possible to engraft a donor immune system to achieve an anticancer effect with lesser doses of chemotherapy, in a procedure known as a 'non-myeloablative transplant' for previously untreatable cancers. Conventional and non-myeloablative procedures are complicated by the toxicity of 'graft-versus-host disease', an immune reaction of the donor cells against normal host organs, which can affect 30-50% of transplant recipients and is potentially fatal in some cases. Immunosuppression, both from conditioning therapy and from the immunosuppressive drugs given to prevent graft-versus-host disease, results in a high incidence of opportunistic infections. Mortality therefore from allogeneic stem cell transplantation is a major problem, with 20-40% at risk of dying from the procedure, depending on the age and status of the recipient, and the degree of HLA compatibility of the donor (see also Immunotherapy).

Cancer Tip

Remember you are receiving drugs (chemo-therapy) already. Alcohol and other drugs mayinterfere with the treatment(s) you are receiving.Your kidneys and liver are already working extrahard to deal with chemotherapy. Don’t over-stress them with more drugs.

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Health Tip

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