Chemotherapy

Overview:

• IV administration of anticancer agents enables therapy to potentially reach metastatic disease in any part of the body
• However, the toxicity of chemotherapy determines that the drugs can only be given intermittently and that time has to be allowed for normal tissues to recover between each administration of new cytotoxic drugs
• It is also known that tumours rapidly develop resistance to single agents given on their own
• For this reason, the principle of intermittent combination chemotherapy has developed:
• Several drugs are combined together
• Chosen on the basis of their differing mechanisms of action and non-overlapping toxicities

• It has become apparent that normal tissue repairs much more rapidly than cancerous tissue. This makes it possible to continually deplete the tumour whilst allowing the restoration of normal tissues between chemotherapy cycles

Side-effects of chemotherapeutic drugs:

• Nausea and vomiting
• Hair loss
• Bone marrow suppression
• Cardiotoxicity
• Neurotoxicity
• Nephrotoxicity
• Sterility
• Secondary malignancies

Drug resistance:

• This is one of the major obstacles to curing cancer with chemotherapy
• Some tumours have an intolerably low-level of resistance to currently available treatment and are often cured:
• Testicular teratomas
• HD
• Childhood acute leukaemia

• Solid tumours (such as small-cell lung cancer) initially appear to be chemosensitive, with the majority of patients responding, but most patients eventually relapse with resistant disease
• In other tumours (e.g. melanoma) the disease is largely chemoresistant from the start

Adjuvant therapy:

• When a patient first presents with a tumour, it is possible that small amounts of tumour tissue have already spread to the lungs, liver, bone marrow and other sites
• This micrometastatic disease consists of relatively few cells with a good blood supply and might be particularly amenable to the action of anticancer drugs
• Therefore, if the primary tumour is removed and the tumour has a great likelihood of relapse, chemotherapy can be given to destroy the residual micrometastatic disease
• Adjuvant therapy is very useful in childhood cancers
• In adults, adjuvant therapy has been shown to be of use in breast and colon cancer