Chemotherapy

I

Introduction

Chemotherapy, literally, the treatment of a condition by chemical means; however, it is usually used with reference specifically to the treatment of cancer by the use of specific drugs which slow down the rate of growth of tumour cells. It is hoped that in the future chemotherapy will exploit some property unique to malignant tumour cells that is not shared with normal cells. However, no such property has been discovered to date and the drugs used in chemotherapy are usually cytotoxic (cell-killing) for all dividing cells, both malignant and normal. This non-specific effect gives rise to some of the unpleasant side effects of some chemotherapies. In the future, cancer cells may be more specifically targeted by linking the chemotherapeutic agents to monoclonal antibodies.

II

Use of Chemotherapy

Invasive cancer affects one third of people in Britain. One fifth dies from cancer. Management of the disease often involves close liaison between doctors, surgeons, and oncologists (tumour specialists). In treating cancer patients, surgery, radiotherapy (the use of radiation) and chemotherapy, immunotherapy, and gene therapy may be used either singly or in combination. In most cancer cases, treatment is aimed at improving the clinical state of the patient by reducing symptoms caused by the tumour. In some childhood cancers a cure is aimed at, but in adult cancer this is rarely achieved.

Many chemotherapeutic agents are now used and specific drug regimes exist for particular forms of cancer. The majority of the chemotherapeutic agents currently available interfere with one or more cellular processes involved in cell division (mitosis), including the movement of chromosomes during cell division. Because the process of cell division is common to both normal and malignant cells, chemotherapeutic drugs cannot in themselves be specific in their actions. Fortunately, normal cells from different tissues differ in their susceptibility to different drugs; the reasons for this are largely unknown.

After treatment with chemotherapeutic drugs, normal cells appear to have a greater ability to regenerate (regrow) and to repopulate the tissues. This selective regrowth advantage appears to allow normal cells to repopulate a diseased tissue more preferentially than tumour cells. However, one can never be sure whether all the tumour cells have been destroyed. If they have not, recurrence of the tumour at that site is most likely to occur; however, this is not defined solely by the number of surviving tumour cells, but also by the ability of the immune system to remove tumour cells.

III

Alkylating Agents

There are several types of chemotherapeutic drugs now available for the treatment of malignancies. The first of these are the alkylating agents. These are synthetic compounds of considerable chemical diversity that have the common ability to add alkyl groups to a wide range of electronegative groups under mild aqueous conditions that prevail in the living cell, be it cancerous or normal.

Their action is believed to occur by the cross-linking of guanine molecules (parts of the building blocks of deoxyribonucleic acid (DNA—see Nucleic Acids)) on adjacent strands of DNA, thus mechanically inhibiting the uncoiling of DNA necessary for DNA replication and cell division. Examples of these agents are chlorambucil, melphalan, and mustine. In clinical practice they are used to treat Hodgkin's disease (a lymphoma—malignancy of lymphoid tissue) and other types of lymphoma; chronic lymphocytic leukaemia; multiple myeloma (tumour of plasma cells); and occasionally for the treatment of seminoma (tumour of the testis); ovarian carcinoma; breast carcinoma; neuroblastoma (a tumour of primitive nerve cells common in childhood); and some sarcomas (tumour of soft tissue, such as skeletal muscle, fat, and bone).

IV

Antimetabolites

The second group are the antimetabolites, which are synthetically prepared copies of naturally occurring substances that play an essential role in the metabolism of normally proliferating cells. Many of these types of drugs interfere with the production of purine and pyrimidine bases (building blocks of DNA) or their incorporation into the DNA chain. Examples of these types of chemotherapeutic drugs are folic acid antagonists. Their clinical uses include the treatment of lymphoblastic leukaemia, Burkitt's lymphoma (a type of lymphoma common in children in Africa), and other lymphomas. Occasionally these drugs are also useful in the treatment of head and neck cancers.