Introduction

Cancer & Antineoplastics

Cancer can be defined very broadly as a disease in which there is uncontrolled manipulation and spread of abnormal forms of the body's own cells within in the body. It is one of the leading causes of death in the developed nations - one in five of the population of Europe and North America can expect to die of cancer ^¤. In the United States alone, approximately 400,000 people die from it each year ^¤. Figures for the last hundred years or so give the impression that the disease is increasing in these countries, however, we must not forget to consider the fact that cancer is largely a disease of the later age groups. With advances in public health and medical science, many more people live to the age where they are likely to get cancer.

There are three main approaches to dealing with established cancer - surgical incision, irradiation and chemotherapy - and the role of each of these depends on the type of tumour and the stage of its development. Chemotherapy with cytotoxic drugs is the main method of treatment for only a few cancers but it is increasingly used as an adjuvant to surgery or irradiation in a range of common types of tumour.

Cancer cells differ from normal cells in behaviour, in that they can manifest three characteristics not seen in normal cells ^¤:

Uncontrolled proliferation - Cancer cells multiply at a similar rate as normal cells such as bone marrow and epithelial cells. It is therefore, not generally true that cancer cells proliferate faster than normal cells, which is a common misconception. The significant difference however, is that of proliferation. Cancer cells grow without the restraints of normal feedback control mechanisms that regulate normal tissue or organ growth.
Invasiveness - During differentiation, and the growth of tissues and organs, normal cells develop certain spatial relationships with respect to each other. This spatial awareness is continuously maintained even when the cells are involved in repair processes. Cancer cells on the other hand, will not remain within a particular area of an organ, but instead, will grow extensively, invading the surrounding tissues.
Metastasis - When a tumour becomes metastatic, cells from the parent tumour are able to enter the bloodstream or lymphatic system. This allows for colonisation of new sites of the body, forming secondary tumours that reside elsewhere from the primary tumour ^¤.

Strictly speaking one should use the term "neoplasia" (new growth) rather than the term "cancer". Neoplasms that have only the characteristic of localised growth are classified as benign. Neoplasms with the characteristics of invasiveness and/or the capacity to metastasise are classified as malignant. The term "cancer" is usually applied only to this latter type of growth. The word "tumour", though defined as "a local swelling", is also often used interchangeably with "cancer" and will be so used here.

The cells of a solid tumour can be considered as belonging to one of three states ^¤:

Dividing state - Cancer cells are continuously in the cell cycle (constant growth and division);
Resting state - Cancer cells exist indefinitely in G0 and so have the potential to enter the cell cycle at any time and begin dividing;
Static state - Cancer cells are no longer able to divide, but contribute to the tumour volume.

Most antineoplastics, in particular those which are cytotoxic such as cisplatin, affect only the cancer cells in the dividing state which unfortunately, may form as little as 5% of some solid tumours. Although these drugs are said to be antiproliferative, they have no specific effect on evasiveness or the tendency to metastasise. Furthermore, they are indiscriminate, affecting all rapidly dividing normal tissues, and so are are likely to depress bone marrow and growth, impair hearing, cause sterility, hair loss, nausea and vomiting. An anticancer drug must therefore, be able to kill malignant tumour cells in vivo at doses that allow enough normal cells in the patient, to survive so that recovery can occur.

The term "cytotoxic drug" applies to any drug that can damage or kill cells. In practice, it is used more restrictively to mean drugs that inhibit cell division and are potentially useful in cancer chemotherapy. The main cytotoxic drugs can be divided into four general groups; alkylating agents; antimetabolites; natural products; and miscellaneous agents. We will be concentrating only on the sub-class of miscellaneous agents - the platinum compounds. Note that it is not unusual to classify these compounds as alkylating agents, as they act in a similar fashion. Of the platinum agents currently available today, cisplatin is the most potent and widely used. We will therefore, be looking specifically at this drug, discussing its mode of action, side effects, and other properties. The final page will end with the brief mention of some of the many cisplatin analogues that have since been developed.

Before such properties can be discussed, we should first take a brief look at its history to discover how such a simple metal complex has become to be known as one of the best selling cytotoxic chemotherapeutic agents in the world ^‡.

Last Modified on 24 June 1998

Introduction

Cancer & Antineoplastics

Copyright © 1998 Sai Man Liu