Chemotherapy

Chemotherapy (pronounced keem-o-therapy) is the use of certain drugs to treat disease, as distinct from other forms of treatment, such as surgery. Chemotherapy dates at least as far back as the use, by the Indians of Peru, of cinchona bark in the treatment of fevers, such as malaria. The first modern chemotheraputic agent was Paul Ehrlich's arsphenamine, an arsenic compound discovered in 1909 and used to treat syphilis. This was later followed by penicillin.

Please note that today, the term chemotherapy is mostly used for the drug treatment of cancer, and the rest of this article discusses that topic.

Table of contents

1 Cancer chemotherapy 1.1 Types of drugs 1.2 Resistance 1.3 Administration 1.4 Delivery 1.5 Side-effects 1.6 Experimental techniques 1.7 References

Cancer chemotherapy

Mutations of normal cellss creates cancerous tumours which can grow out of control. Broadly, chemotheraputic drugs work by selectively targeting fast-dividing cells. As these drugs cause damage to cells they are termed cytotoxic. Some drugs cause cells to commit apoptosis (effectively cell suicide), but chemotheraputic drugs all block some essential feature of the cell division process which makes cells unable to divide.

Unfortunately, scientists have yet to be able to locate specific features of cancerous cells that would make them uniquely targetable. This means that other fast dividing cells such those responsible for hair growth are also affected. However by chance some drugs seem to affect cells from different tissues more intensely than others, and this can be used to the advantage of patients in certain situations.

Because the drugs target fast-dividing cells it is the tumours with high growth fractions which are more susceptible to being killed. Tumours such as those resulting from leukemia, lymphoma and Hodgkins disease are examples of these fast-dividing cells. The explanation is that drugs can only affect cancerous cells when they are at a certain stage in the cell cycle. As only a fraction of the cells are ever at this stage, the faster growing the tumour the more likely a high fraction of its cells are affected.

Chemotheraputic drugs affect younger tumours more effectively because as tumours get older their growth slows down. Some of the cells in solid tumours are not dividing at all, so no chemotheraputic drugs touch these. Drugs can often can not even penetrate the insides to work there.

Types of drugs

The majority of chemotheraputic drugs can be divided in to: alkylating agents, anti-metabolites, plant alkaloids, and antitumour agents. As all of the drugs affects DNA synthesis or function in some way, they are categorized by their effect on the cell cycle.

Alkylating agents
Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumour growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide.

Anti-metabolites
These substances masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division.

Plant (vinca) alkaloids
These alkaloids are derived from plants and block cell division by preventing microtubules being synthesized. These are vital for cell division and without them it can not occur.

Antitumour antibiotics
There are many differing antitumour antibiotics, but generally they prevent cell division by two ways: (1) binding to DNA making it unable to separate (2) inhibiting ribonucleic acid (RNA), preventing enzyme synthesis.

Steroid hormones
These act only on certain hormone-dependent cancers, although their specific mechanism is still unclear.

Resistance

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Administration

There are a number of strategies in the administration of chemotheraputic drugs used today. Combined modality chemotherapy is the use of drugs with other treatments, such as radiation therapy or surgery. Most cancers are now treated in this way. Combination chemotherapy is a similar practice which involves treating a patient with a number of different drugs simultaneously. The drugs differ in their mechanism and side effects. The biggest advantage is minimising the chances of resistance developing to any one agent. Adjuvant Chemotherapy can be used when there is little evidence of cancer present, but there is risk of recurrence. This can help reduce chances of resistance developing if the tumour does develop. It is also useful in killing any cancerous cells which have spread to other parts of the body. This is often effective as the newly growing tumours are fast-dividing, and therefore very susceptible.

Delivery

Most chemotherapy is delivered intravenously. Depending on the patient, the cancer, the stage of cancer, the type of chemotherapy, and the dosage, IV chemotherapy may be given on either an inpatient or outpatient basis. A few agents are given orally, such as prednisone. Chemotherapy may be delivered through a central line.

Side-effects

Current chemotheraputic techniques have a range of side effects mainly affecting the fast-dividing cells of the body. Important common side-effects include:

• hair loss
• vomiting and nausea
• anaemia
• depression of the immune system hence (potentially lethal) infections
• hemorrhage
• secondary neoplasms
• cardiotoxicity
• hepatotoxicity
• nephrotoxicity

The treatment can be exhausting physically for the patient. For some patients myelosupression occurs. In these cases almost all the bone marrow stem cells (cells which produce white and red blood cells for the rest of the body) are destroyed, meaning allogenic or autogenic bone marrow cell transplants are necessary (where cells are removed before the treatment, multiplied and then re-injected afterwards.) However, some patients still develop diseases because of this interference with bone marrow.

To alleviate vomiting and nausea induced by chemotherapy a group of auxiliary drugs is used. The drugs are called antiemetics. Usually metoclopramide or 5 hydroxytryptamine 3 (5-HT₃) receptor antagonists (dolasetron, granisetron, ondansetron) are used.

Some studies¹ and patient groups claim that the use of cannabinoids derived from marijuana during chemotherapy greatly reduces the associated nausea and vomiting, and enables the patient to eat.

Chemotherapy may cause an increased risk of cardio-vascular disease.

Experimental techniques

See also: Cancer -- Gene therapy -- Experimental cancer treatments -- insulin potentiation therapy

References

1. MR Tramèr et al. Cannabinoids for control of chemotherapy-induced nausea and vomiting: quantitative systematic review. BMJ 2001 323: 16-21. http://www.bmj.com/cgi/content/full/323/7303/16