Chemotherapy

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. Antibiotics are referred to as antibacterial chemotherapy, but in medical practice this word is only used in the context of the treatment of tuberculosis.

Other uses of chemotherapy agents (including the ones mentioned below) are the treatment of autoimmune disease (DMARDs).

Table of contents

1 Chemotherapy for cancer 2 Types and dosage of drugs 2.1 Alkylating agents 2.2 Anti-metabolites 2.3 Plant alkaloids 2.4 Antitumour antibiotics 2.5 Hormonal therapy 3 Treatment schemes 4 Delivery 5 Side-effects 6 See also 7 References 8 External links

Chemotherapy for cancer

Broadly, most chemotherapeutic drugs work by impairing mitosis (cell division), effectively 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").

Unfortunately, scientists have yet to be able to locate specific features of malignant cells that would make them uniquely targetable (barring some recent examples, such as the Philadelphia chromosome as targeted by imatinib). This means that other fast dividing cells such those responsible for hair growth and replacement of epithelium in the intestine are also affected. However, some drugs have a better side-effect profile than others, enabling doctors to adjust treatment regimens to the advantage of patients in certain situations.

As chemotherapy affects cell division, tumours with a high growth fractions (such as acute myelogenous leukemia and the lymphomas, including Hodgkin's disease) are more sensitive to chemotherapy, as a larger proportion of the tumour cells are undergoing cell division at any time.

Chemotheraputic drugs affect "younger" tumours (i.e. less differentiated) more effectively, because at a higher grade of differentiation, the propensity to growth decreases. In some solid tumours, cell division has effectively ceased, making them insensitive to chemotherapy. Another problem with solid tumours is the fact that the chemotherapeutic agent often does not reach the core of the tumour. Solutions to this problem include brachytherapy and, of course, surgery.

Types and dosage of drugs

Some newer agents cannot be classified. This include the new tyrosine kinase inhibitor imatinib mesylate (Gleevec® or Glivec®), which directly targets a molecular abnormality in certain types of cancer (Chronic myelogenous leukemia, Gastrointestinal stromal tumors).

Dosage of chemotherapy can be difficult: if the dose is too low, it will be ineffective against the tumor, while at excessive doses the toxicity (side-effects, neutropenia) will be intolerable to the patient. This has led to the formation of detailed "dosing schemes" in most hospitals, which give guidance on the correct dose and adjustment in case of toxicity.

In most cases, the dose is adjusted for the patient's body surface area, a composite measure of weight and height that mathematically approximates the body volume. The BSA is usually calculated with a mathematical formula or a nomogram, rather than by direct measurement.

Alkylating agents

Anti-metabolites

Plant alkaloids

Antitumour antibiotics

Hormonal therapy

• Steroids (often dexamethasone) can inhibit tumour growth or the associated edema (brain tumorss).
• Prostate cancer is often sensitive to finasteride, an agent that blocks the peripheral conversion of testosterone to 5-hydroxy-testosterone.
• Breast cancer is often positive to the estrogen and/or progesterone receptor. Inhibiting the production (aromatase inhibitors)or action (tamoxifen) of these hormones can often be used as an adjunct to therapy.

Treatment schemes

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.

Most chemotherapy regimens require that the patient is capable to undergo the treatment. Performance status is often used as a measure to determine whether a patient can receive chemotherapy, or whether dose reduction is required.

Delivery

Side-effects

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

In very severe myelosuppression, which occurs in some regimens, almost all the bone marrow stem cells (cells which produce white and red blood cells) are destroyed, meaning allogenic or autogenic bone marrow cell transplants are necessary. (In autogenic BMTs, cells are removed from the patient before the treatment, multiplied and then re-injected afterwards; in allogenic BMTs the source is a donor.) However, some patients still develop diseases because of this interference with bone marrow.

Nausea and vomiting induced by chemotherapy can be alleviated with 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.

In particularly large tumors, such as large lymphomas, some patients develop tumor lysis syndrome from the rapid breakdown of malignant cells. Although profylaxis is available and is often initiated in patients with large tumors, this is a dangerous side-effect which can lead to death if left untreated.

Chemotherapy may increase the risk of cardio-vascular disease and occasionally leads to secondary cancer.

See also

• Cancer
• Gene therapy
• Experimental cancer treatments

1. MR Tramer 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

• Chemotherapy Regimens Database

Source | Copyright