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Back to Oncology Procedures

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 sulfonamides discovered by Domagk and penicillin G discovered by Alexander Fleming.

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).

Chemotherapy for cancer

Cancer is the uncontrolled growth of cells due to damage to DNA (mutations) and, occasionally, due to an inherited propensity to develop certain tumors.

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 generally chemotheraputic drugs 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 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, tumors 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 tumor cells are undergoing cell division at any time.

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

Types of drugs

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

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 cell tumors).

  • Alkylating agents

  • Anti-metabolites

  • Antitumor antibiotics

  • Plant 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. The main examples are vinca alkaloids such as vincristine.
     

  • Hormonal therapy

    A number of malignancies responds to hormonal therapy.

    • Steroids (often dexamethasone) can inhibit tumor growth or the associated edema (brain tumors.
    • 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.
    • Some other tumors are also hormone dependent, although the specific mechanism is still unclear.
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Treatment schemes

There are a number of strategies in the administration of chemotherapeutic drugs used today. Combined modality chemotherapy is the use of drugs with other cancer 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 minimizing 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 tumor 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 tumors are fast-dividing, and therefore very susceptible.

Delivery

Most chemotherapy is delivered intravenously. Depending on the patient, the cancer type, 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 and melphalan. Chemotherapy may be delivered through a central line, giving more reliable access to the circulatory system while preventing phlebitis in peripheral veins.

Side-effects

The treatment can be physically exhausting for the patient. Current chemotherapeutic techniques have a range of side effects mainly affecting the fast-dividing cells of the body. Important common side-effects include (dependent on the agent):

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

Virtually all chemotherapeutic regimens can cause depression of the immune system, often by paralysing the bone marrow and leading to a decrease of white blood cells, red blood cells and platelets. The latter two, when they occur, are improved with blood transfusion. Neutropenia (a decrease of the neutrophil granulocyte count below 0.5 x 109/litre) can be improved with synthetic G-CSF (granulocyte-colony stimulating factor, filgrastim, Neupogen?, Neulasta?) or GM-CSF.

In very severe myelosupression, 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 studies 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 increase the risk of cardio-vascular disease and occasionally leads to secondary cancer.

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