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Perth Haematology :: Dr Steven Ward

Chemotherapy

 

Chemotherapy means chemical (drug) treatment. It is however usually reserved for drugs used to treat cancer.

 

There are many different drugs, and combinations of drugs, used in the treatment of many different cancers. Therefore do not rely on information or rumour that chemotherapy is horrid.

 

Chemotherapy generally works by killing cells which are actively growing and dividing.

Hence some of the side effects are  related to the fact that most chemotherapy is not specific for tumour cells, but will kill any cell in the process of dividing (into 2 daughter cells). This commonly affects the marrow cells, hair, and lining of the gut.

 

Chemotherapy drugs act on various stages of the cell cycle to prevent cell growth and differentiation.

 

The Cell Cycle

 

G1 = Gap 1: preparation for S phase

 

S = Synthesis : DNA synthesis, to make a second
exact copy of the DNA for the daughter cell

 

G2=Gap 2 : Preparation for M phase

 

M=Mitosis : the cell divides into 2 identical
daughter cells

 

G0 = a prolonged resting phase

(usually not sensitive to chemotherapy)

G1
G0
M
S
G2

 

 

 

 

DNA Damaging Drugs

The first chemotherapy drug developed (nitrogen mustard) in the 1940s is DNA damaging. Radiotherapy is also DNA damaging.

 

 

 

Examples of DNA damaging drugs:

Nitrogen mustards: Cyclophosphamide, Ifosfamide, Melphalan, Chlorambucil

Thiotepa, Mitomycin C

Busulfan

BCNU (carmustine)

Procarbazine, Dacarbazine, Tenozolomide

Platinum: Cisplatin, Carboplatin, Oxaliplatin

 

 

Anti-Microtubule Drugs

During cell division the microtubules provide support through which the chromosomes are segregated into the daughter cells.Damage to microtubles results in cell death.

 

 

Examples of Anti-Mocrtubule Drugs:

Vinca Alkaloids: Vincristine, Vinblastine, Vinorelbine

Taxanes: Taxol, Taxotere

 

Anti-metabolite Drugs

These drugs interfere with the normal cell metabolism. The usual target is DNA synthesis. Often these drugs mimic the normal substrate and leads to cessation of metabolism and cell death.

 

 

Examples of Anti-Metabolite Drugs

Methotrexate

5-Fluoruracil

Capecitabine

Purine analogs: Cladrabine, Fludarabine, Pentostatin

Gemcitabine

Cytarabine (Ara-C)

Mercaptopurine

 

Topoisomerase inhibitors

These drugs inhibit the Topoisomerase I or II enzymes responsible for maintaing DNA structure.

 

Examples:

Topo I Inhibitors: Irinotecan, Tpoptecan

Topo II Inhibitors:    Etoposide, Teniposide

Anthracyclines: Daunorubicin, Doxorubicin, Idarubicin, Epirubicin, Mitozantrone, Dactinomycin

 

 

 

New drugs are being developed to specifically target tumour cells or the altered cellular processes which lead to cancer, leading to cleaner drugs with fewer side-effects.

 

Examples:

Imatinib (Glivec): "Magic-bullet" designed to fit in the pocket of an enzyme and effectively prevent it from working, hence switching off the driver for DNA synthesis seen in CML. See CML section also.

Rituximab (MabThera): A monoclonal antibody directed at a marker on B-lymphocytes, leading to selective death of B-cells, without affecting other cells.

Thalidomide: An old drug, now used to treat Myeloma. Tis drug prevent angiogenesis (blood vessel prodcution) and so "starves" the tumour cells. Other actions are also likely.