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Cisplatin Mechanism Of Action

Cisplatin Mechanism Of Action

Mechanism of Action

Cisplatin is believed to kill cancer cells by binding to DNA and interfering with its repair mechanism, eventually leading to cell death. The first step in the process (after the cisplatin molecule penetrates the cell membrane intact) is for a molecule of water to replace one of the chloride ions. The resulting structure can then bind to a single nitrogen on a DNA nucleotide. Then, the second chloride is replaced by another H2O and the platinum binds to a second nucleotide. Binding studies of cisplatin with DNA have indicated a preference for nitrogen 7 on two adjacent guanines on the same strand. It also binds to adenine and across strands to a lesser extent. The cisplatin-DNA complex attracts the attention of HMG (high mobility group)-1 and other DNA repair proteins which become irreversibly bound. The resulting distortion to the shape of the DNA prevents effective repair. (The trans isomer of cisplatin is unable to form 1,2 intrastrand links and lacks antineoplastic activity.) Other antineoplastic agents, such as etoposide, contribute to the platinum-DNA-protein complex and thus synergistically reinforce the activity of cisplatin.

Uses

Treatment of advanced bladder cancer, metastatic ovarian cancer, and metastatic testicular cancer. Testicular, ovarian, bladder, head and neck, esophageal, small and non-small cell lung, breast, cervical, stomach and prostate cancers. Also to treat Hodgkin's and non-Hodgkin's lymphomas, neuroblastoma, sarcomas, multiple myeloma, melanoma, and mesothelioma.

How to work?

Chemotherapy drugs that affect cells only when they are dividing are called cell-cycle specific. Chemotherapy drugs that affect cells when they are at rest are called cell-cycle non-specific. The scheduling of chemotherapy is set based on the type of cells, rate at which they divide, and the time at which a given drug is likely to be effective. This is why chemotherapy is typically given in cycles.

Dosages

For the treatment of bladder cancer.For the treatment of bladder cancer as a single agent.Intravenous dosage

Adults

50 to 70 mg/m2 IV as a single dose once every 3 to 4 weeks depending on the extent of prior exposure to radiation therapy and/or prior chemotherapy. An initial dose of 50 mg/m2 IV once every 4 weeks is recommended in heavily pretreated patients.

Side Effect

  • nausea and vomiting (may be severe),
  • diarrhea,
  • temporary hair loss,
  • loss in ability to taste food,
  • hiccups,
  • dry mouth,
  • dark urine,
  • decreased sweating,

Overdose

There is a very narrow range between the therapeutic dose and the minimum lethal dose. Dosage calculations need to be meticulously checked due to the toxicity of this drug.

Precaution

Your fertility, meaning your ability to conceive or father a child, may be affected by cisplatin. Please discuss this issue with your health care provider.Inform your health care professional if you are pregnant or may be pregnant prior to starting this treatment. Pregnancy category D (Cisplatin may be hazardous to the fetus. Women who are pregnant or become pregnant must be advised of the potential hazard to the fetus).For both men and women: Use contraceptives, and do not conceive a child (get pregnant) while taking cisplatin. Barrier methods of contraception, such as condoms, are recommended. Discuss with your doctor when you may safely become pregnant or conceive a child after therapy.Do not breast feed while taking cisplatin.

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