The Penicillin of Cancer

Side Effects of Cisplatin

Cisplatin has quite a few side effects. The type and severity of effects vary considerably from patient to patient. Sometimes they are tolerable. For some these side effects are made worse by other medications or comorbid conditions.

Cisplatin's widespread use is due to it effectiveness, so the benefits outweigh the detractions much of the time. Also, since cisplatin has well-known and widely documented effects and side-effects, it can be used as a base treatment to provide consistent care for the patient while testing the effectiveness and side effects of another drug.

Some side effects of cisplatin:

  • Changes in how food tastes
  • Diarrhea
  • Nephrotoxicity - causes damage to the kidneys
  • Neurotoxicity - causes damage to the nerves
  • Nausea and vomiting
  • Ototoxicity - hearing loss. Scary because this is not treatable
  • Alopecia - hair loss
  • Decrease of blood cell production in the bone marrow, which is related to:
    • Thrombocytopenia (low blood platelet count)
    • Leucopenia (low white blood cell count)
    • Myelosuppression (decrease in bone marrow effectiveness)
    • Numbness in the extremities
    • Extreme fatigue

A large number of adjuvants have been tried to limit the toxicity of cisplatin. A review of therapies to prevent neuropathy - therapies that include glutathione, acetylcysteine, and vitamin E - found no real evidence that anything did any good.

The side effects are generally reversible and subside when treatment ends. However, renal toxicity is cumulative, and can result in complications months after treatment ends. Myelosuppression also accumulates over the course of the treatment, but it subsides with the end of treatment.

Since alkylating agents are designed and intended to destroy human cells (tumors are, after all, collections of abnormal human cells of a particular type), inevitably non-cancerous cells will be destroyed as well. The most common toxicities (side-effects) that occur as a consequence of alkylating agent treatment are related to the destruction of normal cells.

Alkylating agents are known to cause a dose-dependent destruction of certain cells of the immune system. In the treatment of autoimmune diseases, this is occasionally an advantage (such as with cyclophosphamide), but in cancer treatment it can cause severe immunosuppression. This state makes cancer patients treated with these drugs particularly susceptible to certain infections, including infections by microorganisms that do not often infect people with a normal immune system (e.g. fungi). Another common side-effect related to cellular destruction affects rapidly dividing cells, such as mucosal cells. This becomes clinically apparent in damage done to the oral mucosa and to the lining of the gastrointestinal tract—bleeding gums and copious, sometimes bloody diarrhea can occur. Poor absorption of nutrients across the GI tract can take place as well.

Peripheral neuropathy is a common side effect of cisplatin. The drug alters the amplitude of action potential on sensory nerves, as well as conduction velocity through the nerve fibers. Scientists found cisplatin activates "ion channels on dorsal root ganglia and dorsal horn neurons."

A Way Around the Side Effects?

Researchers are trying to develop platinum-based chemotherapy agents without as severe side effects as the ones currently on the market. The idea is that rather than using molecules in the cis configuration such as cisplatin and carboplatin, to put the ligands on in trans configuration. Read about it here.

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