Platinum Therapy

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Platinum Therapy is the use of platinum compounds, which are cell damaging agents, for the treatment of specific cancers, including testicular, ovarian, lung, bladder, and head and neck cancers. Platinum compounds produce changes in DNA structure, which causes cancer cell death (apoptosis). Platinum compounds currently used are cisplatin, carboplatin and oxaliplatin, either used alone or in combination with other chemotherapy drugs. Side effects of platinum therapy include general cell-damaging effects, such as nausea and vomiting, decreased blood cell and platelet production in the bone marrow (myelosuppresion) and decreased response to infection (immunosuppression). Specific side effects include kidney (nephrotoxicity) and nerve damage (neurotoxicity).
Platinum therapy is currently used in the treatment of various different cancer types. Platinum compounds cause apoptosis of cancer cells through changes in DNA structure, which inhibits DNA replication, transcription and cell division (the cell cycle). Cisplatin, carboplatin and oxaliplatin are platinum therapies currently used in Australia. These agents do not all have the same clinical efficacy in all cancer types.

Cisplatin

Cisplatin is currently used to treat testicular, ovarian, lung, bladder, and head and neck cancers. Although a successful treatment, it must been used with caution. Cisplatin is extremely nephrotoxic (damages kidneys) and requires increased water intake and excretion before, during and after therapy. This is the major factor affecting dose, and kidney function must be carefully monitored. Cisplatin is also associated with severe nausea and vomiting in almost all patients. This can often be prevented and treated by the use of medications, such as ondansetron. If nausea and vomiting cannot be controlled, cisplatin dose may need to be reduced or ceased completely. Cisplatin has a low level of myelotoxicity (bone marrow suppression), which is related to dose. Those on cisplatin therapy must also be monitored for low magnesium and low calcium levels in the blood, hearing problems, red and white cell levels, platelet function, liver function and neurological status. Tinnitus (ringing in the ears) and hearing loss in the high frequency range can occur, but these are usually transient and disappear after treatment has stopped. Peripheral and other nerve damage can occur, especially after prolonged treatment. Cisplatin treatment should be avoided if there is a history of allergy to cisplatin or platinum containing compounds, kidney, hearing disorders, bone marrow depression and those who are pregnant or lactating (Category D). It should also not be used in conjunction with other known nephrotoxic and ototoxic drugs (drugs that affect hearing), such as aminoglycoside antibiotics or loop diuretics.

Carboplatin

Carboplatin, a derivative of cisplatin, is mostly used in the treatment of advanced ovarian cancer. It can also be used in place of cisplatin to treat small cell lung cancer. It has not yet been shown whether carboplatin can be used in the treatment of bladder, cervical, endometrial, head and neck carcinomas. Carboplatin works in a similar way to cisplatin. However, its has slightly different side effects with less nephrotoxicity, neurotoxicity, ototoxicity, nausea and vomiting experienced by patients. Carboplatin is, however, more myelotoxic, which is the most common reason for decreasing dose. Other side effects include the liver damage, ototoxicity and electrolyte disturbances experienced with cisplatin. Hair loss occurs in 2% of patients. Carboplatin should be avoided in patients with pre-existing severe kidney problems, severe myelosuppression, those with a history of hypersensitivity and during pregnancy and lactation (Category D).

Oxaliplatin

Oxaliplatin belongs to a new class of platinum based compound and has been seen to be effective in various cancers that do not respond well to cisplatin. Its mechanism of action is not completely understood but it is believed to interact with DNA in a similar way to cisplatin and carboplatin. Oxaliplatin is used with other drugs in stage III (Duke’s criteria) colon cancer after complete removal of the primary cancer, and in the treatment of advanced colorectal cancer. Adverse effects are those of cisplatin and carboplatin, and also include pulmonary fibrosis (scar tissue in the lung’s connective tissue). Therapy should be stopped in the case of unexplained respiratory symptoms. Contraindications to use are those of cisplatin and carboplatin.

References

  1. Australian Medicines Handbook ONLINE (2005).
  2. eMIMS ONLINE (2005).
  3. Haslett, C et al (Editors) (2002), Davidson’s Principles and Practice of Medicine 19th Edition, Churchill Livingstone, London.
  4. Kumar, P and Clark, M Eds (2002), Clinical Medicine 5th Edition, W.B. Saunders, London.
  5. Virtual Cancer Centre’s Anatomy and Physiology – What is Cancer?.