Cisplatin

INTRODUCTION:
  • Cisplatin, cisplatinum, or cis-diamminedichloroplatinum(II) (CDDP) is a chemotherapy drug. 
  • It was the first member of a class of platinum-containing anti-cancer drugs.
  • Cisplatin is administered intravenously as short-term infusion in normal saline for treatment of solid malignancies.
INDICATIONS:
  • It is used to treat various types of cancers, including 
  1. Sarcomas, 
  2. Some carcinomas (e.g. small cell lung cancer, Oesophageaal CA, anal squamous cell carcinoma , and ovarian cancer), 
  3. Lymphomas, and 
  4. Germ cell tumors
  5. Thymoma
  6. Dysgerminoma
  7. Cisplatin is particularly effective against testicular cancer; the cure rate was improved from 10% to 85%
  8. In carcinoma cheek Cisplatin is the best drug for single drug chemotherapy 
MECHANISM OF ACTION:
  • Following administration, one of the chloride ligands is slowly displaced by water in a process termed aquation.
  • The aqua ligand in the resulting [PtCl(H2O)(NH3)2]+ is itself easily displaced, allowing the platinum atom to bind to bases.
  • Of the bases on DNA, guanine is preferred.
  • Subsequent to formation of [PtCl(guanine-DNA)(NH3)2]+, cross-linking can occur via displacement of the other chloride ligand, typically by another guanine.
  • The damaged DNA elicits DNA repair mechanisms, which in turn activate apoptosis when repair proves impossible.
  • DNA BINDING: Cisplatin binds to DNA and causes a critical structural change in the DNA – a bend of 45 degrees.
SIDE EFFECT:
  • Nephrotoxicity (kidney damage) is a major concern. 
  • Myelotoxicity: This agent can also cause profound bone marrow suppression.
  • Hemolytic anemia can be developed after several courses of cisplatin. It is suggested that an antibody reacting with a cisplatin-red-cell membrane is responsible for hemolysis.
  • Tacrolimus toxicity
  • Neurotoxicity (nerve damage) can be anticipated by performing nerve conduction studies before and after treatment.
  • Nausea and vomiting: cisplatin is one of the most emetogenic chemotherapy agents.
  • Ototoxicity (hearing loss): there is at present no effective treatment to prevent this side effect, which may be severe.
  • Electrolyte disturbance: Cisplatin can cause hypomagnesaemia, hypokalaemia and hypocalcaemia. The hypocalcaemia seems to occur in those with low serum magnesium secondary to cisplatin, so it is not primarily due to the Cisplatin
  • Secondary leukemia
Exam Question
  • Chemotherapy for dysgerminoma is Cisplatin, etoposide, bleomycin
  • Cisplatin is used in treatment of ovarian carcinoma
  • Nausea and vomiting: cisplatin is one of the most emetogenic chemotherapy agents.
  • Treatment of squamous cell carcinoma of anal canal is Cisplatin based chemotherapy followed by radical radiotherapy
  • Cisplatin is used in lung cancer is also used in ovarian carcinoma
  • Important chemotherapy agent used for the thymoma treatment is Cisplatin
  • Anti cancer drug causing nephrotoxicity is cisplatin
  • Cisplatin is associated with secondary leukemia
  • Cisplatin Causes tacrolimus toxicity
  • In oesophageal ca Cisplatin is used as a Neoadjuvant chemotherapy agent
  • Cisplatin is used in metastatic testicular carcinoma 
  • In carcinoma cheek Cisplatin is the best drug for single drug chemotherapy 
  • Predominantly sensory neuropathy is caused by Cisplatin

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