Cisplatin
Cisplatin , cisplatinum or cis-diamminedichloroplatinum(II) (CDDP) is a platinum-based chemotherapy drug used to treat various types of cancers , including sarcomas, some carcinomas (e.g. small cell lung cancer, and ovarian cancer), lymphomas and germ cell tumors. It was the first member of its class, which now also includes carboplatin and oxaliplatin.
Mechanism of effect
Alkylating agents work by three different mechanisms:
1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA.
2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription.
3) the induction of mispairing of the nucleotides leading to mutations.
Pharmacodynamic
Cisplatin is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells.
They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide.
In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.
Pharmacokinetics
• Half-life elimination (terminal): 24hr to 47 days
• Protein bound: >90%
• Excretion: Urine (90%); feces (10%)
• Clearance: 15 L/hr/m²
• Vd: 11 L/m²
Dosage
• Metastatic Testicular Tumors
- Usual dose in combination with other approved chemotherapeutic agents is 20 mg/m²/day IV for 5 days/cycle
- Pretreatment hydration: 1-2 L fluid infused for 8-12 hr before dose
- May use concomitant amifostine to decrease nephrotoxicity
- Do not repeat course until SCr <1.5 mg/dL [<133 micromoles/L] or BUN <25 mg/dL [<8.93 mmol/L] or WBC >4000/mm³ AND platelets >100 k/mm³
• Advanced Bladder Cancer
- 50-70 mg/m² IV cycle q3-4Weeks, depending on prior radiation therapy or chemotherapy; for heavily pretreated patients, give 50 mg/m²/cycle initially; repeat q4Weeks
- Pretreatment hydration: 1-2 L fluid infused for 8-12 hr before dose
• Metastatic Ovarian Carcinoma
- 75-100 mg/m² IV per cycle q4Weeks with cyclophosphamide (600 mg/m² IV q4Weeks); administer sequentially
- Off-label: 90-270 mg/m² intraperitoneal; retain for 4 hr before draining; repeat q3Weeks (may coadminister systemic Na thiosulfate)
- Pretreatment hydration: 1-2 L fluid infused for 8-12 hr before dose
• Cancers (Off-label)
Cancer of cervix, endometrium, prostate, esophagus, kidney; non-small cell lung cancer; head & neck squamous cell cancer; osteogenic sarcomas; bone marrow transplants
- 75-100 mg/m² IV q4Weeks when used with cyclophosphamide
- 100 mg/m² IV q4Weeks as single agent
- Pretreatment hydration: 1-2 L fluid infused for 8-12 hr before dose
- May use concomitant amifostine to decrease nephrotoxicity
- Do not repeat course until SCr <1.5 mg/dL [<133 micromoles/L] or BUN <25 mg/dL [<8.93 mmol/L] or WBC >4000/mm³ AND platelets >100 k/mm³
Interactions
Tacrolimus , Cetuximab , Acetaminophen , Ibuprofen , Aspirin , Cidofovir , Altretamine , (Vitamin B6 (Pyridoxine , Palifermin , Amphotericin B Deoxycholate , Vitamin A , Teicoplanin | Targocid , Ziprasidone , Meglumine Compound , Dofetilide , thiotepa , novafen , Bumetanide , Adenovirus types 4 and 7 live, oral , Diatrizoate (Amidotrizoic acid) , Bendroflumethiazide , Plazomicin , Ioxaglate , Iothalamate Meglumine , Blonanserin , Meningococcal conjugate vaccine , sirukumabAlerts
• The drug should be administered under the supervision of an experienced cancer chemotherapy physician
• Severe nephrotoxicity, myelosuppression, and nausea and vomiting are dose related
• Significant ototoxicity, manifested by tinnitus and occasionally deafness, reported in children
• Anaphylactic-like reactions have occurred. Facial edema, bronchoconstriction, tachycardia, and hypotension may occur within minutes of cisplatin administration
• Failure to differentiate daily doses from total dose per treatment cycle may result in cisplatin overdose
Points of recommendation
• Cisplatin is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting.
• You may be given IV fluids for 8 to 12 hours before you receive cisplatin.
• Tell your caregivers if you feel any burning, pain, or swelling around the IV needle when cisplatin is injected.
• Cisplatin can be harmful if it gets on your skin. If skin contact occurs, wash the area with soap and water.
• You should not receive cisplatin if you have kidney disease, bone marrow suppression, or hearing loss.
• This medicine can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces.
Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.
• Avoid being near people who are sick or have infections.
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