Cisplatin – Uses, Dosage, Side Effects, Interaction

Cisplatin is the prototype platinum coordination complex classified as an alkylating agent and used intravenously in the treatment of several forms of cancer. Cisplatin has been associated with a low rate of serum enzyme elevations and with rare cases of clinically apparent, acute liver injury.

Cisplatin is a chemotherapy drug used to treat testicular, ovarian, bladder, head and neck, lung and cervical cancer. It may also be used to treat other cancers. It is best to read this information with our general information about chemotherapy and the type of cancer you have.

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 action

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, and 3) the induction of mispairing of the nucleotides leading to mutations.

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.

Indications

  • For the treatment of metastatic testicular tumors, metastatic ovarian tumors, and advanced bladder cancer.
  • Mantle cell lymphoma that has relapsed (come back) or is refractory (does not respond to treatment).
  • Precursor B lymphoblastic leukemia (a type of acute lymphoblastic leukemia) has relapsed or is refractory.
  • Advanced Ovarian Cancer
  • Ovarian Cancer Metastatic
  • Advanced Bladder cancer
  • Advanced Testicular cancer
  • Metastatic Testicular cancer

Use in Cancer

Cisplatin is approved to be used alone or with other drugs to treat:

  • Bladder cancer. It is used alone in patients with advanced cancer that cannot be treated with other therapies, such as surgery or radiation therapy.
  • Ovarian cancer has spread to other parts of the body. It is used with other drugs in patients who have already had surgery or radiation therapy. It is used alone in patients whose cancer has not gotten better with standard chemotherapy and who have not received previous cisplatin.
  • Testicular cancer has spread to other parts of the body. It is used with other drugs in patients who have already had surgery or radiation therapy.

Cisplatin is also being studied in the treatment of other types of cancer.

Contraindications

  • are allergic to cisplatin, any platinum-containing compounds, or any ingredients of the medication
  • have hearing impairment
  • have reduced bone marrow function (e.g. low white cells)
  • have reduced kidney function
  • Severe hypersensitivity to cisplatin or platinum compounds would preclude its administration; cisplatin is contraindicated in patients who have had severe hypersensitivity reactions, and rechallenge is not a recommendation.
  • Cisplatin has been shown to cross the placenta and may cause fetal harm. Women of reproductive age should use reliable contraception during treatment and up to a year from the final treatment date.
  • Cisplatin is also present in the breast milk of lactating women on a cisplatin regimen. Breastfeeding is not recommended during treatment. If hypersensitivity occurs, the provider should discontinue cisplatin immediately.
  • a bad infection
  • acute leukemia
  • low amount of magnesium in the blood
  • low amount of calcium in the blood
  • low amount of sodium in the blood
  • low amount of potassium in the blood
  • hemolytic uremic syndrome, a condition that affects the kidney and the blood
  • anemia
  • decreased blood platelets
  • low levels of white blood cells
  • a painful condition that affects the nerves in the legs and arms called peripheral neuropathy
  • sudden blindness and pain upon moving the eye
  • ototoxicity, damage to the inner ear that affects hearing or balance
  • hearing loss
  • a heart attack
  • a clot in the lung
  • a stroke
  • inflammation of blood vessels in the brain or spinal cord
  • Raynaud’s phenomenon, a condition where blood vessels constrict too much with coldness or stress
  • blood clot in a deep vein of the extremities
  • thrombotic thrombocytopenic purpura, a type of blood disorder
  • decreased kidney function
  • vomiting
  • amount of uric acid in the blood
  •  pregnancy
  • a patient who is producing milk and breastfeeding
  • TPMT poor metabolizer
  • a type of brain disorder called posterior reversible encephalopathy syndrome
  • a clot in the aorta
  • kidney disease with likely reduction in kidney function

Dosage

Strengths: 50 mg; 10 mg; 1 mg/mL

Testicular Cancer

  • 20 mg/m2 by slow IV infusion daily for 5 days per cycle in combination with other approved chemotherapeutic agents

Ovarian Cancer

  • 75 to 100 mg/m2 by slow IV infusion once every 3 to 4 weeks on Day 1

Bladder Cancer

  • 50 to 70 mg/m2 by slow IV infusion once every 3 to 4 weeks; for heavily pretreated patients, an initial dose of 50 mg/m2 by slow IV infusion once every 4 weeks is recommended

FDA Approved Adult Dosing Regimens

  • Advanced testicular cancer: 20 mg.m^2 IV for a single dose on day 1 of a 21 or 28-day cycle; maximum 100 mg/m^2 per cycle.
  • Advanced bladder cancer: 50 to 70 mg.m^2 IV for a single dose on day 1 of a 21 or 28-day cycle; maximum 100 mg/m^2 per cycle.
  • Advanced ovarian cancer: 100 mg.m^2 IV for a single dose on day 1 of a 21 or 28-day cycle; maximum 100 mg/m^2 per cycle.

Cisplatin can be used as monotherapy or as part of a multi-drug regimen. Patients should have proper hydration while monitoring urine output before, during, and for 24 hours following administration.

Renal Dose Adjustments

  • Creatinine clearance between 10 and 50: decrease dose by 25%
  • Creatinine clearance below 10: decrease dose by 50%
  • Hemodialysis: Decrease the dose by 50% with no supplement; administer after dialysis on dialysis days with no supplement
  • Peritoneal dialysis: Decrease the dose by 50% with no supplement

Side Effects

The Most Common

  • nausea
  • vomiting
  • diarrhea
  • hair loss
  • loss in ability to taste food
  • hiccups
  • dry mouth, dark urine, decreased sweating, dry skin, and other signs of dehydration
  • swelling, pain, redness, or burning at the injection site
  • pain, burning, or tingling in the hands or feet
  • muscle cramps
  • difficulty walking
  • feeling of an electric-like shock when you bend your neck forward
  • seizures
  • sudden changes in vision, including color vision
  • loss of vision
  • eye pain
  • chest pain or pressure
  • fever, sore throat, chills, or other signs of infection
  • unusual bleeding or bruising
  • black and tarry stools
  • red blood in stools
  • bloody vomit
  • vomited material that looks like coffee grounds

More Common

  • loss of appetite
  • nausea and vomiting
  • taste disturbances
  • temporary hair loss
  • blurred vision
  • diarrhea
  • difficulty in the ability to distinguish colors
  • difficulty walking
  • hearing difficulties
  • loss of balance
  • loss of reflexes
  • muscle cramps
  • numbness or tingling in fingers or toes
  • ringing in ears
  • severe nausea and vomiting
  • unusual tiredness or weakness
  • walking problems

Rare

  • pain, redness, or swelling at the site of injection
  • seizures
  • signs of a serious allergic reaction (difficulty breathing, wheezing, swelling of the face and throat, increased heart rate, dizziness)
  • signs of bleeding (e.g., unusual bruising or bleeding, pinpoint red spots on the skin, black tarry stools, bloody nose, blood in urine, coughing blood, cuts that don’t stop bleeding)
  • signs of infection (symptoms may include fever or chills, sore throat, severe diarrhea, shortness of breath, prolonged dizziness, headache, stiff neck, weight loss, painful or difficult urination, or listlessness)
  • pain, burning, redness at the injection site,
  • numbness, tingling, coldness or blue discoloration of the hands or feet,
  • pain, redness, swelling of arms or legs,
  • loss of reflexes,
  • loss of balanced,
  • trouble walking,
  • muscle cramps or spasms,
  • weakness,
  • neck or back pain,
  • mouth or tongue sores,
  • joint pain,

Drug Interaction

Pregnancy and Lactation

FDA Pregnancy category D

Pregnancy

There is a possibility of birth defects if either the man or woman is using cisplatin at the time of conception, or if it is taken during pregnancy. This medication should not be used during pregnancy unless the benefits outweigh the risks. Use effective birth control while you are being treated with this medication. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding

This medication passes into breast milk. Women receiving this medication should not breastfeed.

How should this medicine be used?

Cisplatin injection comes as a solution (liquid) to be injected over 6 to 8 hours intravenously (into a vein) by a doctor or nurse in a medical facility. It is usually given once every 3 to 4 weeks.

What special precautions should I follow?

Before taking cisplatin,

  • tell your doctor and pharmacist if you are allergic to cisplatin, carboplatin (Paraplatin), any other medications, or any of the ingredients in cisplatin injection. Ask your pharmacist for a list of the ingredients.
  • tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: amphotericin B (Abelcet; AmBisome; Amphotec, Fungizone Intravenous), anticonvulsants such as phenytoin (Dilantin), bumetanide (Bumex), ethacrynic acid (Edecrin), furosemide (Lasix), pyridoxine (Vitamin B-6). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with cisplatin, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
  • tell your doctor if you have kidney disease or hearing problems. Your doctor may not want you to receive cisplatin injection.
  • tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. You should not become pregnant or breast-feed while you are receiving cisplatin. If you become pregnant while receiving cisplatin, call your doctor. Cisplatin may harm the fetus.

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breastfeeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Blood clotting: This medication can reduce the number of platelet cells in the blood and increase your risk of bleeding. Tell your doctor immediately if you notice any signs that your blood is not clotting as quickly as usual (e.g., black and tarry stools, blood in the urine, easy bruising, or cuts that won’t stop bleeding). Your doctor will do blood tests regularly to monitor the number of platelets in your blood.

Gout: This medication may cause high levels of uric acid in the blood, making gout more likely to occur. If you have gout or a history of gout, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. Report any unusual joint pain or swelling to your doctor as soon as possible.

Hearing impairment: This medication can cause permanent hearing damage and should not be given to anyone with hearing impairment. Your hearing will be monitored closely while you are using this medication.

Infection: In addition to killing cancer cells, this medication can reduce the number of cells that fight infection in the body (white blood cells). If possible, avoid contact with people with contagious infections. Tell your doctor immediately if you notice signs of an infection, such as fever or chills, severe diarrhea, shortness of breath, prolonged dizziness, headache, stiff neck, weight loss, or listlessness. Your doctor will do blood tests regularly to monitor the number of specific types of blood cells in your blood.

Kidney function: Cisplatin can reduce kidney function and cause kidney damage. For this reason, it is very important to drink plenty of fluids right after your treatment. Your doctor may want you to drink extra fluids while taking this medication in order to help you pass more fluid and protect your kidneys. Your doctor will monitor your kidney function closely while you are using this medication. If you have reduced kidney function you should not use this medication.

Nervous system: Cisplatin can cause damage to the nervous system. If you experience symptoms such as loss of taste, tingling in the hands or feet, or balance trouble, tell your doctor as soon as possible. These side effects are often reversible if the medication is stopped early.

References

  1. https://www.cancer.gov/about-cancer/treatment/drugs/cisplatin
  2. https://www.ncbi.nlm.nih.gov/books/NBK547695/
  3. https://www.webmd.com/drugs/2/drug-8756/cisplatin-intravenous/details/list-contraindications
  4. https://en.wikipedia.org/wiki/Cisplatin
  5. https://go.drugbank.com/drugs/DB00515
  6. https://medlineplus.gov/druginfo/meds/a684036.html
  7. https://www.drugs.com/mtm/cisplatin.html
  8. CompTox Chemicals Dashboard Chemical Lists
  9. PubChem

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