Carboplatin – Uses, Dosage, Side Effects, Interaction

Carboplatin is an organoplatinum antineoplastic alkylating agent used in the treatment of advanced ovarian carcinoma. Carboplatin has a long duration of action as it is given every 4 weeks and has a narrow therapeutic? index. Patients should be counseled regarding bone marrow? suppression and anemia?.

Use in Cancer

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

• Ovarian cancer is advanced. It is used with other chemotherapy as a first-line treatment. It is used alone as palliative treatment for the disease that has recurred (come back) after earlier chemotherapy.

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

Contraindications

• are sensitive or allergic to carboplatin or any ingredients of the medication
• are sensitive or allergic to platinum-containing compounds
• have severely reduced bone marrow function
• have severely reduced kidney? function
• Hypersensitivity to the active component, any of the ingredients, or platinum-containing compounds
• Additional and/or more frequent monitoring? should be done to ensure receipt of an effective dose while avoiding unnecessary toxicities
• Severe? bone marrow depression
• Severe bleeding
• a bad infection?
• decreased function of bone marrow
• anemia
• an increased risk of bleeding
• decreased blood platelets
• low levels of white blood cells
• low levels of a type of white blood cell called neutrophils
• a painful condition that affects the nerves in the legs and arms called peripheral neuropathy?
• hearing loss
• bleeding
• liver problems
• decreased kidney function
• excessive vomiting
• abnormal liver function tests
• pregnancy
• a patient who is producing milk and breastfeeding

Dosages

Strengths: 10 mg/mL; 50 mg; 150 mg; 450 mg

Ovarian Cancer

SINGLE AGENT THERAPY for use in the treatment of recurrent ovarian cancer:

• 360 mg/m2 by IV on day 1 every 4 weeks (alternatively, the carboplatin dose may be calculated by the Calvert formula below). Usually, single intermittent courses should not be repeated until the neutrophil? count is at least 2000 and the platelet? count is at least 100,000.

COMBINATION THERAPY (with cyclophosphamide) for use in the treatment of advanced ovarian cancer (an effective combination for previously untreated patients):

• Carboplatin: 300 mg/m2 by IV on day 1 every 4 weeks for 6 cycles (alternatively, the carboplatin dose may be calculated by the Calvert formula below)
• Cyclophosphamide 600 mg/m2 IV on day 1 every 4 weeks for 6 cycles
• Intermittent courses of carboplatin in combination with cyclophosphamide should not be repeated until the neutrophil count is at least 2000 and the platelet count is at least 100,000.
• FORMULA DOSING: Another way to determine the initial dose is the use of a mathematical formula based on a patient’s preexisting renal? function or renal function and desired platelet nadir (renal excretion is the major route of elimination for this drug). The use of this formula allows compensation for patient variations in pretreatment renal function that might otherwise result in either under-dosing (in patients with above-average renal function) or overdosing (in patients with impaired renal function).
• CALVERT FORMULA: Total Dose (mg) = (target AUC) x (GFR + 25); Note: With the Calvert formula, the total dose of carboplatin is calculated in mg, not mg/m2
• This drug is usually administered by an infusion lasting 15 minutes or longer.
• No pre- or post-treatment hydration or forced diuresis is required.
• The target AUC of 4 to 6 mg/mL/min using single-agent carboplatin appears to provide the most appropriate dose range in previously treated patients.
• To avoid potential toxicity due to overdosing, if a patient’s GFR is estimated based on serum creatinine? measured by the standardized Isotope Dilution Mass Spectrometry (IDMS) method rather than using an actual GFR measurement, a capping of the dose of carboplatin for the desired exposure (AUC) has been recommended.
• For the initial treatment of advanced ovarian carcinoma in established combination with other approved chemotherapeutic agents. One established combination regimen consists of carboplatin and cyclophosphamide.
• For the palliative treatment of patients with ovarian carcinoma recurrent after prior chemotherapy, including patients who have been previously treated with cisplatin.

Renal Dose Adjustments

Patients with Impaired Kidney Function:

• Patients with creatinine clearance? values below 60 mL/min are at increased risk of severe bone marrow suppression. In renally-impaired patients who received single-agent carboplatin therapy, the incidence of severe leukopenia?, neutropenia?, or thrombocytopenia has been about 25% when the dosage modifications in the table below have been used.
• CrCl 41 to 59 mL/min: The recommended dose on Day 1 is 250 mg/m2
• CrCl 16 to 40 mL/min: The recommended dose on Day 1 is 200 mg/m2
• CrCl less than 15 mL/min: Data not available

Dose Adjustments

Pretreatment platelet count and performance status are important prognostic factors for the severity of myelosuppression in previously treated patients. The suggested dose adjustments for single agent or combination therapy shown below are modified from controlled trials in previously treated and untreated patients with ovarian carcinoma. Blood counts were done weekly, and the recommendations are based on the lowest post-treatment platelet or neutrophil value:

• Platelets greater than 100,000 and neutrophils greater than 2000: Adjust dose from prior course to 125%
• Platelets 50,000 to 100,000 and neutrophils 500 to 2000: No adjustment
• Platelets less than 50,000: adjust dose from prior course to 75%

NOTE: Percentages apply to carboplatin as a single agent or to both carboplatin and cyclophosphamide in combination. In studies, dosages were also adjusted at a lower level (50% to 60%) for severe myelosuppression. Escalations above 125% were not recommended.

Side Effects

The Most Common

• nausea
• vomiting
• diarrhea
• constipation
• black, tarry, or bloody stools
• bloody vomit or vomited material that looks like coffee grounds
• unusual bruising or bleeding
• decreased urination
• pain, burning, or tingling in the hands or feet
• ringing in ears and difficulty hearing
• sores in the mouth and throat
• pain, burning, or tingling in the hands or feet
• pain, itching, redness, swelling, blisters, or sores in the place where the medication was injected
• hair loss
• pain
• weakness
• loss in ability to taste food
• pale skin
• unusual tiredness or weakness
• fainting
• dizziness
• sudden changes in vision, including color vision
• decreased urination
• swelling of the face, arms, hands, feet, ankles, or lower legs
• shortness of breath with everyday activity or when lying flat
• ringing in ears and difficulty hearing

More Common

• low magnesium–dizziness, irregular heartbeats, feeling jittery, muscle cramps, muscle spasms, cough or choking feeling.
• bleeding and reduced blood cells, including reduced red blood cells (anemia) and platelets (needed for proper blood clotting), which may be severe enough to require a blood transfusion. You should tell your doctor right away if you notice any unusual bruising or bleeding, including black tarry stools or blood in the urine.
• infection – carboplatin can temporarily lower the number of white blood cells in your blood, increasing the risk of infection;
• life-threatening allergic reaction – during and after treatment the doctor or nurse will observe you carefully for signs of allergic reaction;
• kidney and liver problems;
• loss of hearing or ringing in the ears;

Rare

• bleeding
• unusual bruising or bleeding, black tarry stools, or blood in the urine;
• infection;
• life-threatening allergic reaction;
• kidney and liver problems; or
• loss of hearing or ringing in the ears.
• low blood cell counts;
• nausea, vomiting;
• abnormal liver function tests;
• low magnesium;
• temporary hair loss; or
• pain or weakness
• signs of bleeding (e.g., bloody, black, or tarry stools, vomiting blood or material that looks like coffee grounds, blood in the urine, unusual bruising or bleeding, cuts that won’t stop bleeding, nosebleeds)
• signs of kidney problems (e.g., increased urination at night, decreased urine production, blood in the urine, change of urine color)
• skin rash or itching
• signs of a skin reaction at the injection site (e.g., red streaks along the vein where medication was injected, pain at the injection site, redness, or warmth at the site of injection)
• signs of infection (e.g., fever or chills, severe diarrhea, shortness of breath, prolonged dizziness, headache, stiff neck, weight loss, or listlessness, cough, or hoarseness)
• symptoms of vaso-occlusive disease (e.g., fluid buildup in the abdomen, swelling, yellowing of the skin or eyes, rapid weight gain)

Drug Interaction

Pregnancy and Lactation

Pregnancy category D

Pregnancy

If you are pregnant or think you might be pregnant, or if you are breastfeeding, let your doctor know right away. Carboplatin may harm your developing fetus or breastfeeding baby. If you are a woman of childbearing age, you should use birth control to avoid getting pregnant while you are taking carboplatin.

Lactation

Most sources consider that mothers receiving antineoplastic therapy should not breastfeed, especially with alkylating agents such as carboplatin.[1] It might be possible to breastfeed safely during intermittent therapy with an appropriate period of breastfeeding abstinence, but the duration of abstinence is not clear. Platinum in milk may increase with repeated courses of chemotherapy and the exact form(s), and toxicity of platinum excreted into breastmilk are also not known. The nursing infant would receive platinum compounds orally rather than intravenously and oral absorption of platinum compounds by infants is not known. It appears that it is not safe to breastfeed after carboplatin chemotherapy, and breastfeeding should probably be discontinued.

References