CARBOPLATIN 
Pronounciation
- (KAR-boh-plah-tin)
Trade Name(s)
- Antineoplastic (alkylating agent)
Baseline studies indicated; see Monitor. See Maternal/Child.
Before giving a dose in a cycle, it is recommended that platelets be above 100,000/mm3 and neutrophils above 2,000/mm3; see Dose Adjustments. The Calvert formula for carboplatin dosing based on pre-existing renal function and/or desired platelet nadir determines the patient’s dose.
Total dose (mg) = (Target AUC) × (GFR + 25)
Dose is calculated in milligrams, not mg/M2. The ordering physician determines the target AUC (area under the curve) and supplies the required information on the GFR (glomerular filtration rate) or CrCl, as well as the desired response. The pharmacist calculates the correct dose. See package insert for additional information.
Initial treatment of advanced ovarian cancer in combination with cyclophosphamide:
Carboplatin 300 mg/M2 plus cyclophosphamide 600 mg/M2 on Day 1 every 4 weeks for 6 cycles or carboplatin dose targeted by Calvert equation to an AUC of 6 to 7 plus cyclophosphamide 600 mg/M2 on Day 1 every 4 weeks.
Palliative treatment of recurrent ovarian cancer after prior chemotherapy:
With normal renal function (CrCl greater than 60 mL/min), give 360 mg/M2 on Day 1 every 4 weeks or, alternately, a dose targeted by Calvert equation to an AUC of 4 to 6 appears to provide an appropriate dose range in these patients.
Single agent or combination therapy. Dose adjustment is based on nadir after prior dose according to the following chart.
aPercentages apply to carboplatin as a single agent or to both carboplatin and cyclophosphamide in combination. | |||||||||||||||
Once the dose has been increased to 125% of the starting dose, no further dose increases are indicated. ■ With impaired renal function (CrCl 16 to 40 mL/min), give 200 mg/M2; CrCl 41 to 59 mL/min, give 250 mg/M2. Dose recommendation not available for patients with a CrCl less than 16 mL/min. ■ Bone marrow suppression is more severe in patients who have had prior therapy, especially with cisplatin and when carboplatin is used with other bone marrow–suppressing therapies or radiation, and may be more severe in the elderly. Reduced dose may be indicated. Monitor carefully and manage dose and timing to reduce additive effects.
Specific techniques required; see Precautions.
Available as a premixed solution (10 mg/mL) and as a lyophilized powder. Immediately before use, reconstitute each 10 mg of carboplatin lyophilized powder with 1 mL of SWFI, D5W, or NS (50 mg with 5 mL, 150 mg with 15 mL, 450 mg with 45 mL). All yield 10 mg/mL. Both preparations may be further diluted with NS or D5W to concentrations as low as 0.5 mg/mL. Do not use needles or IV tubing with aluminum parts to mix or administer; a precipitate will form and decrease potency. Best to mix lyophilized preparation immediately before use.
Stable to the date indicated on the package stored at CRT and protected from light. Multidose vials maintain microbial, chemical, and physical stability for up to 14 days at RT (25° C [77° F]) following multiple-needle entries. Lyophilized powder: Store unopened vials at CRT. Protect from light. Reconstituted solutions are stable for 8 hours at RT (25° C [77° F]). Discard 8 hours after dilution.
Forms a precipitate if in contact with aluminum (e.g., needles, syringes, catheters).
Other sources suggest specific compatibilities dependent on concentration and manufacturer; consult a pharmacist.
A single dose as an infusion over a minimum of 15 minutes. Extend administration time based on amount of diluent and patient condition.
An alkylating agent. Better tolerated by patients, carboplatin causes less nausea and vomiting, less neurotoxicity, and less nephrotoxicity than cisplatin. Myelosuppression is generally reversible and manageable with antibiotics and transfusions. Produces interstrand DNA cross-links and is cell-cycle nonspecific. Not bound to plasma proteins. Half-life is 2.6 to 5.9 hours. Majority of carboplatin is excreted in the urine within 24 hours.
Initial treatment of advanced ovarian cancer in combination with other approved chemotherapeutic agents (e.g., cyclophosphamide). ■ Palliative treatment of recurrent ovarian cancer after prior chemotherapy, including patients treated with cisplatin.
Treatment of bladder cancer, non–small-cell lung cancer, and small-cell lung cancer.
Hypersensitivity to cisplatin or other platinum-containing compounds or mannitol; severe bone marrow suppression; significant bleeding.
Follow guidelines for handling cytotoxic agents. See Appendix A. ■ Usually administered by or under the direction of the physician specialist in a facility with adequate diagnostic and treatment facilities to monitor the patient and respond to any medical emergency.■ Bone marrow suppression is dose related and may be severe, resulting in infection and/or bleeding. Anemia may be cumulative and may require transfusion support. Bone marrow suppression increased in patients who have received prior therapy, especially regimens including cisplatin, and in patients with impaired kidney function.■ Anaphylaxis has been reported and may occur within minutes of administration.■ Risk of hypersensitivity increased in patients previously exposed to platinum therapy. Patients sensitive to other platinum compounds (e.g., cisplatin) may be sensitive to carboplatin; see Contraindications. ■ Peripheral neurotoxicity is uncommon, but risk may be increased in patients over 65 years of age and in patients previously treated with cisplatin. ■ Secondary malignancies, including acute nonlymphocytic leukemia, myeloproliferation syndrome, and carcinoma, have been reported in patients treated with alkylating agents. ■ See Drug/Lab Interactions.
BUN and SCr should be done before each dose. CrCl, WBC, platelet count, and hemoglobin are recommended before each dose and weekly thereafter. Platelet count recommended to be 100,000/mm3 and neutrophils 2,000/mm3 before a dose can be repeated; see Dose Adjustments. Anemia is frequent and cumulative. Transfusion is often indicated. ■ Excessive hydration or forced diuresis not required, but maintain adequate hydration and urinary output. ■ Nausea and vomiting are frequently severe but less than with cisplatin; generally last 24 hours. Prophylactic administration of antiemetics is indicated. Various protocols are used. ■ Observe for symptoms of hypersensitivity reactions during administration; epinephrine, corticosteroids, and antihistamines should be available.■ Observe closely for symptoms of infection. Prophylactic antibiotics may be indicated pending results of C/S in a febrile neutropenic patient. ■ Monitor for thrombocytopenia (platelet count less than 50,000/mm3). Initiate precautions to prevent excessive bleeding (e.g., inspect IV sites, skin, and mucous membranes; use extreme care during invasive procedures; test urine, emesis, stool, and secretions for occult blood).
Effective birth control recommended. Manufacturer provides a patient information booklet. ■ See Appendix D.
Category D: avoid pregnancy. ■ Discontinue breast-feeding. ■ Safety and effectiveness for use in pediatric patients not established. ■ Significant hearing loss has been reported in pediatric patients; occurred with higher-than-recommended doses of carboplatin in combination with other ototoxic agents.
Neurotoxicity and myelotoxicity may be more severe. ■ Consider possibility of decreased renal function. ■ See Dose Adjustments and Precautions.
Nephrotoxicity and ototoxicity are additive when used with other ototoxic or nephrotoxic agents (e.g., acyclovir, aminoglycosides [e.g., gentamicin], cisplatin, rifampin, quinidine). Use with caution. ■ Bone marrow toxicity increased with other antineoplastic agents, radiation therapy, and/or other agents that may cause blood dyscrasias (e.g., anticonvulsants [e.g., phenytoin], cephalosporins, mycophenolate, rituximab). Dose adjustment of either or both drugs may be indicated. ■ Do not administer live virus vaccines to patients receiving antineoplastic drugs. ■ See Dose Adjustments.
Allergic reactions, including anaphylaxis, can occur during administration. Alopecia (rare), anemia, anorexia, bleeding, bone marrow suppression (usually reversible), bronchospasm, bruising, changes in taste, constipation, death, decreased serum electrolytes, decreased urine output, dehydration, diarrhea, erythema, fatigue, fever, hemolytic uremic syndrome (rare, cancer-associated), hypotension, infection, laboratory test abnormalities (alkaline phosphatase, aspartate aminotransferase [AST], BUN, SCr, total bilirubin), nausea and vomiting (severe), neutropenia, ototoxicity, peripheral neuropathies, pruritus, rash, stomatitis, thrombocytopenia, urticaria, visual disturbances, weakness.
Notify physician of all side effects. Symptomatic and supportive treatment is indicated. Withhold carboplatin until myelosuppression has resolved. Administration of whole blood products (e.g., packed RBCs, platelets, leukocytes) may be required. Blood modifiers (e.g., darbepoetin alfa, epoetin alfa, filgrastim, pegfilgrastim, sargramostim) may be indicated to treat bone marrow toxicity. Treat anaphylaxis with epinephrine, corticosteroids, oxygen, and antihistamines. There is no specific antidote.