Usual Adult Dose for 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

Comments:

• 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.

Uses:

• 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

These dosing recommendations apply to the initial course of therapy; adjust subsequent doses according to patient tolerance based on the degree of bone marrow suppression.

Liver Dose Adjustments

Data not available

Dose Adjustments

Pretreatment platelet count and performance status are important prognostic factors for 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 posttreatment 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.

Precautions

US BOXED WARNINGS:

• This drug should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents in an adequate treatment facility.
• 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.
• Vomiting is a frequent side effect.
• Anaphylactic reactions to this drug have been reported and may occur within minutes of administration; epinephrine, corticosteroids, and antihistamines alleviate symptoms.

CONTRAINDICATIONS:

• 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

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Storage requirements:

• Store unopened vials at 25C (77F); excursions permitted from 15 to 30C (59 to 86F). Protect from light.

Reconstitution/preparation techniques:

• Injection multi-dose vials maintain microbial, chemical, and physical stability for up to 14 days at 25C following multiple needle entries.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.
• Solutions for infusion should be discarded 8 hours after preparation.

IV compatibility:

• The manufacturer product information should be consulted.

General:

• To minimize the risk of dermal exposure, wear impervious gloves when handling vials.
• If this drug contacts the skin, immediately wash thoroughly with soap and water. -If this drug contacts mucous membranes, the membranes should be flushed immediately and thoroughly with water.
• Aluminum reacts with carboplatin injection causing precipitate formation and loss of potency; therefore, needles or IV sets containing aluminum parts that may come in contact with the drug should not be used for preparation or administration.

Frequently asked questions

• Why give Taxol (Paxel) before carboplatin?
• Does carboplatin cause neuropathy?
• How does carboplatin stop cancer?