"The U.S. Food and Drug Administration today expanded the approved uses of Abraxane (paclitaxel protein-bound particles for injectable suspension, albumin-bound) to treat patients with late-stage (metastatic) pancreatic cancer.
Initial Treatment of Advanced Ovarian Carcinoma
PARAPLATIN (carboplatin aqueous solution) INJECTION is indicated for the initial treatment of advanced ovarian carcinoma in established combination with other approved chemotherapeutic agents. One established combination regimen consists of PARAPLATIN (carboplatin) and cyclophosphamide. Two randomized controlled studies conducted by the NCIC and SWOG with carboplatin versus cisplatin, both in combination with cyclophosphamide, have demonstrated equivalent overall survival between the two groups (see Clinical Studies).
There is limited statistical power to demonstrate equivalence in overall pathologic complete response rates and long-term survival ( ≥ 3 years) because of the small number of patients with these outcomes: the small number of patients with residual tumor < 2 cm after initial surgery also limits the statistical power to demonstrate equivalence in this subgroup.
Secondary Treatment of Advanced Ovarian Carcinoma
PARAPLATIN (carboplatin) is indicated for the palliative treatment of patients with ovarian carcinoma recurrent after prior chemotherapy, including patients who have been previously treated with cisplatin.
DOSAGE AND ADMINISTRATION
NOTE: Aluminum reacts with carboplatin causing precipitate formation and loss of potency, therefore, needles or intravenous sets containing aluminum parts that may come in contact with the drug must not be used for the preparation or administration of PARAPLATIN (carboplatin) .
PARAPLATIN (carboplatin aqueous solution) INJECTION, as a single agent, has been shown to be effective in patients with recurrent ovarian carcinoma at a dosage of 360 mg/m2 IV on day 1 every 4 weeks (alternatively see Formula Dosing). In general, however, single intermittent courses of PARAPLATIN (carboplatin) should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.
Combination Therapy with Cyclophosphamide
In the chemotherapy of advanced ovarian cancer, an effective combination for previously untreated patients consists of:
PARAPLATIN (carboplatin) —300 mg/m2 IV on day 1 every 4 weeks for 6 cycles (alternatively see Formula Dosing).
Cyclophosphamide—600 mg/m2 IV on day 1 every 4 weeks for 6 cycles. For directions regarding the use and administration of cyclophosphamide please refer to its package insert. (See Clinical Studies.)
Intermittent courses of PARAPLATIN (carboplatin) in combination with cyclophosphamide should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.
Dose Adjustment Recommendations
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 in the table 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||Neutrophils||Adjusted Dose * (From Prior Course)|
|> 100,000||> 2,000||125%|
|< 50,000||< 500||75%|
|* Percentages apply to PARAPLATIN (carboplatin aqueous solution) INJECTION as a single agent or to both PARAPLATIN and cyclophosphamide in combination. In the controlled studies, dosages were also adjusted at a lower level (50% to 60%) for severe myelosuppression. Escalations above 125% were not recommended for these studies.|
PARAPLATIN (carboplatin) is usually administered by an infusion lasting 15 minutes or longer. No pre- or post-treatment hydration or forced diuresis is required.
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.
|Baseline Creatinine Clearance||Recommended Dose on Day 1|
|41-59 mL/min||250 mg/m2|
|16-40 mL/min||200 mg/m2|
The data available for patients with severely impaired kidney function (creatinine clearance below 15 mL/min) are too limited to permit a recommendation for treatment.
These dosing recommendations apply to the initial course of treatment. Subsequent dosages should be adjusted according to the patient's tolerance based on the degree of bone marrow suppression.
Another approach for determining the initial dose of PARAPLATIN (carboplatin) is the use of mathematical formulae, which are based on a patient's pre-existing renal function or renal function and desired platelet nadir. Renal excretion is the major route of elimination for carboplatin. (See CLINICAL PHARMACOLOGY.) The use of dosing formulae, as compared to empirical dose calculation based on body surface area, allows compensation for patient variations in pretreatment renal function that might otherwise result in either underdosing (in patients with above average renal function) or overdosing (in patients with impaired renal function).
A simple formula for calculating dosage, based upon a patient's glomerular filtration rate (GFR in mL/min) and PARAPLATIN (carboplatin) target area under the concentration versus time curve (AUC in mg/mL•min), has been proposed by Calvert. In these studies, GFR was measured by 51Cr-EDTA clearance.
CALVERT FORMULA FOR CARBOPLATIN DOSING
Total Dose (mg) = (target AUC) x (GFR + 25)
Note: With the Calvert formula, the total dose of PARAPLATIN (carboplatin) is calculated in mg, not mg/m2.
The target AUC of 4 mg/mL•min to 6 mg/mL•min using single-agent carboplatin appears to provide the most appropriate dose range in previously treated patients. This study also showed a trend between the AUC of single-agent carboplatin administered to previously treated patients and the likelihood of developing toxicity.
|AUC (mg/mL•min)||% Actual Toxicity in Previously Gr 3 or Gr 4 Thrombocytopenia||Treated Patients Gr 3 or Gr 4 Leukopenia|
|4 to 5||16%||13%|
|6 to 7||33%||34%|
Because renal function is often decreased in elderly patients, formula dosing of PARAPLATIN (carboplatin) based on estimates of GFR should be used in elderly patients to provide predictable plasma PARAPLATIN (carboplatin) AUCs and thereby minimize the risk of toxicity.
PREPARATION OF INTRAVENOUS SOLUTIONS
PARAPLATIN (carboplatin aqueous solution) INJECTION is a premixed aqueous solution of 10 mg/mL carboplatin.
When prepared as directed, PARAPLATIN (carboplatin) aqueous solutions are stable for 8 hours at room temperature (25°C). Since no antibacterial preservative is contained in the formulation, it is recommended that PARAPLATIN (carboplatin) aqueous solutions be discarded 8 hours after dilution.
PARAPLATIN® (carboplatin aqueous solution) INJECTION
NDC 0015-3210-30 50 mg/5 mL aqueous solution in multidose vials (with white flip-off seals), individually cartoned.
NDC 0015-3211-30 150 mg/15 mL aqueous solution in multidose vials (with white flip-off seals), individually cartoned.
NDC 0015-3212-30 450 mg/45 mL aqueous solution in multidose vials (with white flip-off seals), individually cartoned.
NDC 0015-3216-30 600 mg/60 mL aqueous solution in multidose vials (with white flip-off seals), individually cartoned.
Unopened vials of PARAPLATIN (carboplatin aqueous solution) INJECTION are stable to the date indicated on the package when stored at 25°C (77°F); excursions permitted from 15°-30°C (59°-86°F) [see USP Controlled Room Temperature]. Protect from light.
PARAPLATIN (carboplatin aqueous solution) INJECTION multidose vials maintain microbial, chemical, and physical stability for up to 14 days at 25°C 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.
Handling and Disposal
Procedures for proper handling and disposal of anti-cancer drugs should be considered. Several guidelines on this subject have been published.1-8 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
To minimize the risk of dermal exposure, always wear impervious gloves when handling vials containing PARAPLATIN (carboplatin aqueous solution) Injection. This includes all handling activities in clinical settings, pharmacies, storerooms, and home healthcare settings, including during unpacking and inspection, transport within a facility, and dose preparation and administration.
1. ONS Clinical Practice Committee. Cancer Chemotherapy Guidelines and Recommendations for Practice. Pittsburgh, PA: Oncology Nursing Society; 1999:32-41.
2. Recommendations for the safe handling of cytotoxic drugs. Washington, DC: Division of Safety, Clinical Center Pharmacy Department and Cancer Nursing Services, National Institutes of Health; 1992. US Dept of Health and Human Services, Public Health Service Publication NIH 92-2621.
3. AMA Council on Scientific Affairs. Guidelines for handling parenteral antineoplastics. JAMA. 1985;253:1590-1592.
4. National Study Commission on Cytotoxic Exposure. Recommendations for handling cytotoxic agents. 1987. Available from Louis P. Jeffrey, ScD, Chairman, National Study Commission on Cytotoxic Exposure. Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, MA 02115.
5. Clinical Oncological Society of Australia. Guidelines and recommendations for safe handling of antineoplastic agents. Med J Aust. 1983;1:426-428.
6. Jones RB, Frank R, Mass T. Safe handling of chemotherapeutic agents: a report from The Mount Sinai Medical Center. CA Cancer J Clin. 1983;33:258-263.
7. American Society of Hospital Pharmacists. ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm. 1990;47:1033-1049.
8. Controlling occupational exposure to hazardous drugs. (OSHA Work-Practice Guidelines.) Am J Health-Syst Pharm. 1996;53:1669-1685.
Bristol-Myers Squibb Company Princeton, New Jersey 08543 USA. Rev March 2007
Last reviewed on RxList: 6/30/2009
This monograph has been modified to include the generic and brand name in many instances.
Additional Paraplatin Information
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