ORLANDO—Novel dosing regimens of rasburicase can prevent tumor lysis syndrome (TLS) at costs that are much lower than conventional dosing, according to studies presented at the 2010 American Society of Hematology Annual Meeting & Exposition.
Rasburicase is a recombinant urate oxidase approved for the prevention of TLS, an oncologic emergency that produces metabolic disturbances and the potential for acute renal failure and death. Currently, rasburicase is US Food and Drug Administration (FDA)- approved for prevention. In adults, the recommended dose is 0.2 mg/kg intravenous (IV) per day up to 5 days, which translates into more than $5100 for treatment of a 75-kg person.
Low Dose versus Standard Dose
Investigators from the Mayo Clinic in Rochester, Minnesota, evaluated the effectiveness of the 0.1-mg/kg dose as compared with the recommended dose in the prevention of TLS among 125 cancer patients receiving rasburicase on the first day of chemotherapy. The drug was dosed at either 0.1 mg/kg (low dose) or 0.2 mg/kg (standard dose), per clinician discretion, and was repeated as necessary. Additional doses were required in 14.6% of the low-dose patients and in 21.4% of the standarddose patients, which was not a significant difference.
Although reduction in uric acid, the intended effect, was higher with the standard dose (97.1% vs 88.7%; P = .002), renal outcomes were similar, re - ported Alfonso Eirin, MD.
“The low-dose patients received an average of 6 mg per dose versus 12 mg in the standard group. This represents a savings of $2601 per patient,” he said. Treatment of a 75-kg patient with the standard dose costs $6504, which is lowered to just $3252 using the lower dose.
Only the standard-dose patients experienced renal insufficiency (7.4%). Rates of dialysis were numerically higher with the standard dose but not significantly different (18.6%) compared with 7.3% with the low dose (P = .07). Dialysis often was initiated for hyperkalemia and hyperphosphatemia. Only 12.5% of doses were started for elevations in serum creatinine.
“Our results suggest that low-dose rasburicase may be as effective as 0.2 mg/kg. While high-dose rasburicase was more effective at reducing uric acid, it did not reduce the need for dialysis because dialysis was often precipitated for hyperkalemia and hyperphosphatemia, which rasburicase does not affect,” Eirin explained. “Despite bias, our results suggest low-dose rasburicase may be a viable alternative and the potential savings could be enormous.”
Single-Dose Approach Effective and Less Expensive
Since rasburicase came to market, various studies have examined single doses (3 mg and 6 mg) in the adult population, in an effort to find a dosing regimen that is as effective as the FDA-approved dose but less expensive. A single-center study evaluated a 4.5- mg dose for its ability to lower uric acid levels versus the conventional weightbased approach and to determine its cost-effectiveness. The results were reported by Barbara Yim, PharmD, BCOP, of the John H. Stroger Jr. Hospital of Cook County, Chicago.
“The cost of rasburicase is a problem for us. We found that using a single dose could save our hospital a lot of money,” Yim commented (Table).
The retrospective study included 25 patients with hematologic malignancies receiving chemotherapy or planning to initiate chemotherapy within 24 hours of rasburicase administration. Patients at low risk for TLS were excluded.
There were 30 hyperuricemic events, and 93% were successfully managed with the single dose of rasburicase. Responders were defined as patients achieving more than a 50% reduction in the uric acid level at 24 hours, 48 hours, or 96 hours. Three patients required a second dose to achieve response