Single Use of Rasburicase (rasb) Leads to Insufficient Tumor Lysis Syndrome (TLS) Control in Adults: Outcome and Resource Utilization in a One Year Real-Life Observational Study

TLS due to the rapid lysis of tumor cells following initiation of chemotherapy can lead to the release of intracellular components into the extracellular space. Among these hyperuricemia might exceed the excretory capacity of the kidneys and lead to renal failure. Rasb is a recombinant urate oxidase given during the first 3–5 days of chemotherapy to effectively lower uric acid serum levels. Limited data suggest that a single prechemotherapy dose of rasb might be sufficiently efficacious and this single dose regimen is widely used to reduce treatment costs.

We analyzed the clinical and economical data of all adults who received rasb for prophylaxis or treatment of TLS at a university hospital during a one year period. The goal was to describe treatment patterns and outcome outside of clinical trials and to verify whether patients with TLS can be treated cost-effectively. 38 patients (pts) received rasb, however 1/3 of the pts were treated off-label for other reasons then TLS. 24 pts (median age 66 yrs, 21 male) received rasb for malignancy-associated hyperuricemia and were eligible for further clinical and economical evaluation. 2/3 of these pts were treated for hematological malignancies (acute leukemia 6pts, lymphoma 8 pts) and 8 pts for solid tumors. Apart from hydration (mean volume 2 l per day; all pts), furosemide (mean dose 80 mg/day; all pts) and urinary alkalinization with sodium bicarbonate (pH > 7; 7 pts), 20 patients received a single 7,5 mg dose of rasb and 4 pts received multi dose. In 14 pts a tumor lysis was observed. 6 pts died, three fatalities were directly associated with TLS. Mortality was higher among pts with single dose rasb vs. multi dose rasb (30% vs. 0 %) and higher among patients with urinary alkalinization (71% vs. 5%). No anaphylaxis, hemolysis or methemoglobinemia was observed in this cohort.

The mean duration of hospitalisation was 23 days, the mean treatment costs were 16.200 €. The costs exceeded the revenues based on diagnosis related groups for Germany (G-DRG) in 18 pts and resulted in a 7% funding gap. 107.000 € were spent for drugs for these patients, 10% of these for rasb.

We conclude from this observational study that

1. TLS is a menacing disease, resulted in a 12,5 % mortality and should therefore be cautiously monitored and treated,

2. single dose rasb was associated with a higher mortality rate then multi dose,

3. urinary alkalinization cannot be recommended when rasb is used,

4. TLS leads to a 7 % underfunding in the respective G-DRGs,

5. for TLS pts. the usage of rasb elevates the total drug expenses by 10%.