Tumor lysis syndrome is an oncologic emergency characterized by severe electrolyte abnormalities, high uric acid levels, and can result in kidney failure. It typically occurs in patients with acute hematologic malignancies after the initiation of chemotherapy. The cytotoxic drugs cause massive tumor cell death, which in turn releases large amounts of potassium, phosphate and DNA into the circulation. The purines in DNA are metabolized to uric acid, which can acutely rise to very high levels, with urate crystallization in the kidneys as a result.
Although tumor lysis syndrome is most commonly observed in patients with high-grade lymphoproliferative malignancies, including acute lymphocytic leukemia and Burkitt's lymphoma, it has also been reported in many solid tumors, including lung and breast cancer. The hyperuricemia associated with tumor lysis syndrome tends to develop around two to three days after the initiation of chemotherapy, although some patients with very high tumor loads can present with elevated uric acid and signs of renal failure.
Treatment of elevated uric acid in hyperuricemia consists of both inhibition of uric acid synthesis and promotion of uric acid clearance. Allopurinol is used as a front line therapy, at a dose of up to 800 mg daily. Rasburicase (Elitek®, Sanofi-Aventis), an unpegylated recombinant uricase, is approved for “the initial management of plasma uric acid levels in pediatric patients with leukemia, lymphoma, and solid tumor malignancies who are receiving anticancer therapy expected to result in tumor lysis and subsequent elevation of plasma uric acid” (Elitek product label). This is currently the only approved indication for any uricase preparation in the United States. While rasburicase, administered via IV infusion, has been shown to be quite effective at lowering uric acid levels in patients suffering from tumor lysis syndrome, it requires multiple doses and is not typically used for prophylaxis of at-risk patients.