A review of tumour lysis syndrome with targeted therapies and the role of rasburicase

Abstract

Summary What is known and Objective: Tumour lysis syndrome (TLS) is an oncologic emergency with potentially devastating consequences classically associated with cytotoxic chemotherapy. In recent years, molecularly targeted drugs have assumed an increasingly important role in cancer therapeutics. The possibility of TLS is often overlooked in this setting. Rasburicase, a recombinant urate oxidase, is remarkably effective in treating hyperuricemia, thought to be central to the pathogenesis of renal injury in TLS. Our objective is to review the literature on TLS especially as it pertains to targeted therapies and summarize current knowledge and provide future directions regarding the role of rasburicase in the management of TLS. Methods: A MEDLINE search was conducted using PubMed and the keyphrase ‘tumor lysis syndrome’ to identify articles describing TLS with a broad range of novel anti‐cancer agents. Meeting abstracts were also reviewed. Additionally, the biomedical literature was searched using the keyword ‘rasburicase’. Results and Discussion: Tumour lysis syndrome has been described with nearly every class of ‘targeted therapy’. This is not surprising as any drug causing death of cancer cells by any mechanism may lead to TLS in the appropriate setting. Although there is a wealth of evidence suggesting that rasburicase is extremely effective in correcting hyperuricemia, prospective trials showing that it improves hard outcomes such as acute renal failure, need for dialysis and mortality are lacking. Furthermore, much lower doses and durations of therapy than approved appear to be effective in controlling hyperuricemia, potentially leading to enormous cost savings. What is new and Conclusion: Any effective cancer therapy can lead to TLS. Physicians should consider the risk of TLS on a case‐by‐case basis and determine appropriate prophylaxis. The role of rasburicase continues to evolve. Randomized controlled trials evaluating clinically relevant outcomes are needed.

Investigating Effects of Acidic pH on Proliferation, Invasion and Drug-Induced Apoptosis in Lymphoblastic Leukemia

“…In this regard, we also showed that the percentage of necrotic cells at pH 6.6 was more than that at pH 7.4. Necrosis is associated with breakdown of cancer tissues with the release of nucleic acid and other intra-cellular components which result in life threatening complications such as renal failure, arrhythmias, and seizures [43,44].…”

Successful prevention of tumor lysis syndrome using recombinant urate oxidase in patient with metastasic and bulky prostate rhabdomyosarcoma

“…In recent years, TLS has been reported in non-small cell lung cancer, breast cancer, renal cell carcinoma, gastrointestinal stromal tumor, etc. All of these cases were treated with molecular targeted agents [2]. Unfortunately, clinicians who treat patients with such tumors are often not aware of the utility of rUO for treating TLS.…”

“…On the other hand, the optimal management strategy for TLS in adult patients with epithelial cancer is poorly understood. In recent years, some patients with chemoresistant epithelial cancer have been reported to develop TLS and ARF after using molecular targeted agents [2]. If it is left undiagnosed or diagnosed too late, TLS leads to death in 20% -50% of cases.…”

Effects on Uric Acid Metabolism of the Drugs except the Antihyperuricemics

“…Rasburicase a recombinant version of uric acid oxidase has been available most recently. Rasburicase rapidly breaks down serum uric acid, and is effective in preventing and treating hyperuricemia and tumor lysis syndrome [37].…”