James Short, MD, and John Reagan, MD, highlight guideline-indicated treatment options for patients with or at risk of tumor lysis syndrome.
Nicholas James Short, MD: Actually leading into that…there’s very little evidence in this space— there’s not a lot of studies, but maybe talk about some of the data that can guide some of our practice and some of the things I already mentioned in terms of preventive measures for patients who might be at risk for development of tumor lysis syndrome [TLS].
John L. Reagan, MD: Sure. So, like you said before, the key thing is keeping that urine output going and doing whatever you can to keep the urine output going. Then, like you said, with the phosphate bonders and using things like either Lokelma (Sodium zirconium cyclosilicate) or Kayexalate (polystyrene sulfonates) to try get rid of the potassium if it gets too high. But really the hallmark of TLS treatment is preventing uric acid from going up too high. The first drug that we always reach for is allopurinol. …The mechanism of action is involved in purine catabolism. Purine, if you remember back to first and second years of medical school, purine goes to hypoxanthine to xanthine, and then through xanthine oxidase it gets turned into uric acid. And what allopurinol does is, it’s a xanthine oxidase inhibitor, so it keeps things at [a normal] xanthine level. So, you’re not actually making uric acid.
The other drug that’s approved is febuxostat, which is also a xanthine oxidase inhibitor, very much the same as allopurinol. We’ll talk in a second about how all those work. But once you have uric acid, like you talked about before, our bodies can’t get rid of uric acid. Humans and higher-level primates don’t have an ability to get rid of uric acid, so what we [do is] leverage that rasburicase, which is like urate oxidase, which is what converts uric acid to allantoin and helps your body then excrete out the uric acid so you can finally get rid of it.
Those are really the hallmark treatments, giving some sort of allopurinol or febuxostat and rasburicase. Allopurinol goes back to the 1960s when it was first looked at for treatment of really elevated uric acid levels and it was found to effectively lower uric acid levels, so that became the gold standard. The initial reports for rasburicase came out of pediatric literature and, like with most things with pediatrics, was on a mg/kg basis for dosing. There was a later study by Dr [Jorge] Cortes out of MD Anderson [Cancer Center] in the Journal of Clinical Oncology. It was randomized and patients got randomized to either allopurinol, allopurinol plus rasburicase or rasburicase. That study showed that you were able to effectively lower uric acids much better with the addition of rasburicase. So, allopurinol was able to lower it a little bit, but rasburicase could really effectively eliminate your uric acid levels. Interestingly, in that study though, I wasn’t able to find anything in terms of renal replacement therapy or the need for that renal replacement therapy. So, that’s always something to kind of think about in the back of your mind.
Then [INAUDIBLE] oncology in 2015 did allopurinol vs febuxostat. With this study, they showed that there was really no tremendous difference in terms of uric acid levels. Once again, it was a randomized study, but there was no tremendous difference in terms of uric acid levels in these patients. And I think that’s the big take home. There were maybe some signs of cardiac issues with febuxostat populations when they get treated, but I think the big issue and the reason that we don’t usually use this drug is because of the cost. It’s an order of magnitude higher in terms of cost, so our clinical pharmacists, who are so essential in terms of helping us treat tumor lysis syndrome, usually shy away from this drug and really help us in terms of allopurinol dose and what’s an effective dosing for those patients. So these, allopurinol and rasburicase, are probably our most-used drugs for this.
Transcript edited for clarity.