Tumor Lysis Syndrome: Prophylactic Strategies

Video

An overview of the prophylactic strategies that may be utilized to reduce the likelihood of tumor lysis syndrome.

Transcript:

Anthony Perissinotti, PharmD, BCOP: There are many different approaches to prophylaxis of tumor lysis syndrome and it really depends on the risk of the patient. I’ll just describe high-risk patients because low-risk patients probably don’t need much prophylaxis at all. Intermediate-risk patients for the most part, I’m approaching them similarly to our high-risk patients. I start everyone on a xanthine oxidase inhibitor, regardless of what their uric acid level is. So I start them on allopurinol. I also start them on fluids, 100 to 150 ml per hour. I watch their electrolytes. If I have to go up, I have to go up. If they are getting fluid overloaded, I’ll give them Lasix [furosemide]. If their uric acid looks great in a day I’ll bring down the fluids, but at least I start on 100 to 150 ml for most patients. Certainly patients with cardiac disorders, heart failure, I might be a little bit more ginger with their fluids. I start [those] before starting chemotherapy.

I don’t start a phosphate binder as prevention I wait for the phosphorus to go up. I also don’t start rasburicase prophylaxis even in high-risk patients. Now this is a contentious debate. I think many experts would disagree with me and many guidelines would suggest all high-risk patients should get rasburicase regardless if the uric acid. I don’t use it as prevention I use it as treatment. It’s a very effective medication and if you’re monitoring patients labs every 6 hours or even 8 hours and you see that uric acid start to rise rapidly you can instantaneously give them rasburicase and the uric acid will go down to zero and so for that reason I don’t use it for prevention.

For the prevention and treatment of tumor lysis syndrome, there is no better strategy than to hydrate patients. Hydrating means giving them normal saline. Decades ago we thought that potentially alkalizing urine to make it more basic could help tumor lysis because the uric acid was more soluble. Now that we have very effective uric acid lowering agents that’s no longer the case. It’s less of a debate now whether you choose a sodium bicarbonate vs normal saline. I use normal saline. The field has moved in the direction of using normal saline because with an alkaline urine your phosphorus and your calcium phosphorus can actually become less soluble and therefore deposit more inside the kidneys. So we use normal saline to prevent and tumor lysis. It’s by far the most effective way to prevent and treat tumor lysis.

For prevention I generally will start a patient 100 too 150 ml per hour of normal saline and I adjust as needed. For treatment it’s much higher, 200 to 300 ml per hour. The goal here is not necessarily hypervolemia, our goal is to keep a patient euvolemic because what we’re trying to do is just flush out all of the electrolytes. There are times a patient can get fluid overloaded and it’s very important to monitor for this because we don’t want our patients to have flash pulmonary edema. So we provide our patients with diuretics as well.

I think one thing that no one ever talks about for prevention is debulking the patient. Starting things like steroids or hydroxyurea or even doing luciferases to pull off hundreds of thousands of blood cells. Trying to debulk that patient so that when you do start definitive therapy the disease burden is much less that it was 2, 3, 4 days ago while you were waiting for a definitive diagnosis. So I think debulking is very important for the prevention of tumor lysis as well.

Of course, we limit potassium in patients’ diets at least 24 or 72 hours around chemotherapy. I don’t use phosphorus binders for the prevention of tumor lysis but I will use it when my patient’s phosphorus starts to rise, as treatment. There are a number of phosphorus binders out there. There’s sevelamer, there’s calcium based, lanthanum based, and aluminum based drugs. I typically just used Sevelamer. It’s probably the weakest of all the binders but it’s what I tend to use. The way these drugs tend to work is they bind to phosphorus in your stomach, so it’s binding dietary phosphorus. They don’t work all that well because when you think about it the phosphorus is actually being released in your bloodstream not from your gut. So It might help prevent you absorbing more phosphorus, but really it’s the fluids that are going to get rid of your phosphorus. In worst-case scenarios if we can’t deal with the phosphorus with our fluid and our phosphate binders, that’s when we have to get a nephrologist on board to pull off these electrolytes with dialysis.

There are also agents that can help lower potassium, which in general we’re treating hyperkalemia just like you would on any other unit, but this is probably the most important electrolyte to monitor because this is the one that can cause sudden cardiac death and arrhythmia. We want to pull out our insulin and dextrose as soon as feasible based off of how high their potassium [levels] are. Essentially you’re just pushing potassium into the cell with the insulin and then you use dextrose to prevent hypoglycemia from the insulin.

Then we have our uric acid—lowering agents like allopurinol or febuxostat. These are our xanthine oxidase inhibitors, they prevent the conversion of xanthine and hypoxanthine to uric acid. Then we have rasburicase which is an enzyme that helps convert uric acid that has already been made or is being released from the cells. It converts uric acid to a molecule called allantoin. Allantoin is much more water-soluble and you are able to excrete it through your kidneys a lot easier than uric acid. Uric acid can clog the kidneys and cause renal failure.

Transcript edited for clarity.

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