Therapeutic Options for TLS: A Review of Phase III Data

Transcript:

Michael R. Bishop, MD: There was an article by Jorge Cortes and colleagues was published in the Journal of Clinical Oncology. In this study in adults, which is who I primarily deal with, they randomized a group of 270 patients to 3 treatment groups. All these patients had intermediate to high risk for developing tumor lysis syndrome. To be eligible they had to be over age 18, have intermediate or high risk, and generally have some features we talked about earlier, which made them at risk for developing tumor lysis syndrome. This could be bulky disease or a high LDH [lactate dehydrogenase], which is indicative of a high proliferative rate.

There were 3 arms. Arm 1 was rasburicase alone, which was given for 5 days. Arm 2 was the combination of rasburicase and allopurinol. Rasburicase was given on days 1, 2, and 3. Allopurinol was given on days 3, 4, and 5. So it was an overlap on day 3. The third group was using allopurinol alone, and it was given for 5 consecutive days. All the patients were supposed to get hydration. It was left to the investigators’ institutional guidelines for how to do hydration.

But they generally recommended 2 to 3 L of normal saline per day. About 98% of the patients on the 3 arms got this aggressive hydration. Very few patients didn’t get aggressive hydration. The primary end point was to see if they could maintain uric acid levels at normal levels if they were already at a normal level. Coming back to that description of between 4 and 8 mg/dL, they actually wanted it less than 7.5 mg/dL and, depending how long could they maintain a uric acid level, less than 7.5 mg/dL.

I think 10% to 15% of patients had presented with high uric acid levels already, over 8 mg/dL, and they wanted to look at how quickly uric acid levels would come down with these 3 treatment arms. The study demonstrated that the patients who got some form of rasburicase did better than the patients who got allopurinol alone in terms of maintaining relatively normal uric acid levels and bringing down uric acid levels.

The most superior arm in regard to this was the rasburicase alone arm. There was nonsignificant improvement with the use of rasburicase and allopurinol in terms of keeping down. Still, there was a very clear trend that giving allopurinol and rasburicase together in that sequence that I described was better than just giving allopurinol alone.

It was not powered to look to see how much it prevented clinical tumor lysis syndrome, and specifically renal failure. But there was a slight trend that there were fewer renal complications and those patients who got rasburicase again. But it was not statistically significant, and the study was not powered to do so, which is always a question that I get from oncologists. Well, did it prevent tumor lysis syndrome?

From a laboratory perspective, it seemed to—the data would indicate that it was better on the rasburicase arm. But in terms of clinical tumor lysis syndrome, it was not powered to do so, nor was anything significant even using an underpowered population.

Transcript Edited for Clarity