Pheochromocytoma Surgery Pretreatments Both 'Quite Good'

Miriam E Tucker

March 18, 2018

CHICAGO, Illinois — Phenoxybenzamine and doxazosin pretreatments are equally effective in maintaining hemodynamic control during surgical resection of pheochromocytoma, new data suggest. 

The Preoperative Treatment of Patients With a Pheochromocytoma (PRESCRIPT) study is the first randomized controlled trial comparing the efficacy of the competitive alpha-1 antagonist doxazosin to the noncompetitive alpha1-/alpha-2 antagonist phenoxybenzamine.

Preliminary study results were presented here on March 17 at ENDO 2018: The Endocrine Society Annual Meeting by Edward Buitenwerf, MD, of University Medical Center Groningen, the Netherlands.

"For the primary endpoint, we didn't find a difference in the intraoperative hemodynamics between the two drugs. In secondary endpoints, we did see that in the phenoxybenzamine group there was less hypertension during surgery. That's one of the things you try to prevent. So, on secondary endpoints there might be a slight advantage of phenoxybenzamine, but overall there's not a large difference between the drugs. Both of them are quite good," Buitenwerf told Medscape Medical News

Asked to comment, session moderator Gail K Adler, MD, PhD, told Medscape Medical News that when doxazosin first became available, people assumed it would provide better hemodynamic control than phenoxybenzamine because it's longer acting. That hasn't appeared to be the case, although compliance might be a bit better with the less-frequent dosing.

"There had never been a head-to-head trial, so this is really nice information that both can be used...I think if you're just aware of what the differences might be, you can handle them," said Adler, who is associate professor of medicine at Brigham and Women's Hospital, Boston, Massachusetts.

No Difference in Primary Endpoint, but Cost May Guide Decision

Pheochromocytomas are neuroendocrine tumors arising from the adrenal medulla. The average age at diagnosis is 25 years in patients with hereditary pheochromocytoma, which comprises around 25% of all cases, and 44 years in those with sporadic disease.

Although pheochromocytomas are rare, diagnosis is critical because the malignancy rate is 10%, and in those with malignant pheochromocytomas, the 5-year survival rate is less than 50%. For those with benign pheochromocytomas, however, the 5-year survival rate is greater than 95%.

Many patients present with spells that include hypertension, headaches, sweating, palpitations, and tremors. However, about 50% of patients with pheochromocytoma are asymptomatic, with the disease found incidentally during, for example, abdominal imaging for unrelated reasons.

Alpha-adrenergic blockade should commence at diagnosis, with preoperative maximization to avoid potentially fatal cardiovascular complications, such as hypertensive crisis, arrhythmia, myocardial infarction, and pulmonary edema. Such complications can result from excess catecholamine secretion during surgery.

In the PRESCRIPT trial, 134 adults with benign pheochromocytoma were randomized to 14 days of presurgical treatment with phenoxybenzamine 120 mg/day or doxazosin 40 mg/day. Preoperative blood pressure targets were less than 130/80mmHg (supine) and systolic 90 to 110 mmHg (upright). Beta-blockers were added if heart rate exceeded 80 bpm/min (supine) or 100 bpm/min (upright).

The primary endpoint, intraoperative time outside the blood pressure target range, was 12% with doxazosin, which was not significantly different from the 11% with phenoxybenzamine (P = .75).

However, time spent with systolic blood pressure above 160 mmHg was lower with phenoxybenzamine (P = .005). Preoperative beta-receptor agonist use was 89% with phenoxybenzamine vs 66% with doxazosin (P = .002), presumably because of greater reflex tachycardia, said Buitenwerf. 

On the other hand, those pretreated with phenoxybenzamine were less likely to require intraoperative vasodilating agents compared with doxazosin (55% vs 79%, P = .02).

Magnesium sulfate was not used intraoperatively in the phenoxybenzamine-treated patients, while a cumulative dose of 3 grams was used in the doxazosin-treated patients (P = .005).

Use of intraoperatively administered inotropic/vasopressive agents and intravenous phenylephrine and norepinephrine did not differ significantly between groups.

One audience member from the United States noted that cost is an issue, as phenoxybenzamine is far more expensive than doxazosin, even though both drugs are generic.   

The investigators haven't yet analyzed the data by patient subgroups, but they plan to do that next, Buitenwerf told Medscape Medical News.

"We can use the PRESCRIPT data to identify predictors of instability, or which patients need which drug to get a more individual approach."

The study was funded by an unrestricted grant from Ipsen. Buitenwerf reported no other relevant financial relationships.

ENDO 2018. March 17, 2018; Chicago, Illinois. Abstract OR09-1

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