With the combination of careful cardiac monitoring, calcium channel blockers and long-acting oral nitrates, researchers at the Hospital of the University of Pennsylvania were able to successfully rechallenge with fluoropyrimidines agents such as 5-FU and capecitabine in patients who experienced cardiac toxicity related to the chemotherapy.
Suparna C. Clasen, MD, presented results from the case series Tuesday in an abstract poster session.
“Fluoropyrimidines are the backbone of standard chemotherapy for gastrointestinal and other major solid malignancies,” said Clasen, a fellow at the Hospital of the University of Pennsylvania in Philadelphia.
However, fluoropyrimidines use has been limited by cardiac toxicity, presenting as a spectrum of asymptomatic and symptomatic manifestations related to coronary vasospasm leading to myocardial ischemia. Clasen said experiencing these serious adverse effects has rightfully made patients and clinicians leery to reintroduce these medications.
Clasen and colleagues reported a case series of 11 consecutive patients with suspected fluoropyrimidine-induced coronary vasospasm who were successfully rechallenged to allow for chemotherapy completion.
Together with Joseph R. Carver, MD, Clasen developed two algorithms for rechallenge that varied by the type of fluoropyrimidines given, either oral or by infusion. Patients underwent a full work-up to test for underlying coronary artery disease and to try to modify underlying cardiovascular risk factors such as diabetes or hypertension.
“We never take it for granted that it is coronary vasospasm,” Clasen said. “We want to rule out underlying coronary artery disease that is the culprit for the chest pain presentation and, if CAD is present, understand how much is underlying burden prior to rechallenge.”
The protocols use a bolus infusion regimen of intravenous 5-FU chemotherapy and oral capecitabine with cardioprotective pretreatment of two calcium blockers and long-acting oral nitrates, which are titrated to the patient’s blood pressure and heart rate.
“We pretreat with anti-anginal agents before infusion, treat during infusion, and after the infusion for up to 24 hours after the first dose,” Clasen said. “Patients are then closely observed either in an inpatient setting if considered high-risk or in an outpatient setting where they are closely monitored.”
All of the patients in the cohort successfully continued and completed their previously planned first-line fluoropyrimidine chemotherapy regimen with minimal therapeutic interruption. There were no cardiac events or evidence of recurrent coronary spasm after completion of therapy. Prophylactic medications were discontinued upon therapy completion.
In the case series, Clasen and colleagues took all comers presenting to the cardio-oncology clinic with suspected fluoropyrimidine-related cardiotoxicity, but future research might attempt to identify if there are certain patients with an underlying genotype that makes them more susceptible to vasospasm.
“We think this is a protocol that could potentially be widely implemented with the inclusion of very careful cardiac monitoring,” Clasen said. “This has the potential to reintroduce a widely used and potentially curative chemotherapy agent for these patients.”