5FU CARDIOTOXICITY

NEW YORK (Reuters Health) Nov 18 - The cancer drug fluorouracil causes cardiotoxicity in slightly less than one in 10 patients, according to a study published online November 15th in the Journal of Clinical Oncology.

Though angina was relatively common, the cardiotoxic effects of fluorouracil (FU) reversed and none of the patients with angina in the study had proven myocardial infarction, the authors report.

Previous studies have shown that between 1% and 18% of patients on FU-based chemotherapy regimens develop cardiotoxicity; however, most of the references in the medical literature to serious cardiac adverse events have been case reports.

"Subclinical cardiac influence from FU is a frequent phenomenon without long-term impairment of function," write the investigators, led by Dr. S�ren Astrup Jensen of the University of Copenhagen, Denmark.

The study group included 106 consecutive stage II-IV colorectal cancer patients, all of whom received the adjuvant FOLFOX4 chemotherapy regimen, the most recent version of oxaliplatin, leucovorin, and 5-FU combination therapy.

The main outcome measures were cardiotoxicity grade 2 or 3, as measured by the Common Toxicity Criteria (CTC), and levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and lactic acid. NT-proBNP levels in the plasma increase as the left ventricle begins to dysfunction; lactic acid signals a shift in the heart to anaerobic metabolism.

Patients were assessed for adverse cardiac events and cardiotoxicity before chemotherapy, during FU therapy, and 2 weeks after the 12-week course of chemotherapy was completed.

Nine patients (8.5%) had symptoms of FU-induced cardiotoxicity, none of which resulted in proven myocardial infarction. For seven patients, angina occurred at rest, with the other two cases occurring during workload.

Lactic acid levels weren't changed significantly. NT-proBNP did significantly increase (P<.001) from baseline -- 14.5 pmol/L to 28.3 pmol/L during FU therapy -- but it reverted to 11.3 pmol/L at follow-up.

However, NT-proBNP levels were much higher in the subset of patients with cardiotoxicity, rising to 55.3 pmol/L, a level significantly higher than the 25.4 pmol/L in patients with no symptoms (P<.001).

It's still not obvious from these results that NT-proBNP should be used immediately as a biomarker for cardiotoxicity in patients receiving FU-based chemotherapy regimens.

"Whether the NT-proBNP level following the full FU dose of the first treatment course is an accurate predictor for impending cardiotoxicity remains to be clarified," the investigators conclude.