Cardiotoxicity from Capecitabine Chemotherapy: Prospective Study of Incidence at Rest and During Physical Exercise.

BACKGROUND: Physical activity may increase the risk of cardiotoxicity (myocardial ischemia, major arrhythmias) of 5-Fluorouracil, but this risk has never been investigated for its prodrug capecitabine. PATIENTS AND METHODS: One hundred and ninety-two consecutive patients undergoing capecitabine chemotherapy from December 1, 2010 through July 31, 2016 were prospectively evaluated. The baseline evaluation included electrocardiography (ECG) and echocardiography (2DE); a follow-up evaluation, including ECG and exercise stress testing (2DE in case of ECG abnormalities), was done after ≥10 days of treatment. Cardiotoxicity was suspected from ischemic ECG changes, new kinetic abnormalities at 2DE, Lown classification ≥2 ventricular arrhythmia, symptomatic arrhythmias, or positive stress test, and confirmed by a negative stress test after capecitabine washout. RESULTS: Cardiotoxicity was diagnosed in 32 patients (16.7%): six at rest and 26 during exercise. All 32 patients had ECG abnormalities: ST-segment changes (24 patients), negative T-waves (2) and/or arrhythmias: ventricular arrhythmias (14 cases), supraventricular tachycardia (2), complete heart block (1). Eight patients had typical symptoms, 6 had atypical symptoms, 1 had syncope, 17 (53%) were asymptomatic. Cardiotoxicity was more common in patients with atypical symptoms during daily life (OR = 15.7) and in those on a therapeutic schedule of 5 days/week (OR = 9.44). CONCLUSION: Capecitabine cardiotoxicity is frequent, and often elicited by physical effort. Oncologists, cardiologists, and general practitioners should be aware of this risk. Active cardiotoxicity surveillance with ECG (and echocardiogram and/or stress testing in suspected cases) during therapy is recommended. CLINICAL TRIALS REGISTRATION NUMBER: CRO-2010-17.

Neoplastic pericardial disease in lung cancer: impact on outcomes of different treatment strategies. A multicenter study.

BACKGROUND: Local (intrapericardial) chemotherapy has been reported to be useful for the treatment of neoplastic pericardial disease, but it has never been compared to systemic chemotherapy, a combination of the two and simple pericardial drainage or sclerosis. METHODS: We analyzed the clinical and echocardiographic data of 119 patients, suffering of neoplastic pericarditis due to lung cancer (97 with non-small-cell), comparing the outcomes of four different treatment strategies (extended catheter drainage/sclerosis, systemic chemotherapy, local chemotherapy, and combined - local plus systemic - chemotherapy) at the last available follow-up or at the change of therapy after a treatment failure. The outcomes (based on semiquantitative evaluation of pericardial disease) were classified as complete, partial, no response and progressing disease. RESULTS: A complete response was achieved in 37/53 of patients with combined, in 12/22 with local, in 5/27 with systemic chemotherapy, respectively, and in 4/17 after drainage/sclerosis (p<0.001). Overall response was achieved in 51/53 with combined, 18/22 and 16/27 with local or systemic chemotherapy, respectively, and in 5/17 with drainage/sclerosis only (p<0.001). Survival was significantly better after combined chemotherapy (p<0.001) and 12/53 patients (23%) in this subgroup survived more than 1 year. The overall response rate was higher with intrapericardial cisplatinum than with other agents (98% vs 80%, χ(2)=7.69, p<0.01). CONCLUSIONS: Local chemotherapy, alone or with systemic chemotherapy, is effective in treating pericardial metastases from lung carcinoma, leading to a good control of pericardial effusion in 92% of cases, and to complete disappearance of effusion and masses in 65%. Combined therapy is significantly better than any other treatment. Pericardiocentesis and intrapericardial chemotherapy should be used whenever possible in lung cancer neoplastic pericardial disease, not only in case of tamponade.

Severe ventricular dysrhythmias and silent ischemia during infusion of the antimetabolite 5-fluorouracil and cis-platin.

The antimetabolite 5-fluorouracil is frequently used in the therapy of various malignancies. Cardiotoxicity has frequently been described during treatment, but there is no common agreement on the need to perform cardiovascular monitoring of patients during 5-fluorouracil administration. We report the case of a young patient with an head-neck cancer on whom a continuous electrocardiogram recording was performed, documenting serious ventricular dysrhythmias in the presence of myocardial ischemia during 5-fluorouracil and cis-platin infusion.