1University Hospital Gasthuisberg, Leuven, Belgium (E-mail: eric.vancutsem@uz.kuleuven.ac.be); 2Centro Paulista de Oncologia, Albert Einstein Hospital, Sâo Paulo, Brazil; 3Baylor-Charles A. Sammons Cancer Center, US Oncology, Dallas, Texas, USA; 4Biostatistics, F. Hoffmann-La Roche Ltd, Basel, Switzerland; 5Clinical Science, F. Hoffmann-La Roche Ltd, Basel, Switzerland (E-mail: eric.vancutsem@uz.kuleuven.ac.be)
Acute cardiotoxicity has recently been reported in two patients receiving capecitabine [1, 2], an oral fluoropyrimidine that undergoes a three-step enzymatic conversion to 5-fluorouracil (5-FU). Cardiotoxicity due to 5-FU is a rare but serious side effect, reported in 118% of patients [3]. The most common symptom of fluorouracil-associated cardiotoxicity is angina-like chest pain [3]. Less common symptoms include cardiac arrythmias, congestive heart failure, myocardial infarction, dilatative cardiomyopathy, cardiogenic shock, cardiac arrest or sudden death syndrome. The mechanism of 5-FU-induced cardiotoxicity has not been completely elucidated. Most cases occur during or following initial courses of fluorouracil treatment and are generally reversible on treatment discontinuation. Only a proportion (18%) of patients developing cardiotoxicity following 5-FU exposure have a history of underlying cardiac disease.
To enable a direct comparison between the incidence of cardiotoxic events in patients receiving capecitabine monotherapy (1250 mg/m2 twice daily, days 114, followed by a 7-day rest period) and i.v. 5-FU/LV (Mayo Clinic regimen), a retrospective analysis was performed on two randomized phase III studies comparing the two regimens as first-line therapy for patients with metastatic colorectal cancer (MCRC) (n = 1189) [4, 5]. Two large phase II studies evaluating capecitabine monotherapy in patients with taxane-pretreated metastatic breast cancer (MBC) (n = 236) [6, 7] were also analyzed. This analysis revealed a similar low incidence (3%) of capecitabine-related cardiotoxic events in patients with MCRC and MBC (Table 1).
|
In conclusion, these data show that the incidence of cardiotoxicity in patients receiving capecitabine monotherapy is within the range that occurs with 5-FU. Physicians administering any fluoropyrimidine should be aware of the potential for cardiotoxicity and discontinue treatment promptly in patients developing clinical signs of such toxicity.
E. Van Cutse m1, P. M. Hoff2, J. L. Blum3, M. Abt4 & B. Osterwalder5
1University Hospital Gasthuisberg, Leuven, Belgium (E-mail: eric.vancutsem@uz.kuleuven.ac.be); 2Centro Paulista de Oncologia, Albert Einstein Hospital, Sâo Paulo, Brazil; 3Baylor-Charles A. Sammons Cancer Center, US Oncology, Dallas, Texas, USA; 4Biostatistics, F. Hoffmann-La Roche Ltd, Basel, Switzerland; 5Clinical Science, F. Hoffmann-La Roche Ltd, Basel, Switzerland (E-mail: Eric.VanCutsem@uz.kuleuven.ac.be)
References
1. Schnetzler B, Popova N, Collao Lamb C et al. Coronary spasm induced by capecitabine. Ann Oncol 2001; 12: 723725.[ISI][Medline]
2. Bertolini A, Fiumano M, Fusco O et al. Acute cardiotoxicity during capecitabine treatment: a case report. Tumori 2001; 87: 200206.[ISI][Medline]
3. Becker K, Erckenbrecht JF, Haussinger D et al. Cardiotoxicity of the antiproliferative compound fluorouracil. Drugs 1999; 57: 475484.[ISI][Medline]
4.
Hoff PM, Ansari R, Batist G et al. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol 2001; 19: 22822292.
5.
Van Cutsem E, Twelves C, Cassidy J et al. Oral capecitabine compared with intravenous fluorouracil plus leucovorin (Mayo Clinic regimen) in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol 2001; 19: 40934096.
6.
Blum JL, Jones SE, Buzdar AU et al. Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer. J Clin Oncol 1999; 17: 485493.
7. Blum JL, Dieras V, La Russo PM et al. Multicenter, phase II study of capecitabine in taxane-pretreated metastatic breast cancer patients. Cancer 2001; 92: 17591768.[ISI][Medline]