Article Text

Docetaxel induced cardiotoxicity
  1. MASAKI SHIMOYAMA,
  2. YOKO MURATA*,
  3. KEN-ICHI SUMI*,
  4. RYUICHI HAMAZOE*,
  5. ISSEI KOMURO
  1. Departments of Cardiovascular Medicine, and Surgery *
  2. Philanthropic Hospital of Yonago
  3. Yonago, Japan
  4. Third Department of Medicine
  5. Graduate School of Medicine
  6. Chiba University
  7. Chiba, Japan
  1. Dr Masaki Shimoyama, Division of Cardiology, Department of Medicine I, Tottori University, Faculty of Medicine, 36-1 Nishi-machi, Yonago 683-8504, Japan;masaki-tky{at}umin.ac.jp

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Docetaxel is a new taxoid antineoplastic agent.1 2Its mechanism of action is primarily related to its ability to enhance microtubule assembly and to stabilise microtubules by preventing their depolymerisation, thus disrupting normal cell division.2Since docetaxel has significant cytotoxic activity against human breast cancer in vitro and in vivo, it is widely used to treat patients with breast cancer, especially those with metastatic breast cancer. It has been shown that increased microtubule density, for which microtubule stabilisation is one potential mechanism, causes contractile dysfunction in cardiac hypertrophy.3 Since docetaxel exerts its actions by stabilising microtubules, it is reasonable to consider that docetaxel may induce contractile dysfunction as a cardiotoxic agent. Thus, we examined the effect of docetaxel on cardiac function and the serum concentration of cardiac neurohormones one day before, one day after, and three weeks after docetaxel administration.

Ten consecutive patients with breast cancer having skin metastasis who received docetaxel were investigated. All patients were women and their mean (SEM) age was 51.8 (2.5) years. Docetaxel dissolved into 500 ml of 0.9% saline solution was administered with an intravenous drip injection for three hours. The mean dosage of docetaxel was 52.36 (6.35) mg/m2. Although the serum concentration of brain natriuretic peptide (BNP) was within normal range before treatment, it was significantly raised on the day after docetaxel administration (table 1). In contrast, concentrations of other circulating cardiac neurohormones (atrial natriuretic peptide, renin, aldosterone, noradrenaline (norepinephrine), and adrenaline (epinephrine)) were within the normal range at both determinative points (table 1). Additionally, blood pressure was not affected by this treatment (one day before chemotherapy 126 (7)/74 (6) mm Hg; one day after chemotherapy 123 (8)/76 (8) mm Hg; three weeks after chemotherapy 127 (5)/69 (9) mm Hg; NS). To assess left ventricular systolic and diastolic functions, we measured fractional shortening, ejection fraction, mitral inflow E:A ratio, and deceleration time by echocardiography. While fractional shortening and ejection fraction were not affected by docetaxel, the E:A ratio was significantly decreased and deceleration time was significantly increased (table 1). Additionally, the maximum diameter of inferior vena cava was not affected by this treatment. These results suggest that docetaxel induced left ventricular diastolic dysfunction and an increase in serum BNP concentration without increasing preload or afterload.

Table 1

Serial changes in biochemical and echocardiographic parameters

BNP is a useful biochemical marker of left ventricular dysfunction, having diagnostic, therapeutic, and prognostic implications.4 In addition, diastolic dysfunction is well known as a cause of congestive heart failure.5 In this study, the increase in BNP concentration, the decrease in E:A ratio, and the increase in deceleration time were transient and returned to baseline within three weeks in all patients (table 1). However, since docetaxel induced the transient abnormalities of the serum BNP concentration, E:A ratio, and deceleration time, even in patients with normal cardiac function, it is possible that this agent may induce heart failure in patients with left ventricular dysfunction. Consequently, it is advisable to check the cardiac function of patients to be treated with docetaxel by echocardiography. In addition, serum BNP can be a useful marker by which to evaluate docetaxel induced cardiotoxicity.

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