The Pharmaceutical Journal
Vol 276 No 7390 p259
4 March 2006

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Trastuzumab regimen preserves cardiac function

Adjuvant treatment with docetaxel (Taxotere), compared with vinorelbine (Navelbine), improves recurrence-free survival in women with early breast cancer, say researchers (New England Journal of Medicine 2006;354:809). In addition, a short course of trastuzumab (Herceptin), administered concomitantly, is beneficial in women with HER2-positive breast cancer and appears to have minimal cardiac side effects.

The researchers randomised 1,010 women with breast cancer to receive three cycles of docetaxel or vinorelbine followed by three cycles of fluorouracil, epirubicin and cyclophosphamide (FEC). Women with HER2-positive breast cancer were further randomised to receive or not to receive nine weekly infusions of trastuzumab.

Trastuzumab was administered before other cardiotoxic therapies and concomitantly with potentially synergistic chemotherapy — but for only nine weeks — to test the hypothesis that such a schedule would limit cardiotoxicity and maintain efficacy, say the researchers.

Recurrence-free survival at three years was higher in the docetaxel than in the vinorelbine group (91 per cent versus 86 per cent; hazard ratio 0.58; 95 per cent confidence interval 0.40–0.85; P=0.005). Development of distant metastases was also less common in the docetaxel group (P=0.008), however, overall survival was not significantly different between the two groups. Docetaxel was associated with more adverse effects than was vinorelbine — 36.9 per cent in the docetaxel group developed neutropenic fever which necessitated a reduction in its starting dose during the study (from 100mg/m² to 80mg/m²).

Among the women with HER2-positive breast cancer, those who received trastuzumab had better three-year recurrence-free survival than those who did not (89 per cent versus 78 per cent; hazard ratio 0.42; 95 per cent confidence interval 0.21–0.83; P=0.01). They also had fewer distant recurrences of cancer (P=0.002) and overall survival tended to be better (P=0.07). None of the tarstuzumab-treated women had cardiac failure, said the researchers. They added that, unexpectedly, these women had slightly better maintenance of left ventricular ejection fraction than those who did not receive trastuzumab. They suggested that administration of trastuzumab before FEC and radiotherapy as well as the small cumulative dose of epirubicin may have contributed to the preservation of cardiac function.

The author of an accompanying editorial (ibid, p789), commented: “The study by Joensuu et al demonstrates that trastuzumab can be given in therapeutically active doses with negligible cardiac side effects, but whether a similar result might hold in larger numbers of patients or in women with preexisting heart disease is now a pressing question.”