The Pharmaceutical Journal
Vol 275 No 7369 p398
1 October 2005

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Reducing doses in obese breast cancer patients worsens outcomes

Reducing chemotherapy doses for obese breast cancer patients who have endocrine non-responsive disease is associated with worse outcomes, a study has shown (Lancet 2005;366:1108).

Chemotherapy doses for obese patients are often reduced, because of concerns about overdosing. The study of 2,140 premenopausal women with node-positive breast cancer receiving adjuvant cyclophosphamide, methotrexate and 5-fluorouracil showed that 39 per cent of obese patients were given doses in their first chemotherapy course below 85 per cent of the expected dose, compared with 16 per cent of those with normal or intermediate body-mass index. These lower doses were associated with worse rates of disease-free and overall survival for both obese and non-obese patients with low or no oestrogen-receptor expression (ER-low or ER-absent) tumours, with a hazard ratio of 0.68 (95 per cent confidence interval 0.54–0.86) for disease-free survival and 0.72 (0.56–0.94) for overall survival.
However, for patients with higher oestrogen-receptor expression (ER-positive) tumours lower doses were not associated with reduced survival rates.

“Our results indicate that, for patients with endocrine non-responsive disease (ER-absent and ER-low tumour), a reduced dose during the first course of chemotherapy is detrimental,” the authors say. Therefore, they argue, “a priori reduction in the chemotherapy dose for these patients should be avoided”.

Andrew Stanley, network pharmacist for the Pan-Birmingham Cancer Network, commented: “The article reawakens the old question of whether you should dose on actual body surface or corrected surface area and whether you should correct for purely weight or whether you should use body mass index.” He said the study also raises the issue of how frequently surface area and, therefore, dose should be recalculated. Mr Stanley added that the study illustrates the importance of aggressive dosing schedules in adjuvant patients, for whom the intention is to cure. “Perhaps we should therefore differentiate between adjuvant, potentially curative patients and those receiving chemotherapy in a palliative or symptom-relief context,” he suggests.