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Chemotherapy of Breast Cancer

Can We Improve Outcome and Decrease Toxicity by Tailoring Therapy?

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American Journal of Cancer

Abstract

Standard adjuvant polychemotherapy for patients with breast cancer significantly improves their survival and is used for this patient group worldwide. In the beginning of this era, mainly CMF (cyclophosphamide, methotrexate and fluorouracil) was used but CMF is nowadays often replaced by anthracycline containing regimens after results favoring anthracyclines were published. The role of taxanes in the adjuvant setting is not yet fully understood; however, this should become clearer following the results from several ongoing randomized studies. In addition to the question of which drugs to use, dosage recommendations are a more complex issue. Low dosage regimens have been associated with inferior survival results compared with standard dosages in the adjuvant setting. High dosage regimens of anthracyclines have not been associated with better survival in some studies, although some investigators have shown the opposite. The use of very high doses requiring autologous bone marrow support have not resulted in survival gains in randomized studies.

The body surface area (BSA) method is used to calculate doses. This method fails to standardize the marked interpatient variation in pharmacokinetics for most cytotoxic drugs. BSA is not correlated to hepatic function. Hepatic function varies widely among different persons and most drugs are excreted through the liver, which is one of the reasons for the difference in toxicity among different people. When patients experience toxicity from chemotherapy, a dose reduction is considered but when patients experience no toxicity the dose is seldom increased. It has been shown that patients treated with adjuvant chemotherapy doses causing a low leukocyte nadir have significantly better disease free survival and overall survival than those with higher nadir.

One way to treat patients with breast cancer in the adjuvant setting is to use the tailored regimen described in this article. The aim of this regimen is to produce similar hematological toxicity for all patients and to achieve this the patients are treated at six different dose levels. This tailored treatment regimen has shown significantly better 3-year relapse-free survival than high dose treatment combined with autologous stem cell transplantation. Many facts support the idea of tailored treatment as being more effective than standard doses calculated with the help of BSA. An ongoing study is comparing standard FEC (fluorouracil, epirubicin, cyclophosphamide) with tailored FEC. This study will hopefully contribute to the knowledge on how to give chemotherapy in the most optimal way.

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Acknowledgements

All patients and collaborators in the SB69401 study are acknowledged. Supported in part by grants from Nordic Cancer Union and the Swedish Cancer Society.

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  1. Radiumhemmet, Karolinska Institute and Hospital, Stockholm, SE-171 76, Sweden

    Elisabet Lidbrink & Jonas Bergh

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  1. Elisabet Lidbrink
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Correspondence to Elisabet Lidbrink.

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Lidbrink, E., Bergh, J. Chemotherapy of Breast Cancer. Am J Cancer 1, 165–171 (2002). https://doi.org/10.2165/00024669-200201030-00001

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