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DOSE-RESPONSE TO ADJUVANT CHEMOTHERAPY IN BREAST CANCER.

When doses of adjuvant chemotherapeutic drugs for breast cancer are lowered to minimize toxicity, is efficacy compromised? The answer, according to this study, appears to be yes.

After undergoing surgery, 1572 women with node-positive breast cancer but no distant metastases were randomized to one of three regimens that included cyclophosphamide, doxorubicin, and fluorouracil: a high-dose, high-intensity regimen given over 4 months, the same total dose given over 6 months, and a 4-month low-dose regimen. After a median of 3.4 years, the two high-dose groups had significantly better disease-free and overall survival than the low-dose group; the high-dose, high-intensity group had an absolute increase in actuarial disease-free and overall survival of roughly 10 percent as compared to the low-dose group. Although high- dose, high-intensity chemotherapy was more toxic than the other regimens, there were only two treatment-related deaths in the study as a whole.

A second article used data from 442 of these patients to examine whether molecular tumor markers predict the efficacy of high-dose chemotherapy. When tumors expressed high levels of the oncogene c-erbB-2, patients in the high-dose, high- intensity chemotherapy group had significantly better disease-free and overall survival than those in the other two groups. But when tumors had low c-erbB-2 expression, the intensity of chemotherapy did not affect survival.

Comment: An editorial concludes that this study "establishes beyond any doubt" the superiority of high-dose adjuvant chemotherapy, at least for the combination of drugs used in the trial. However, the use of molecular markers to predict response to chemotherapy is still largely experimental; their use in routine clinical practice requires further study.

— AS Brett

Published in Journal Watch General Medicine May 20, 1994

Citation(s):

Goldhirsch A; Gelber RD. Understanding adjuvant chemotherapy for breast cancer. N Engl J Med 1994 May 5 330 1308-1309.

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Muss HB et al. c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med 1994 May 5 330 1260-1266.

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Wood WC et al. Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma. N Engl J Med 1994 May 5 330 1253-1259.

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