Dose and Dose Intensity as Determinants of Outcome in the Adjuvant Treatment of Breast Cancer

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Abstract
Background: Both total dose and dose intensity of adjuvant chemotherapy are postulated to be important variables in the outcome for patients with operable breast cancer. The Cancer and Leukemia Group B study 8541 examined the effects of adjuvant treatment using conventional-range dose and dose intensity in female patients with stage II (axillary lymph node-positive) breast cancer. Methods: Within 6 weeks of surgery (radical mastectomy, modified radical mastectomy, or lumpectomy), 1550 patients with unilateral breast cancer were randomly assigned to one of three treatment arms: high-, moderate-, or low-dose intensity. The patients received cyclophosphamide, doxorubicin, and 5- fluorouracil on day 1 of each chemotherapy cycle, with 5- fluorouracil administration repeated on day 8. The highdose arm had twice the dose intensity and twice the drug dose as the low-dose arm. The moderate-dose arm had two thirds the dose intensity as the high-dose arm but the same total drug dose. Disease-free survival and overall survival were primary end points of the study. Results: At a median follow-up of 9 years, disease-free survival and overall survival for patients on the moderate- and high-dose arms are superior to the corresponding survival measures for patients on the low-dose arm (two-sided P<.0001 and two-sided P = .004, respectively), with no difference in disease-free or overall survival between the moderate- and the high-dose arms. At 5 years, overall survival (average ± standard error) is 79% ± 2% for patients on the high-dose arm, 77% ± 2% for the patients on the moderate-dose arm, and 72% ± 2% for patients on the low-dose arm; disease-free survival is 66% ± 2%, 61% ± 2%, and 56% ± 2%, respectively. Conclusion: Within the conventional dose range for this chemotherapy regimen, a higher dose is associated with better disease-free survival and overall survival. [J Natl Cancer Inst 1998;90: 1205–11]