Analysis of dose intensity for chemotherapy in early (stage II) and advanced breast cancer

In chemotherapy of advanced breast cancer, the dose intensities of regimens containing cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) and cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) correlate with remission rate. The correlation is even better if dose intensity is calculated from doses actually given instead of from targeted doses. Also, in adjuvant chemotherapy of stage II breast cancer, the dose intensities of CMF-containing regimens correlate with relapse-free survival. The adjuvant trials analyzed included studies containing only 1 or 2 of C, M, or F or with L-phenylalanine mustard (melphalan) instead of C. Three-year relapse-free survival was clearly related to dose intensity whether the analysis was of trials containing all 4 prognostic groups [women less than 50 yr with 1-3 and greater than 3 positive nodes; and those greater than or equal to 50 yr with 1-3 and greater than 3 positive nodes (P less than .00001)] or of trials in which each of these 4 groups were analyzed separately (P less than .005). In multivariate analysis, dose intensity correlated with relapse-free survival (P less than .00001), independent of the number of positive nodes or menopausal status. Randomized trials will be required before we can determine if prospective increases of dose intensity will improve outcome of chemotherapy in breast cancer.