Dosage parameters in chemotherapy of breast cancer.
The concept of dose intensity provides a starting point for studying dose-response relationships. The summation dose intensity method (SDI) is an improvement over previous methods of calculating dose intensity because it accounts for differences in drug activity and allows the dose intensity of combinations containing the different drugs to be compared on one scale. It may also ultimately prove useful in defining the contribution of cumulative dose and dose size. Results from initial randomized trials testing dose intensification in breast cancer suggested but did not confirm its importance because dose size and cumulative dose were usually increased concurrently. Results from several recent trials in which dose intensity was increased while cumulative dose was held constant suggest that dose intensity may not be pre-eminent, but that both dosage parameters affect outcome. In addition, there may be a threshold dose intensity that must be exceeded before treatment causes tumor regression. From both retrospective analyses and prospective trials of adjuvant chemotherapy, it is clear that the subsets of patients who benefit most from dosage increases are those with poor prognostic factors. Larger dose sizes contribute more toxicity but, within the conventional range, probably contribute little independent therapeutic benefit. In contrast, reduced size doses of non-antimetabolites given at very short intervals may reduce acute toxicity, maintain dose intensity above threshold, and allow delivery of larger cumulative amounts of chemotherapy. This dose dense strategy may produce results superior to the use of fewer but larger doses.
Hryniuk
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Wayne State University, Karmanos Cancer Institute, 4th Floor Hudson-Webber, Cancer Research Center, 4100 John R., Detroit, MI 48201, USA.