Dose Intensity in Chemotherapy

Abstract

To the Editor: In a recent article, Hryniuk and Bush have established a strong correlation between dose intensity of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy, and the rate of tumor response in patients with metastatic breast cancer. They also observed a significant correlation between rate of tumor response and median survival time (r = .66, P < .001). The authors were careful to avoid the conclusion that there was a direct correlation between dose intensity and median survival, but it is surprising that they did not examine this more important relationship directly. We have used data provided in their paper to test for correlation between median survival time and dose intensity for patients receiving CMF chemotherapy, and find little evidence for a direct relationship (r = .25, P = .27—two-tailed Student's t test). Moreover, if the studies are weighted according to the number of patients in them, the correlation coefficient is even lower (r = .14, P = .50—two-tailed Student's t test). Unfortunately, metastatic breast cancer is not cured by chemotherapy, and appropriate endpoints are those of palliation, namely quantity and quality of survival. Quality of survival cannot easily be addressed in a retrospective review, but increasing dose intensity has the capability both to improve quality of life by ameliorating symptoms of disease, and to decrease it by adding toxicity. Factors such as sites of metastases and performance status of patients are known to influence duration of survival and could mask a relationship with dose intensity. However, the data reviewed by Hryniuk and Bush do not provide evidence for a relationship between dose of chemotherapy and survival. A prospective randomized trial is in progress at our institution that addresses the relationship between dose intensity of CMF chemotherapy and both quantity and quality of survival for patients with metastatic breast cancer. In the absence of results from this and other prospective trials that address the dose-response effect of chemotherapy in palliation, one should not assume that more is better.