Is high-dose chemotherapy dead?

Abstract

The story of high-dose chemotherapy in breast cancer is a remarkable one and it contains a number of valuable lessons for all of us. Many oncologists believe that this story has come to an end and that the further study of this treatment modality is no longer worthwhile. However, such a belief could be just as premature and thoughtless as the uncritical use of high-dose chemotherapy that was so common 10 years ago. Small phase I and II studies in the 1980s had shown that high-dose chemotherapy in advanced breast cancer was associated with unusually high complete response rates, and that long-term disease-free survival was observed in a proportion of patients [1]. Similar findings were reported from the American and European bone marrow transplant registries. Approximately 20% of patients with stage IV disease appeared to be free of disease five years after the transplant and this finding raised hope that breast cancer could eventually take its place among the malignancies that are curable by chemotherapy. In 1993, a highly provocative study was published by Peters and colleagues, which showed that high-dose chemotherapy administered in the adjuvant setting to patients with high-risk primary breast cancer could achieve a 5-year disease-free survival of 70%. This appeared to be dramatically superior to conventional chemotherapy in historical controls [2]. Supported by a strong rationale derived from laboratory studies [3], but in the absence of data from randomised trials, high-dose chemotherapy was adopted as a potentially curative treatment option. Particularly in the United States, randomised studies with a conventional control arm were difficult to conduct since patients and doctors alike believed in the concept. As a result, the number