A critique of the eleven randomised trials of high-dose chemotherapy for breast cancer.

Data from 11 randomised studies on high-dose chemotherapy for breast cancer are currently available. Most investigators, patients and insurers would agree that the two discredited South African trials are uninterpretable, and that the Scandinavian trial (which compares one very high-dose cycle versus six escalated dose cycles) does not ask the question of high-dose therapy versus conventional-dose therapy. Only two of the eight remaining studies randomised more than 200 patients (783 patients for the Cancer and Leukaemia Group B (CALGB) and 885 for the Dutch study). Both of these studies have trends in relapse-free survival favouring high-dose therapy. In a planned analysis of the first 284 patients entered into the Dutch study, with a median follow-up approximately 7 years, both disease-free and overall survival were significantly improved in the high-dose therapy arm. These and the other trials are discussed in detail below.