We would suggest on the basis of our analysis that drug resistance still appears to represent a plausible explanation for
drug treatment failure in adjuvant breast
chemotherapy. It may not be the only factor, but, if present, clearly has to be circumvented if treatment results are to be improved. Since it seems most unlikely that a new wonder
drug for
breast cancer will emerge in the next few years, then it is to our existing armamentarium of
antineoplastic agents that we will have to turn for improved therapeutic results. Fundamental questions will need to be asked about what indeed are the most appropriate agents to be used in
combination chemotherapy protocols for this disease and what are the optimal dose ratios. Our own institutional experience in a number of areas has suggested that many chemotherapeutic protocols that are widely used represent significant underdosing and that achieving optimal results requires pushing therapeutic agents closer to the reasonable limits of tolerance. Enhanced techniques for patient support during programs of more intensive
chemotherapy are now available, and it has also been our experience that patients tolerate briefer, intensive programs of
chemotherapy better than they do protracted, less intensive protocols. The role of new
drug combinations that incorporate synergistic or significant biochemical modulation effects (i.e., platinum-etoposide, 5-fluorouracil-leucovorin) need to be examined in the context of the management of
breast cancer. We appear to have reached something of a plateau with existing protocols and approaches, and it is time to move ahead.