Dose-intensified treatment of breast cancer: current results

Chemotherapy has an established role in the treatment of carcinoma of the mammary gland (breast cancer), but when administered at conventional doses the net benefit in terms of relapse prevention and overall survival duration remains limited largely to operable patients at first diagnosis with limited tumor burden (stage II disease with less than four involved axillary lymph nodes). Pilot studies evaluating significant dose escalation in patients with advanced disease have yielded high remission rates, but the impact on long-term survival remains controversial. Recent trials involving dose-intense treatment in stage IV breast cancer do not support its use except in patients who have achieved complete remission or show no evidence of disease prior to high-dose consolidation. More optimism may be warranted for the use of dose-intense chemotherapy in the high-risk adjuvant setting (stage II/IIIA) and as part of the initial treatment for patients with inflammatory breast cancer or locally advanced primary inoperable carcinoma (stage IIIB). Prospective randomized trials in all settings are ongoing, although definitive results are not expected before 1998. Apart from single-course myeloablative high-dose chemotherapy, the availability of hematopoietic growth factors through recombinant DNA technology and the easy procurement of hematopoietic cell support through mobilization of peripheral blood progenitors has spurred the development of new strategies employing dose-intense treatment within the past 10 years. Repetitive application of chemotherapy at submyeloablative doses and sequential accelerated dose-intense application of single agents are now increasingly being integrated into more complex dose-escalated protocols. This review will focus on the results of mature trials and newer approaches to dose escalation.