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High dose chemotherapy: rationale and results in breast carcinoma
1Yorkshire Cancer Research, Department of Clinical Oncology, Cancer Research Centre, Weston Park Hospital, Sheffield, England.
Background:
High dose chemotherapy (HDC) with hematopoietic stem cell support is an increasingly important strategy in the management of advanced cancer. Early Phase II studies and the development of peripheral blood stem cell support to enable safe and tolerable myeloablative chemotherapy has resulted in its controversial and widespread use in the management of breast carcinoma. Recently, several randomized trials of both advanced breast carcinoma and the adjuvant setting have been reported.
Methods:
The technical developments in HDC and results from the randomized clinical trials reported to date were reviewed.
Results:
Three randomized trials of advanced breast carcinoma and five of high risk adjuvant patients were identified. Only two relatively small trials from South Africa have so far shown an advantage for high dose chemotherapy, and the validity of these trials has recently been seriously challenged. A Scandinavian adjuvant trial showed no advantage for HDC when compared with maximum nonablative doses supported with granulocyte-colony stimulating factor (G-CSF). Four trials were too small to detect clinically realistic differences in outcome, whereas the other large adjuvant trial was reported prematurely and the results in the HDC arm were dominated by high procedure-related mortality.
Conclusions:
It is difficult to make specific treatment recommendations based on the conclusions from the currently available data. The 1999 American Society of Clinical Oncology reports were inconsistent and in some cases were presented before the results were sufficiently mature to provide statistically reliable data. However, it is clear that, unlike in leukemia, lymphoma, and multiple myeloma, HDC in breast carcinoma should not be used outside the context of a clinical trial. The mature results of the ongoing trials are eagerly awaited, whereas the use of immediate as opposed to consolidation high dose treatment, tandem transplants, and developments in immunologic and genetic manipulation of the graft merit further evaluation.