Autologous Bone Marrow Transplantation - Blog Science Connections

494 ABMT for Breast Cancer
approach in metastatic breast cancer have been limited, as reviewed recently
by Souhami and Peters (5). The largest trials have employed either single
agents not usually used as treatment for metastatic breast cancer (6-8) or
combinations of multiple alkylating agents (4). The latter approach seems to
be the most encouraging, resulting in a significant number of CRs. However,
the relative contributions of the individual agents have not been addressed.
The preliminary trial reported here demonstrates that high-dose cyclophosphamide
alone may produce responses in patients with breast cancer
refractory to standard doses of the same drug but is unlikely to result in a
significant number of CRs.
Since survival benefit often depends largely on attainment of CR, a
second drug was added to the treatment regimen in this trial. Even though
carmustine in phase 11 studies has only modest activity against breast
carcinoma, its addition to cyclophosphamide has resulted in CRs in two of
four patients treated thus far. Although more patients are needed for
confirmation, our results support the hypothesis that multiple high-dose
alkylating agents may be additive or even synergistic in the treatment of
metastatic malignancies.
The toxicity of this aggressive approach, though significant, was tolerable
in the patients with good pretransplant performance status. The treatment
cannot be recommended for those with significant functional impairment.
The shorter platelet recovery time of patients receiving cyclophosphamide
alone suggests that endogenous marrow recovery played a significant
role in hematopoietic reconstitution and supports the studies of Smith et al.
(9) indicating that autografting is unnecessary with this regimen. However,
the platelet recovery time of patients treated with cyclophosphamide plus
carmustine was identical to that of patients at our institution autografted after
marrow-lethal doses of cyclophosphamide and total body irradiation,
suggesting the need for stem cell rescue.
Although this preliminary study resulted in a high response rate, the
median duration of response was disappointingly short. The predominance
of local recurrences in relapsing patients indicates that the high-dose drug
regimens employed here failed to eradicate endogenous tumor. Since the
drug doses used are near the limit of their nonhematologic tolerance, it is
likely that either additional drugs or alteration of the timing of the procedure
will be necessary to achieve more meaningful disease control.
REFERENCES
1. Henderson IC. In Breast Cancer: Diagnosis and Management, BonadonnaG.ed. Wiley, New
York, 1984:247.
2. Frei E, Canellos GP. Am J Med 1980:69:585.
3. Peters WP. In Autologous Bone Marrow Transplantation: Proceedings of the First
International Symposium, Dicke KA, Spitzer G, Zander AR, eds. The University of Texas M. D.
Anderson Hospital and Tumor Institute at Houston, Houston, 1985:189.