Autologous Bone Marrow Transplantation - Blog Science Connections

466 Treatment Strategies in Breast Cancer
Simultaneously, syngeneic and allogeneic transplantation with intensive
chemoradiation therapy has been shown to be curative for patients with
selected leukemias and lymphomas. Again, fundamental to the success of
these approaches was the recognition that treatment of early disease was
often far more effective and less toxic than the same therapy used as a last
resort.
Interest has been renewed recently in the treatment of breast cancer and
other solid tumors using intensive chemotherapy, and particularly intensive
combination chemotherapy with autologous bone marrow support (ABMS).
Our group has focused on this disease, attempting to evaluate therapeutic
regimens systematically based on biochemical and biological properties and
modifications of these regimens targeted at breast cancer.
CONCEPTS
The dose-response curve for chemotherapeutic agents in the treatment
of breast cancer is steep. Bonadonna and Valagussa (2) demonstrated a
major impact of dose on the treatment of metastatic breast cancer, and they
extended these findings to the adjuvant treatment setting. When Hryniuk and
Bush (3) analyzed treatment results from a number of clinical trials
employing CMF and cyclophosphamide, Adriamycin (doxorubicin), and
fluorouracil (CAF), they demonstrated a major influence of dose intensity on
the therapeutic outcome. The use of intensive chemotherapy with ABMS
resulted in objective response rates in resistant disease in excess of what
would have been generally expected (4-6). These observations provide
encouragement for the use of high-dose regimens in treating patients for
breast cancer.
Combination chemotherapy was demonstrated to be more effective than
single agents in the treatment of breast cancer (7). This observation is
consistent with treatment results for other diseases and predicts that, at high
doses, the use of combinations of agents is more likely to provide a
therapeutic advantage than the use of single drugs. Table 1 lists the response
rates in advanced breast cancer for several drugs used as single agents in
conventional doses. Dose escalation with bone marrow support was
undertaken with several of these agents and the maximum tolerated dose
established. Unfortunately, little information exists on the objective response
rates obtained at high doses with these drugs in patients with breast cancer.
It is relevant to high-dose combination chemotherapy efforts that the
nonmyelosuppressive dose-limiting toxicities encountered at high doses
differ among selected agents (8). This finding offers the opportunity of
combining several agents with differing nonmyelosuppressive toxicity using
ABMS. When this method was tested in a phase 1 trial of combination