Autologous Bone Marrow Transplantation - Blog Science Connections

Treatment Strategies in Breast Cancer 471
patients and survival for all treated patients. The median time to treatment
failure for patients who had received previous chemotherapy was shorter than
for patients who had received no chemotherapy (88 versus 225 days; P, .014).
Similarly, the median survival for all treated patients was longer for those who
had received no previous chemotherapy compared with previously treated
patients (390 versus 102 days; P, .004).
The toxicity associated with high-dose combination alkylating-agent
therapy is substantial. Among the 33 treated patients, seven therapy-related
deaths occurred—an overall treatment-related mortality rate of 2156. Toxicity
seems to be increased by a patient's reduced performance status before
therapy, extensive previous therapy, especially with doxorubicin and radiation,
and the presence of bulk disease at the start of therapy. Late opportunistic
infections occurred in seven patients, perhaps related to inversion of the
T-cell subsets that have persisted beyond 1 year from therapy (18)
(unpublished data).
DISCUSSION
Intensive chemotherapy with ABMS is capable of producing a high
objective response rate in patients with metastatic breast cancer. Although
the regimen may produce regression of disease in patients who have received
previous chemotherapy, the duration of their response is short and therapyrelated
complications are frequent. When used as initial treatment for
metastatic disease, frequent, rapid, and complete responses occur. Relapse
remains common, however, the median response duration being 7.5 months.
Relapse occurs most often (according to data not presented here) at
pretreatment sites of bulk disease, suggesting that additional surgery or
radiation therapy may prove of benefit. The difference in time to treatment
failure (Fig 1) between patients having received previous chemotherapy or
not for metastatic disease most likely represents differences in the intrinsic
resistance of extensively treated disease. The different treatment programs
(cyclophosphamide, cisplatin, and carmustine compared with cyclophosphamide,
cisplatin, and melphalan or thio-TEPA) may, however, be less
effective.
The major limitation of the therapeutic approach described here seems
to be the timing of treatment. Treatment of patients with resistant, relapsed
acute leukemia or lymphoma with intensive chemoradiation therapy and
marrow transplantation produced few long-term survivors and a high toxicity
rate. When this therapy was applied during remission, however, especially
first remission, more patients were cured and the toxicity became less
pronounced. The breast cancer patients described here represent patients in
first relapse and resistant relapse.
To be more effective, this therapy needs to be attempted at earlier or at
least during more favorable disease states. Table 4 lists the extent of breast