Laboratory and experimental data show a dose response curve
for cytostatic drugs, especially for alkylating agents. For many
malignancies, clinical evidence of a dose response relationship
is limited.
The dose limiting toxicity of most cytostatic drugs is myelosuppression,
which can be circumvented by the use of haematopoietic
growth factors and/or autologous hone marrow or
peripheral stem cell support. Clinical data derived from studies in patients with metastatic
breast cancer, show that dose escalations of 1.5-2 x standard
dosages, possible without autologous bone marrow or peripheral
stem cell transport can induce higher remission rates,
which did not, however, correspond to a significant survival
advantage. Despite promising results from small trials with
high dose intensity treatment in combination with peripheral
stem cell or bone marrow support (depending on the schedule
used, dose escalations possible of 5-10 x the standard dosages)
in a selected patient population with high risk or metastatic
breast cancer, they do not justify the use of this approach outside
the setting of clinical studies. We have to gain more
knowledge of selecting the patients who are likely to profit
from high dose chemotherapy as well as to continue focusing
on improvement of efficacy, reduction of the considerable
morbidity and costs of this treatment
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