VI Autologous Bone Marrow Transplantation.pdf - Blog Science ...

PHASE III STUDIES
There are a very limited number of Phase III prospectively randomized trials
using dose-intensive therapy with marrow rescue for solid tumors. Currently,
the ones with the highest profile are the high-risk stage II-III breast cancer
studies that are being carried out collaboratively in the national cooperative
groups. Two such trials are underway. There have been no interim analyses of
survival or recurrence performed for these trials. Patient accrual is slow, but continues
at a reasonable pace. The preliminary data on toxicity of the treatment
(from the CALGB trial) has been acceptable. There is also a Phase III study for
advanced breast cancer randomizing complete responders to conventional
therapy to early verses late transplant. No results are available. At this point,
Phase III trials need to be carefully designed with appropriate questions asked.
Not all questions will need a Phase III trial; in some instances, it would be more
appropriate to devote more time and attention to increasing the therapeutic index
rather than asking inappropriate questions in a Phase III trial.
THERAPEUTIC INDEX
In order to increase the therapeutic index, one must decrease the toxicity
and/or increase the efficacy of the treatment. Currently, efforts for decreasing
toxicity have been aimed at supportive care issues, mediators of toxicity, and
attenuation of dose. The proliferation of hematopoietic growth factors, both before
and after the dose-intensive therapy, has made a small but significant impact
on the infectious complications following the dose intensive therapy. Erythropoietin
can reduce red blood cell transfusion requirements. As more growth
factors develop, the beneficial effects on other lineages may be similarly shown.
Other investigations have sought to block the mediators of toxicity, for example,
by blocking tumor necrosis factor with pentoxifylline. Mixed results have been
achieved with this approach, but the concept of blocking the mediators of toxicity
is valid. Finally, efforts at optimizing the dosing schedule could decrease the
toxicity. Attenuation of dose frequently reduces response, however, combining
agents that are hopefully synergistic with sub-additive toxicity will result in
lower toxicity and increased efficacy. Other ways at increasing efficacy could
also include multiple courses of either single or multiple agents, better drugs,
and obviously treating patients earlier in the course of their disease. The doseintensive
approach should not be an alternative to Hospice. Patients that have a
better performance status with less tumor bulk are likely to do better with a
dose-intensive approach.
OTHER ISSUES
Ehxring the meeting, much had been discussed concerning the source of
stem cells: bone marrow, peripheral blood, or both. The question should not be
which is better, but rather how can we most effectively use this supportive care
measure to provide the best effect. In future meetings, we may even want to
change our title from autologous transplantation to something else because the
stem cell support is really a supportive care issue, not a therapeutic one.
As this treatment modality becomes used earlier, detection of minimal, residual
disease will play an increasing role. It will also be an important way for
negative selection of a stem cell product, i.e., to select cells that do not have tu-
252 SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION