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

SUMMARY: AUTOLOGOUS MARROW TRANSPLANTATION
FOR SOLID TUMORS
Roger H. Herzig, M.D.
PHASE I STUDIES
Nearly twenty years ago, the Phase I single agent dose escalation studies
began. Alkylating agents were chosen because of their properties of little nonmyeloid
toxicity, a log-linear dose response relationship could be demonstrated
in vitro cell lines and in conventional dose clinical studies, and they are generally
non-cross resistant. These sequential, single agent studies defined the toxicity
and feasibility of dose-intensive therapy with marrow support. While novel
and unusual non-myeloid toxicity was discovered, more importantly, a further
dose-response for most agents was demonstrated. The Phase I studies left questions
of scheduling open, but it did lead to other trials using multiple agents
and/or multiple courses. What still remains is how to increase the therapeutic
index of increasing the efficacy while decreasing the toxicity of these dose-intensive
regimens.
PHASE II STUDIES
The Phase II studies of dose-intensive therapy demonstrated efficacy in a
number of tumors. These studies were generally conducted in patients with advanced,
refractory disease. Overall, a high response rate was seen, usually in excess
of 60% to 70%, of which 20-40% of the responses were complete. Of note,
about 10-15% of the patients achieved significant disease-free survival of more
than a year. The promising results in these trials led to the use of dose-intensive
therapy earlier in the course of the disease. The solid tumors that fall into this
category, in which the dose-intensive therapy is probably effective, include
breast, ovary, melanoma, testicular cancer, Ewing's sarcoma, and neuroblastoma.
A second group of tumor types in which the dose-intensive therapy is
possibly effective include colon, lung, glioblastoma, and metastatic carcinoma
adenocarcinoma of unknown primary. The results in these patients showed high
response rates but fewer patients with complete responses or with long-term,
disease-free survival. It would also probably be beneficial to use a dose-intensive
approach in these patients earlier in their treatment. There are some tumor types
in which the Phase II trials provided either insufficient data or the tumors were
unresponsive to high-dose therapy. Few patients with Wilm's tumor have been
treated, however, dramatic responses in some of these patients have been documented.
There has been a renewed interest in the non-Ewing's sarcomas, especially
in the European community, and again responses are seen even after conventional
therapy has failed. In the category of tumors that are unresponsive
include patients with renal cell carcinoma. None of the patients in several series
with this diagnosis responded to high-dose therapy.
SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION 251