Autologous Bone Marrow Transplantation - Blog Science Connections

Panel Discussion: Session VI 539
relapses in bulk sites and other sites, generally solitary. I don't feel we
reinfused a tumor, at least we don't have evidence of that.
DR. E. FREI: Roger (Dr. R. Herzig), this is a question for you. When one
uses agents in combination, there are obviously many variables to deal with.
Very often, for cells in culture the cells have to see both drugs together, and
not necessarily in sequence. And I noted that when you put BCNCI and
phenylalanine mustard together you gave the first for 3 days and the second
for the next 3 days. So, in fact, neither the host, probably, and certainly not the
tumor, saw the two drugs at the same time. I don't have a good answer for this
myself. I realize there are a lot of practicalities in those strategies. But I
wonder if when you do that you have truly tested the potential for synergism
between the two. Why did you do that, for example, rather than put them
together concurrently?
DR. R. HERZIG: Well, partly because we were embarking on our first trial
in putting them together and were worried about synergistic toxicity as well as
potential synergistic antitumor effect, particularly with liver. So we spaced
them out, giving them sequentially one after the other, or changing the order.
DR. DICKE: Dr. Miser, on what kind of data do you base that etoposide is
an effective drug?
DR. MISER: If you look at etoposide in spindle cell sarcomas, the
response rate is very low. If you look at etoposide as a single agent in small
round cell sarcomas, the response rate across the board is about 20-30%. If
you look at it in combination with ifosfamide, the response rate and also the
relapse rate in Ewing's sarcoma approach 100%. If you look at it in
combination with ifosfamide in rhabdomyosarcoma, it approaches 80%, and
it's on the basis of standard doses, 500 mg/m 2 of etoposide per course and 9
g/m 2
of ifosfamide per course. I think there may be some advantage to using
those two high-dose drugs together.
DR. DICKE: I think that there might be a dose response for etoposide, at
least in Ewing's sarcoma.
DR. R. HERZIG: I think that's as much my opinion as it is based on
documented fact and literature, but I would hold to that opinion, yes.
DR. DICKE: But, besides the combination of chemotherapy, which has
been designed by Norman Jaffe, who else has demonstrated a dose
response, and why are the responses still so poor with high-dose chemotherapy?
DR. R. HERZIG: The standard response rate of the intergroup rhabdomyosarcoma
trial and the intergroup Ewing's sarcoma trial with patients with
metastatic disease is approximately 50-60%. If you look at the Boston
Ewing's trial in which they used high-dose vincristine, Adriamycin, and
Cytoxan like mine, and if you look at my trial, our response rate in Ewing's