Autologous Bone Marrow Transplantation - Blog Science Connections

524 Panel Discussion: Session V
to analyze. I think in a couple of them, the peak concentration was quite high. So
1 think that's a possibility, but fairly unlikely, 1 might add.
DR. WOLFF: 1 think that your data suggest that perhaps mucositis is a
multifactorial process. I also think that when we did our study years ago we
weren't quite aware of the prevalence of herpes simplex virus. 1 think that it is a
possibility that we underestimated what the MTD dose is, especially since
mucositis should probably never be an MTD unless it's a pan-mucositis, with the
whole gastrointestinal system involved.
Gary, I just want to tell you what we' re doing atVanderbilt. Since you showed
our slide I thought I would just tell you what our sequence is. We've developed a
systematic approach to adding drugs. Our first drug was etoposide and we
subsequently added cyclophosphamide and platinum. All the patients that you
showed were extensive-stage patients, so what we've seen is with the
combination of etoposide alone, etoposide plus Cytoxan, etoposide plus
Cytoxan plus platinum, is that our latest complete response rate, which were all
pathologically restaged, is now about 80% after two courses in extensive-stage
small cell cancer patients. Our study, which is going on right now, is a
randomization in limited-stage patients between two cycles of very high dose
intense therapy. 1 also have to state that we have never used a bone marrow
transplant in those patients so the doses that we' re giving right now are without
bone marrow transplant and those are 100/kg of Cytoxan, 1200/m 2
of
etoposide, and 120/m 2
of platinum for two cycles as initial therapy and as a
randomization for limited-stage patients between that therapy versus the same
therapy, only at lower doses. We think that we're seeing some long-term
disease-free survivors in extensive-stage patients and are quite anxious to move
that therapy into a population that's going to benefit more from it. A fourth
study that's currently going on in extensive-stage patients while they are in the
hospital is the combination of induction therapy with intense weekly myelosuppressive
therapy. We're keeping the patients in the hospital for about 8
weeks straight, and what we're seeing right now is extremely rapid, complete
responses 2 weeks after therapy.
DR. G. SPITZER: Steve, could I back you up a second? Tell us, in more
detail, what the therapy with the extensive-disease patients is.
DR. WOLFF: As mentioned earlier, there is an 80% complete pathological
response rate in extensive-stage patients. That therapy is now being tried
upfront in limited-stage patients who have been randomized with conventional
CEP. We're trying to show where there really is a meaningful dose-response
relationship in a tumor group, limited-stage, that may potentially benefit from
high-dose intensive therapy. And the next stage, which is the fourth, is to use
that induction therapy with extensive-stage patients but add weekly marrowtoxic
therapy for 8 weeks. 1 don't want to tell you of this study because it's just
been started but in the first couple of patients, we've seen, at this time, all