autologous blood and marrow transplantation - Blog Science ...

Stiff, Kerger, and Bayer 385
patients in this group with a negative second look, the 5-year disease-free survival
(DFS) of 32.8% implies that the 12 patients with microscopic residual disease at
second look have a similar DFS after the single transplant procedure. For those
patients with bulky disease at the initiation of second-look surgery, the 5-year DFS
was 19.2%, and the 5-year survival was 33.8%.
These data appear superior for patients with a positive second look laparotomy
to that described for those treated with only conventional therapy after second-look
surgery. Considering recent reports of survival after second-look surgery for
optimal or suboptimal disease, and the fact that 42% of this group had suboptimal
disease at diagnosis, we would expect the median survival for this group to be ~45
months treated with conventional therapy rather than the 66 months reported.
Given the improvements in the conventional therapy for this tumor and the
patient selection biases inherent in these pilot studies of transplants as consolidation
therapy, the true value of transplantation in the initial management of
patients with advanced ovarian cancer will come only from randomized trials.
Certainly, the preliminary results of our ongoing paclitaxel, mitoxantrone, and
carboplatin trials would indicate that this therapy may be useful for this patient
group, and in the absence of a comparative trial, should be considered. However,
all eligible patients should be enrolled in any available comparative phase III trial.
Under the auspices of the National Cancer Institute (NCI), the GOG as well as
SWOG, CALGB, and ECOG recently began a randomized phase III trial. Patients
with stage III or IV disease who respond to four to six cycles of a platinum-based
regimen after debulking surgery and have a clinical CR (suboptimal III and IV) or
a PR documented by a second-look laparotomy will be randomized between six
cycles of paclitaxel (175 mg/m 3
over 3 hours) combined with carboplatin at an
AUC of 7.5 and a single transplant using the carboplatin, mitoxantrone, cyclophosphamide
regimen described by our program. The trial, which is expected to take 5
years, will include those initially debulked suboptimally including those with a
pathologic CR in view of their high expected relapse rate. Accrual has been slow
primarily because of the slow acceptance of this form of therapy by patients and
their physicians. Also, some transplant physicians feel that no conventional therapy
is acceptable for patients with a disease that has such a poor prognosis. Efforts to
improve the understanding of this therapy by patients and physicians and a clear
explanation of its rationale should help to increase accrual. Unlike the breast cancer
trials, the goal was to initiate this trial before the publication of extensive pilot data
indicating its effectiveness, which would result in patients demanding this therapy
at all costs. Fortunately, the insurance industry has in large measure supported this
trial, as it has the breast cancer transplant trials.
Alternative approaches such as that reported by Fennelly et al. 20
that explore
double-dose chemotherapy in rapid succession at the time of initial diagnosis with
stem cell rescue (dose-dense), followed by a single cycle of high-dose melphalan,