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

BONE MARROW TRANSPLANTATION FOR OVARIAN CARCINOMA IN
THE UNITED STATES: A SURVEY OF ACTIVE PROGRAMS
Patrick Stiff M.D. 1
, Karen Antman M.D. 2
, E. Randolph Broun M.D. 3
,
Robert Collins M.D. 4
, Karen Fields M.D. 5
, Anne Kessinger M.D. 6
,
Thomas Shea M.D. 7
, Elizabeth Shpall M. D. 8
, and Gary Spitzer M.D. 9
'Loyola University Medical Center, Maywood, IL; 2
Dana Färber Cancer Center,
Boston, MA; Tndiana University, Indianapolis, IN; 4
Baylor University Medical
Center, Dallas, TX; 5
H. Lee Moffitt Cancer Center, Tampa, FL; 'University of
Nebraska, Omaha, NE; university of North Carolina, Chapel Hill, NC;
8
University of Colorado, Denver, CO; 9
St. Louis University, St. Louis, MO
INTRODUCTION
Ovarian carcinoma is the the fourth most common cause of cancer death in
women in the United States. Almost 80% present with advanced disease and
despite initial responses to platinum-based chemotherapy, in approximately 70-
80%, only 20% are long term survivors 1
. Only 30% respond to conventional salvage
therapy, with response durations usually lasting only a few months. While
new agents such as taxol 2
might improve the prognosis of patients with advanced
ovarian carcinoma when used early, the incurability of relapsed and all
but minimal disease at the time of second look surgery have led many groups to
explore new approaches for these patients. These include dose-intensive therapy
given as either intraperitoneal chemotherapy and or systemic chemotherapy
with either myeloid growth factors or autologous bone marrow transplantation
(ABMT).
While intraperitoneal therapy appears promising for the 20% of patients
with < 0.5 cm of disease at the time of second look surgery, still 80% of this
highly select group of patients ultimately die of their disease 3
. However these
responses and the in vitro and in vivo evidence of a favorable dose-response
curve for many of the active agents used to treat patients with ovarian carcinoma
has led to investigation of dose-intensive systemic chemotherapy, with
growth factors or with autologous bone marrow transplantation (ABMT). Evidence
to support the concept of dose escalation in ovarian carcinoma exists for
platinum compounds, alkylating agents and mitoxantrone. Bruchner and Ozols
administered cisplatin at the upper limit of the conventional range of 200 mg/m 2
to patients not responsive to lower doses of this agent and observed a response
rate of 20-32% 43
. Cisplatin doses can not be escalated further however because
of neurotoxicity. The dose limiting toxicity for carboplatin on the other hand is
hematopoietic. Carboplatin doses up to 800 mg/m 2
have in fact been administered
with GM-CSF and without bone marrow rescue. Responses of 35% have
been seen which are approximately twice that for more conventional doses of
the drug 6
. However while the response rates are higher and infections are controlled
with GM-CSF, the patients are severely thrombocytopenic and thus full
treatment courses can not be routinely given at the full dose.
192 SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION