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Survival
of adults with newly diagnosed glioblastoma multiforme (GBM) treated with
experimental agents and delayed radiation therapy (RT) versus experimental
agents and immediate radiation: the experience of the NABTT CNS consortium
Stuart
A Grossman, K Carson, Steve Piantadosi, J Fisher
The NABTT
CNS Consortium, Baltimore, MD
As
identification of agents with activity in GBM is a high priority, the NABTT CNS
Consortium has been screening novel cytotoxic agents for activity in newly
diagnosed patients with GBM prior to RT and conventional chemotherapy.
If activity is not seen in these patients (using 15 to 50 patients per study),
it is statistically unlikely the drug under study will be effective in GBM.
Since 1994, 368 adults with newly diagnosed GBM entered NABTT clinical trials:
149 patients with measurable disease after surgery joined Class A studies (1 to
3 months of novel chemotherapy followed by RT; endpoint is response) while 219
joined Class B studies (non-cytotoxic agents coupled with RT; endpoint is
survival).
Patients on Class A studies are followed closely with MRIs every 4-6 weeks and
RT is initiated at 3 months or with evidence of tumor growth.
Taxol, 9-AC, CI-980, PZA, and oxaliplatin have been studied using the Class A
design while RSR-13, suramin, penicillamine, and CAI have been tested in Class B
protocols.
The median survival for patients on Class A protocols was 10.1 months (95%
CI=8.2-10.7 months) and for Class B protocols was 11.9 months (95% CI=10.2-12.8
months).
However, patients on Class A protocols were older than those on Class B studies
(58.3 vs 55.8 years; p<0.05) and the number who had biopsies rather than
debulking surgery was higher (30% vs 18%; p<0.01).
In addition, median tumor measurements for patients on Class A protocols (where
measurable disease is required) were double those of patients on Class B
studies.
Cox proportional hazards regression analysis adjusting for age, KPS, and extent
of surgery comparing Class A to Class B survival provided a hazard ratio of 1.22
(95% CI=0.96-1.56) and a p-value of 0.11. NABTT continues to closely monitor
survival on Class A studies to ensure that the strategy to identify active
cytotoxic agents using previously untreated patients is not associated with
excess risk.
Selection bias appears to account for some of the currently observed survival
differences between NABTTs Class A and B protocols.
© Copyright 2002
American
Society of Clinical Oncology
Source:
http://www.asco.org/ac/1,1003,_12-002324-00_18-002002-00_19-00282-00_29-00A-00_42-00ONeill-00_43-00-00_44-00-00_45-00
Author-00_46-00Title-00_47-00Title-00_48-00and-00_49-00and,00.asp?cat=CNS+Tumors&parent=CENTRAL+NERVOUS+SYSTEM+TUMORS
&returnpid=2323
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