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Five
years of glioblastoma multiforme (GBM) phase II trials at the radiation therapy
oncology group (RTOG)
Wendy F
Seiferheld, Minesh P Mehta, John Del Rowe, David MacDonald, Corey Langer,
Charles Scott, Walter J Curran, W. K. Alfred Yung
American College of
Radiology, Philadelphia, PA; University of Wisconsin, Madison, WI; Montefiore
Medical Center, Bronx, NY; University of Western Ontario, London, ON, Canada;
Fox Chase Cancer Center, Philadelphia, PA; Thomas Jefferson University,
Philadelphia, PA; UT MD Anderson Cancer Center, Houston, TX
From 1995
to 2000, the RTOG completed five phase II trials of pharmacological agents
combined with standard radiation therapy (RT) for GBM.
The RTOG's development of
recursive partitioning analysis (RPA) classification for GBM patients enabled a
meaningful comparison of single arm trials against the RTOG GBM database of
patients treated with BCNU/RT regimens.
This approach facilitated the
exploration of several agents via phase II trials, rather than focusing
resources on a single-agent phase III trial.
During this period, the RTOG
enrolled 410 eligible patients onto five trials, replacing BCNU with either
tirapzamine, topotecan, taxol, beta interferon, or thalidomide.
Planned sample
size ranged from 53 to 84 patients, as the statistical design was modified over
time.
None of the experimental agents from these studies demonstrated
statistically significant improvement in survival from the historical control
after adjusting for RPA class.
On the other hand, it is important to realize
that several of the studies exhibited survival similar to the historical
control, and with fewer life-threatening toxicities. These results question the
standard practice of concurrent BCNU for GBM patients.
Furthermore, with the
observed low toxicity levels, phase II testing of doublet or triplet
combinations of these and other agents with RT is feasible, and may yield better
results than single-agent /RT approaches.
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Median
Survival (mo.)
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Overall
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RPA
III-IV
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RPA
V-VI
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Study
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N
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>=G4
Tox.
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Obs.
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Exp.
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Obs.
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Exp.
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Obs.
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Exp.
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9417:Tirapazamine
Arm 1: 159 mg/m2
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53
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2%
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10.8
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10.8
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12.8
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12.9
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7.9
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8.0
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9417:Tirapazamine
Arm 2: 260 mg/m2
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68
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11%
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9.5
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9.7
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11.5
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12.0
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5.0
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8.1
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9513:
Topotecan
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79
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54%
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9.3
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10.1
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10.3
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12.0
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5.5
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8.2
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9602:
Paclitaxel
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61
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13%
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9.7
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9.6
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11.1
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12.6
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6.4
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7.7
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9710:
β-Interferon
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60
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2%
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13.2
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10.3
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14.1
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12.6
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10.7
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8.2
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9806:
Thalidomide
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89
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8%
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10.0
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9.5
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14.4
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12.4
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4.3
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7.9
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Obs.=
Observed, Exp.= Expected (from historical control)
©
Copyright 2002 American Society of Clinical Oncology
Source:
http://www.asco.org/ac/1,1003,_12-002324-00_18-002002-00_19-00281-00_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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