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N997D: Pilot trial of CPT11 during RT
followed by CPT11 and BCNU in newly diagnosed glioblastoma (GBM)
patients: A North Central Cancer Group (NCCTG) study
K. A. Jaeckle, K.
V. Ballman, P. Schomberg, J. Uhm, B.
Schiethauer, C. Giannini, S. Felton, P.
Brown, B. C. Jan NCCTG
Mayo Clinic, Jacksonville, FL; Mayo
Clinic, Rochester, MN
Background. Prior studies
in gliomas have shown additive therapeutic effects of CPT11
and BCNU, and radiosensitizing effect of CPT11.
We evaluated the toxicity of RT and concurrent CPT11, followed
post-RT by BCNU plus CPT11 in patients (pts) with newly
diagnosed GBM.
Methods. All pts had GBM
(WHO Grade 4) by central review.
Those not receiving anticonvulsants (non-EIAC, Arm A) received
RT with concomitant CPT11 (125mg/M2/wk X 4, cycle 1), followed
post-RT by BCNU (100mg/M2 q 6 wk) + CPT11 (125 mg/M2/wk X 4,
q 6 wks, cycles 2–5).
Pts on EIAC (Arm B) received CPT11 (400mg/M2/wk X 4, cycle
1) during RT, then post-RT BCNU (100mg/M2 q 6 wk) + CPT11
(400mg/M2/wk q 6 wks, cycles 2–5).
Dose de-escalations (but no escalations) were
allowed.
Toxicity was graded by CTCAE v 3.0.
Results. All pts received
treatment, and ≥ 3 cycles were administered in 7/16
non-EIAC and 6/12 EIAC pts.
In Arm A (non-EIAC, 48 total cycles), the most frequent treatment-related
grade ≥ 3 toxicities included neutropenia (25%), leukopenia
(17%), and diarrhea (13%).
Although cycle 1 during RT in Arm A was tolerated,
unacceptable toxicity (hematologic) during cycles 2–5
required amending the protocol to reduce the CPT11 dose to
75 mg/M2/wk X 4 (cycles 2–5).
In Arm A, there were a total of 40 grade 3, five grade 4,
and one grade 5 (perforated ulcer) toxicities; 4 patients
went off study due to toxicity.
In Arm B (EIAC, 45 cycles), the most common treatment-related grade
≥ 3 toxicities included diarrhea (4%) and neutropenia (4%),
with nine total grade 3 events, but no grade 4 or 5 events.
Dose reductions were required in 10/12 EIAC pts, but no pt went
off study due to toxicity.
Three of 16 non-EIAC, and 4/12 EIAC pts completed study per
protocol.
Conclusions.
Protocol-specific acceptable toxicity parameters were met
for non-EIAC pts, using CPT11 (125mg/M2/wk X 4, cycle 1)
during RT, followed post-RT by BCNU (100mg/M2 q 6 wk) +
CPT11 (75 mg/M2/wk X 4, q 6 wks, cycles 2–5); and, for
EIAC pts, using CPT11 400 mg/M2/wk X 4 during RT, followed
post-RT by BCNU 100mg/M2 q 6 wk + CPT11 400 mg/M2/wk X 4
(cycles 2–5) q 6 wks.
An expanded NCCTG Phase II efficacy study is in progress,
utilizing these dose schedules.
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