|
|
Phase I trial of erlotinib with
radiation therapy (RT) in patients with glioblastoma multiforme (GBM)
S. Krishnan, P.
Brown, K. Ballman, J. Fiveash, J.
Uhm, C. Giannini, F. Geoffroy, L.
Nabors and J. Buckner
North Central Cancer Treatment
Group, Rochester, MN
Background. EGFR
inhibitors may potentiate the therapeutic efficacy of RT in
GBM patients.
To evaluate the toxicity and maximum tolerated dose (MTD)
of erlotinib plus RT in patients with GBM, we performed the
following phase I trial.
Methods. Patients were
stratified based upon the use of enzyme-inducing anticonvulsants (EIACs).
Patients with resected or biopsied GBM were treated with
erlotinib for a week prior to concurrent erlotinib and 6
weeks (60 Gy) of RT and maintained on erlotinib until progression.
The erlotinib dose was escalated in cohorts of 3 with a starting dose
of 100mg/day.
Intrapatient dose escalation was not allowed.
Response was evaluated by MRI and clinical assessment of neurological
status every two months.
Results. 20 patients were
enrolled; 19 are evaluable.
There were 14 males/5 females, median age 54 years; 7 had
undergone biopsy only/ 5 subtotal resections/ 7 gross total
resections.
Current dose level is 150mg/day erlotinib for patients not
on EIACs (group 1) and 200mg/day for patients on EIACs
(group 2).
MTD has not been reached.
DLTs associated with treatment have occurred in Group 1 at
100mg (1 pt with stomatitis, n=7) and at 150mg (no DLTs,
n=4).
No DLTs have occurred in Group 2 at 100mg (n=3), 150mg
(n=3) and 200mg (n=3) but dose was reduced to 150mg in 2 of
3 patients due to a bothersome rash.
With a median follow-up of 189 days, there were 8 deaths and
13 progressions.
Median time to progression was 161 days (95%CI: 109 to 216)
and median survival was 386 days (95% CI: 278 to NR).
Best objective response was known and evaluable in 13
patients: 9 had stable disease, 1 had no evidence of disease and
3 had early progression.
Conclusions. Toxicity is
acceptable at the current doses of erlotinib plus RT.
Accrual continues on both arms with the addition of
concurrent and adjuvant temozolomide in conjunction with
erlotinib and RT.
|
