Temozolomide rechallenge in recurrent malignant glioma by using a continuous temozolomide schedule: the "rescue" approach.
BACKGROUND
Despite advances in first-line therapy, there are few data on treatment of glioblastoma multiforme (GBM) at recurrence. Temozolomide (TMZ) is well tolerated and may have activity despite prior TMZ exposure if novel dose schedules are used.


METHODS
The authors reviewed their experience with a continuous TMZ schedule (50 mg/m(2) daily), given at progression after conventional 5-day TMZ. Patients were reported in 3 groups: 1) GBM after progression on conventional TMZ; 2) GBM at first recurrence after completion of standard concomitant and adjuvant TMZ; and 3) patients with other anaplastic gliomas at second relapse on conventional TMZ.


RESULTS
In Group 1, 21 patients with a median age of 54 years (range, 33 years-68 years) received a median of 3 cycles (range, 2-12 cycles) of continuous TMZ at 50 mg/m(2). Overall clinical benefit (complete response, partial response, and stable disease) was 47%, with 6-month progression-free survival (PFS) of 17%. In Group 2, 14 patients with GBM, median age 52 years (range, 38 years-62 years) received continuous TMZ at progression after initial TMZ/radiotherapy (RT) and adjuvant TMZ. The median interval after adjuvant TMZ was 3 months (range, 2 months-10 months). A median of 5 cycles of TMZ was given, and 6-month PFS was 57%. In Group 3, 14 patients with a median age of 49 years (range, 34 years-56 years) received continuous TMZ; 2 partial responses and 6 with stable disease were seen, with a 6-month PFS of 42%. Toxicities were mild and well tolerated; lymphopenia was common but no serious opportunistic infections were identified.


CONCLUSIONS
Although retrospective, our results demonstrate that continuous daily administration of TMZ is an active regimen despite prior TMZ therapy. The excellent tolerability of this regimen may allow future combination with other alkylating agents or with novel therapies.
Perry
James R
JR
Crolla Family Brain Tumour Research Unit, Department of Medicine, Sunnybrook Health Sciences Center, University of Toronto, Toronto, Ontario, Canada. james.perry@sunnybrook.ca
Rizek
Philippe
P
Cashman
Rosemary
R
Morrison
Meredith
M
Morrison
Tara
T