TITLE:
Protracted Adjuvant Temozolomide in Glioblastoma Multiforme
AUTHORS:
Ahmed A. Refae, Ahmed Ezzat, Dina Ahmed Salem, Mervat Mahrous
KEYWORDS:
Glioblastoma Multiforme, Timozolomide, Protracted Course, Efficacy
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.6 No.8,
August
14,
2015
ABSTRACT: Purpose: Radiotherapy with concurrent
temozolomide (TMZ), followed by 6 cycles of adjuvant TMZ, is the standard of
care for newly diagnosed Glioblastoma Mulltiforme (GBM). However tumor
progression is the role with median survival of almost 14 months. With lack of
effective second line chemotherapy, many physicians and some guidelines
advocate prolonged use of adjuvant TMZ more than 6 months. We conduct this
study to test the efficacy of protracted adjuvant conventional dose TMZ over
the standard 6 doses of adjuvant TMZ. Material and Methods: This phase II trial
enrolled patients newly diagnosed as GBM, older than age 18 years, with a
Karnofsky performance score (KPS) of ≥60, Neurological Performance Scale (NPS)
of ≤3. Patients were randomly assigned to the standard concurrent
chemoradiotherapy (CCRT) followed by 6 cycles of adjuvant TMZ or the same
treatment with more than 6 cycles of adjuvant chemotherapy extended as long as
the patient in good performance, with no unacceptable toxicity, no signs of
disease progression. The primary end point was OS. Results: A total of 59
patients were recruited in the study and were randomized in two arms. 29
patients joined arm 1 aiming at receiving CCRT followed by adjuvant 6 cycles
TMZ (6 cycles arm) and 30 joined arm 2 aiming at receiving the same treatment
with more than 6 cycles of TMZ (>6 cycles). 16 patients managed to complete
the adjuvant 6 cycles in arm 1. 19 patients in arm 2, completed the 6 cycles
with additive more doses with a median of 11 cycles (range: 8 - 23 cycles).
Median PFS was 12.1 months for (6 cycles) arm, and 18.8 months for (>6
cycles) arm, HR 0.88 (95% CI: 1.185 - 4.901) (P 0.015); the overall survival
for (6 cycles) arm was 18.1 months, versus 24.1 months, HR 0.70 (95% CI: 1.007
- 4.037) (P 0.048). No significant added toxicity was notice and the 4 weekly
TMZ was well tolerated. Conclusion: This study concluded that protracted
adjuvant TMZ after concurrent chemoradiotherapy could be a feasible strategy
for GBM. This strategy warrants a large phase III randomized trial.