Temozolomide during and after radiation therapy for WHO grade III gliomas: preliminary report of a prospective multicenter study

Abstract

This prospective study was performed to determine the efficacy, safety, and tolerability of concurrent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy with temozolomide (TMZ) in the treatment of patients with WHO grade III gliomas. Thirty-three adult patients with WHO grade III glioma and aged >17 years were enrolled from three institutions between 2003 and 2008. The median age was 41 years (range, 17-60 years). The pathological diagnoses were anaplastic astrocytomas in 21 patients and anaplastic oligodendrogliomas in 12 patients. The preoperative Karnofsky performance scale score was >60 for all patients. The patients received fractionated focal irradiation in daily fractions of 2 Gy administered five days per week for six weeks, for a total of 60 Gy, in combination with continuous daily TMZ, followed by six cycles of adjuvant TMZ. The median dose of radiotherapy was 59.4 Gy (range, 28.8-61.2 Gy) and the duration of CCRT was 7.0 weeks (range, 3.1-8.3 weeks). A median of 6.2 cycles (range, 2-12 cycles) of TMZ chemotherapy were performed during the period of adjuvant chemotherapy. The response rate was 61% and the tumor-control rate was 82%. Mean progression-free survival (PFS) was 48.7 months (95% CI, 36.0-61.4) and the 12, 24, and 36-month PFS was 74%, 60%, and 50%, respectively. Mean overall survival (OS) was 66.4 months (95% CI, 56.4-76.4) and the 12 and 24-month OS was 97% and 77%, respectively. The extent of surgical resection was a significant prognostic factor for PFS and OS (hazard ratio, 0.24; 95% CI, 0.02-0.73; and hazard ratio, 0.12; 95% CI, 0.01-0.88, respectively; P < 0.001). However, there was no significant difference in the PFS and OS of patients regarding loss of heterozygosity in chromosomes 1p and 19q and methylation of O (6)-methylguanine-DNA methyltransferase promoter, because of the small number of patients available. Only five cases (15%) receiving CCRT with TMZ and three cases (9%) receiving adjuvant chemotherapy had hematological toxicity greater than grade 3. All these patients, however, tolerated the therapy well enough to continue treatment. No opportunistic infections were noted. This protocol for WHO grade III gliomas was relatively safe and tolerable. It showed the possibility of achieving favorable results compared with those of historical controls. A randomized controlled study with a long-term follow-up may be mandatory to evaluate its efficacy.

Temozolomide during and after Radiotherapy for Newly Diagnosed Glioblastomas : A Prospective Multicenter Study of Korean Patients

“…In effect, the only significant prognostic factor of OS and PFS was the extent of surgical resection in this study. Recent studies also reported that the extent of surgical resection was a significant prognostic factor for patients with a primary glioblastoma3,8,11,16). These data suggest that the more favorable survival rate in our study as compared with Stupp's study may be due to the higher GTR rate.…”

“…Temozolomide, which is a second-generation oral alkylating agent, performs antitumor activity by methylating the guanine residues of tumor cell DNA, thus creating a mismatch that an enzyme repair system cannot fix2,8,15). Temozolomide has demonstrated antitumor activity in the treatment of malignant gliomas and has been approved for the treatment of recurrent malignant glioma and newly diagnosed glioblastoma1,5,6,17,20).…”

“…Since the Stupp report, most Korean institutions use this concurrent protocol with temozolomide for primary glioblastoma treatments. Some single center studies reported the outcome of CCRT followed by adjuvant chemotherapy with temozolomide for Korean patients using Stupp's regimen3,7,8,10,14).…”

Anaplastic glioma: current treatment and management

“…The role of RT plus concomitant and adjuvant TMZ in newly diagnosed AG has been evaluated only in four small retrospective studies, two with TMZ administered pre-RT followed by concomitant RT + TMZ [91,95] and two with concomitant RT + TMZ followed by up to 12 cycles of post-RT TMZ [96,97]. Two other series have reported on various combinations of RT and CT in AG (TABLE 5) [89,98].…”

High-grade glial tumors, survival & prognostic factors; 5-year experience from Ankara Oncology Hospital

“…Günümüzde ortanca genel sağkalım DSÖ grad 3 hastalarda üç yıl, grad 4 hastalarda 16-18 aydır ve bu oranlar 20 yıl öncesinden çok farklı değildir. [4,5] Bu çalışmada amaç, Ankara Onkoloji Eği-tim ve Araştırma Hastanesi Radyasyon Onkoloji Kliniği'nde radyoterapi uygulanan YGG tümörlü hastaların genel özelliklerini ve sağkalım süreleri-ni ve buna etki eden faktörleri geriye dönük olarak incelemek, sonuçları literatürle kıyaslamaktır. …”