Perry James R, Rizek Philippe, Cashman Rosemary, Morrison Meredith, Morrison Tara
Crolla Family Brain Tumour Research Unit, Department of Medicine, Sunnybrook Health Sciences Center, University of Toronto, Toronto, Ontario, Canada.
Cancer. 2008 Oct 15;113(8):2152-7. doi: 10.1002/cncr.23813.
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.
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.
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.
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.
尽管一线治疗取得了进展，但关于多形性胶质母细胞瘤（GBM）复发时的治疗数据很少。替莫唑胺（TMZ）耐受性良好，如果采用新的给药方案，即使之前使用过TMZ，仍可能具有活性。
作者回顾了他们使用连续TMZ方案（每日50mg/m²）的经验，该方案在传统5天TMZ治疗进展后给予。患者分为3组：1）传统TMZ治疗进展后的GBM；2）标准同步和辅助TMZ治疗完成后首次复发的GBM；3）传统TMZ治疗第二次复发的其他间变性胶质瘤患者。
在第1组中，21例中位年龄为54岁（范围33岁至68岁）的患者接受了中位3个周期（范围2至12个周期）的连续TMZ治疗，剂量为50mg/m²。总体临床获益（完全缓解、部分缓解和疾病稳定）率为47%，6个月无进展生存期（PFS）为17%。在第2组中，14例GBM患者，中位年龄52岁（范围38岁至62岁），在初始TMZ/放疗（RT）和辅助TMZ治疗进展后接受连续TMZ治疗。辅助TMZ后的中位间隔时间为3个月（范围2个月至10个月）。给予TMZ的中位周期数为5个，6个月PFS为57%。在第3组中，14例中位年龄为49岁（范围34岁至56岁）的患者接受了连续TMZ治疗；观察到2例部分缓解和6例疾病稳定，6个月PFS为42%。毒性轻微且耐受性良好；淋巴细胞减少常见，但未发现严重的机会性感染。
尽管是回顾性研究，但我们的结果表明，尽管之前接受过TMZ治疗，连续每日给予TMZ仍是一种有效的治疗方案。该方案出色的耐受性可能使未来与其他烷化剂或新疗法联合使用成为可能。
