Comparison of the clinical efficacy of temozolomide (TMZ) versus nimustine (ACNU)-based chemotherapy in newly diagnosed glioblastoma.

Abstract

Although temozolomide (TMZ) replaced nitrosoureas as the standard initial chemotherapy for glioblastoma (GBM), no studies have compared TMZ with nimustine (ACNU), a nitrosourea agent widely used in central Europe and most Asian regions. One hundred thirty-five patients with GBM who underwent extensive tumor resection in our institution received both radiation and chemotherapy as initial treatment, 34 received TMZ and 101 ACNU-based (ACNU plus teniposide or cisplatin) chemotherapy. Efficacy analysis included overall survival (OS) and progression-free survival (PFS). The following prognostic factors were taken into account: age, performance status, extent of resection, and O(6)-methylguanine-DNA-methyltransferase (MGMT) gene status. The median OS was superior in the TMZ versus the ACNU group (p = 0.011), although MGMT gene silencing, which is associated with a striking survival benefit from alkylating agents, was more frequent in the ACNU group. In multivariate Cox analysis adjusting for the common prognostic factors, TMZ chemotherapy independently predicted a favorable outcome (p = 0.002 for OS, hazard ratio [HR], 0.45; p = 0.011 for PFS, HR, 0.56). Given that >40 % of patients in ACNU group did not receive the intensive chemotherapy cycles because of severe hematological and nonhematological toxicity, we performed a further subanalysis for patients who received at least 4 cycles of chemotherapy. Although a modest improvement in survival occurred in this ACNU subgroup, the efficacy was still inferior to that in the TMZ cohort. Our data suggest that the survival benefit of TMZ therapy is superior to that of an ACNU-based regimen in patients with extensive tumor resection, also shows greater tolerability.

• Authors: Yongzhi Wang, Xuzhu Chen, Zhong Zhang, Shouwei Li, Baoshi Chen, Chenxing Wu, Lei Wang, Xinzhong Zhang, Jiayin Wang, Ling Chen, Tao Jiang
• Journal: Neurosurgical review (Neurosurg Rev) Vol. 37 Issue 1 Pg. 73-8 (Jan 2014) ISSN: 1437-2320 [Electronic] Germany
• PMID: 23912878 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Antineoplastic Agents, Alkylating
• Tumor Suppressor Proteins
• Nimustine
• Dacarbazine
• DNA Modification Methylases
• MGMT protein, human
• DNA Repair Enzymes
• Temozolomide

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Agents (adverse effects, therapeutic use)
• Antineoplastic Agents, Alkylating (adverse effects, therapeutic use)
• Brain Neoplasms (drug therapy, pathology, therapy)
• Chemoradiotherapy, Adjuvant
• Combined Modality Therapy
• DNA Modification Methylases (genetics)
• DNA Repair Enzymes (genetics)
• Dacarbazine (analogs & derivatives, therapeutic use)
• Female
• Glioblastoma (drug therapy, pathology, therapy)
• Humans
• Kaplan-Meier Estimate
• Karnofsky Performance Status
• Male
• Middle Aged
• Nimustine (adverse effects, therapeutic use)
• Survival Analysis
• Temozolomide
• Tumor Suppressor Proteins (genetics)
• Young Adult