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

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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 O6-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.

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Acknowledgments

This study was supported by grants from National High Technology Research and Development Program (2012AA02A508; 2011AA020106), International Science and Technology Cooperation Program (2012DFA30470), National Natural Science Foundation of China (91229121), Beijing Municipal Education Commission Science and Technology Program (KM201010025015; KZ201310025024), and Key Project of Chinese Ministry of Education (210003).

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Correspondence to Tao Jiang.

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Silvia Hofer, Zürich, Switzerland

There is little knowledge on any superiority of one alkylating agent over another in the treatment of glioblastomas. A randomized controlled trial to answer this important question will not be feasible these days. In China, the nitrosourea nimustine is used quite often due to a limited access to the newer alkylating agent temozolomide (TMZ). The authors retrospectively compared the clinical efficacy of TMZ versus nimustine (ACNU)-based chemotherapy in newly diagnosed glioblastoma. Although the study design is retrospective and nonrandomized, the authors could demonstrate the efficacy of ACNU-based therapy to be inferior to that of TMZ in patient cohorts that were well matched related to prognostic factors. ACNU was more toxic, and thus, >40 % of patients in the ACNU group could not complete the planned 6 cycles of chemotherapy; they experienced dose reductions and treatment delays. There are some limitations to this study which are all discussed in the paper, e.g., ACNU-based chemotherapy did not get any concomitant treatment during radiation, which might have had a worse impact on outcome.

Renato V. La Rocca, Louisville, USA

Dr. Wang et al. provide a retrospective analysis of two different systemic treatment options in 135 patients with newly diagnosed glioblastoma patients at a premier institution in Beijing, China. The authors compare the clinical efficacy of nimustine (ACNU)-based chemotherapy with temozolomide and radiation as initial therapy in this patient population from March 2005 to March 2010. Given the constraints of a nonrandomized patient population and absence of concomitant radiation in one cohort, the results appear to favor the use of temozolomide and radiation with respect to outcome and toxicity. The impact of the significant toxicity of ACNU is particularly relevant in a patient population whose prognosis is measured only in months. The authors do, however, make reference to a cost-benefit analysis, noting a lack of cost-effectiveness of the temozolomide regimen in the context of resource-limited Chinese clinical practice and appealing for a reduction in its pricing. These data again confirm the Stupp regimen as the current global standard with respect to efficacy in patients with newly diagnosed glioblastoma.

Yongzhi Wang and Xuzhu Chen contributed equally to this work.

Tao Jiang and Ling Chen contributed equally as senior authors.

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Wang, Y., Chen, X., Zhang, Z. et al. Comparison of the clinical efficacy of temozolomide (TMZ) versus nimustine (ACNU)-based chemotherapy in newly diagnosed glioblastoma. Neurosurg Rev 37, 73–78 (2014). https://doi.org/10.1007/s10143-013-0490-x

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