Abstract
Temozolomide (TMZ) has received much attention, notably in the treatment of malignant glioma and malignant melanoma. The objective of this study was to compare the clinical efficacy and safety of TMZ alone and TMZ-based combination drug therapy in patients with melanoma. Using “temozolomide” as a keyword combined with “melanoma” and “randomized controlled trials” as Medical Subject Headings, the following electronic databases were searched: the Cochrane library, MEDLINE, EBSCO, EMBASE, Ovid, cNKI, and cBMDisc. The evaluating indicators were overall response rate (ORR), 1-year survival rate, and several of the most frequent adverse events. Five randomized controlled trials met our criteria and were included in the meta-analysis, with a total of 703 participants (309 patients received TMZ alone, and 394 patients received combined regimens). The meta-analysis showed that the ORR for TMZ-based drug therapy was higher than TMZ alone [relative risk (RR) = 1.44; 95 % confidence interval (CI), 1.06–1.95], but the 1-year survival rate was not significantly different between the two groups (RR = 1.13; 95 % CI, 0.92–1.40). These results suggested that the impact of these increased response rates was not translated into a survival benefit. Moreover, we found no difference in the incidence of adverse events analyzed. The currently available evidence showed that the TMZ-combination therapy may moderately improve the response rate, but there was no corresponding increased toxicity. Future large-scale, high-quality, placebo-controlled, double-blind trials are needed.
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References
Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007;57:43–66.
Jiang G, Wei ZP, Pei DS, Xin Y, Liu YQ, Zheng JN. A novel approach to overcome temozolomide resistance in glioma and melanoma: inactivation of MGMT by gene therapy. Biochem Biophys Res Commun. 2011;406:311–4.
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.
Avril MF, Aamdal S, Grob JJ, Hauschild A, Mohr P, Bonerandi JJ, et al. Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study. J Clin Oncol. 2004;22:1118–25.
Bedikian AY, Millward M, Pehamberger H, Conry R, Gore M, Trefzer U, et al. Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group. J Clin Oncol. 2006;24:4738–45.
Jiang G, Li LT, Xin Y, Zhang L, Liu YQ, Zheng JN. Strategy for reversing resistance to temozolomide in malignant melanoma. Curr Med Chem. 2012;19:3886–92.
Lui P, Cashin R, Machado M, Hemels M, Corey-Lisle PK, Einarson TR. Treatments for metastatic melanoma: synthesis of evidence from randomized trials. Cancer Treat Rev. 2007;33:665–80.
Huncharek M, Caubet JF, McGarry R. Single-agent DTIC versus combination chemotherapy with or without immunotherapy in metastatic melanoma: a meta-analysis of 3273 patients from 20 randomized trials. Melanoma Res. 2001;11:75–81.
Reviewer manger (Rev Man) [Computer program] version 5.0 Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2008.
Yin ZQ, Zhang WM, Song GX, Luo D. Meta-analysis on the comparison between two topical calcineurin inhibitors in atopic dermatitis. J Dermatol. 2012;39:520–6.
Ranson M, Hersey P, Thompson D, Beith J, McArthur GA, Haydon A, et al. Randomized trial of the combination of lomeguatrib and temozolomide compared with temozolomide alone in chemotherapy naive patients with metastatic cutaneous melanoma. J Clin Oncol. 2007;25:2540–5.
Kaufmann R, Spieth K, Leiter U, Mauch C, von den Driesch P, Vogt T, et al. Temozolomide in combination with interferon-alfa versus temozolomide alone in patients with advanced metastatic melanoma: a randomized, phase III, multicenter study from the Dermatologic Cooperative Oncology Group. J Clin Oncol. 2005;23:9001–7.
Bafaloukos D, Tsoutsos D, Kalofonos H, Chalkidou S, Panagiotou P, Linardou E, et al. Temozolomide and cisplatin versus temozolomide in patients with advanced melanoma: a randomized phase II study of the Hellenic Cooperative Oncology Group. Ann Oncol. 2005;16:950–7.
Danson S, Lorigan P, Arance A, Clamp A, Ranson M, Hodgetts J, et al. Randomized phase II study of temozolomide given every 8 hours or daily with either interferon alpha-2b or thalidomide in metastatic malignant melanoma. J Clin Oncol. 2003;21:2551–7.
Bafaloukos D, Tsoutsos D, Fountzilas G, Linardou H, Christodoulou C, Kalofonos HP, et al. The effect of temozolomide-based chemotherapy in patients with cerebral metastases from melanoma. Melanoma Res. 2004;14:289–94.
Eberle J, Fecker LF, Hossini AM, Kurbanov BM, Fechner H. Apoptosis pathways and oncolytic adenoviral vectors: promising targets and tools to overcome therapy resistance of malignant melanoma. Exp Dermatol. 2008;17:1–11.
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This project is supported by Grants from the National Natural Science Foundation of China (No. 81372916).
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Jiang, G., Li, RH., Sun, C. et al. Efficacy and safety between temozolomide alone and temozolomide-based double therapy for malignant melanoma: a meta-analysis. Tumor Biol. 35, 315–322 (2014). https://doi.org/10.1007/s13277-013-1042-2
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DOI: https://doi.org/10.1007/s13277-013-1042-2