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A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse
Open accessAbstract
A randomized, multicentre, open-label, phase II study compared temozolomide (TMZ), an oral second-generation alkylating agent, and procarbazine (PCB) in 225 patients with glioblastoma multiforme at first relapse. Primary objectives were to determine progression-free survival (PFS) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment. Secondary objectives were to assess overall survival and health-related quality of life (HRQL). TMZ was given orally at 200 mg/m(2)/day or 150 mg/m(2)/day (prior chemotherapy) for 5 days, repeated every 28 days. PCB was given orally at 150 mg/m(2)/day or 125 mg/m(2)/day (prior chemotherapy) for 28 days, repeated every 56 days. HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 [+3]) and the Brain Cancer Module 20 (BCM20). The 6-month PFS rate for patients who received TMZ was 21%, which met the protocol objective. The 6-month PFS rate for those who received PCB was 8% (P = 0.008, for the comparison). Overall PFS significantly improved with TMZ, with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group (P = 0.0063). The 6-month overall survival rate for TMZ patients was 60% vs. 44% for PCB patients (P = 0.019). Freedom from disease progression was associated with maintenance of HRQL, regardless of treatment received. TMZ had an acceptable safety profile; most adverse events were mild or moderate in severity.
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“The average historical PFS6 based on the above studies is 15.3 ± 3.8%”
From Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors (2007) · cites this paper as [25]
In the citing paper
“and the average historical TTP is 9.5 ± 1.6 weeks.”
From Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors (2007) · cites this paper as [25]
In the citing paper
“OS averaged 29.3 ± 6 weeks (see SI Table 2).”
From Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors (2007) · cites this paper as [25]
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“Efficacy analysis was performed for 10 recurrent GBM patients by comparing TTP, PFS6, and OS in recurrent GBM patients treated with the NovoTTF-100A device with the TTP, PFS6, and OS of recurrent GBM patients in a literature based historical control group (10, 25–28).”
From Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors (2007) · cites this paper as [25]
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“A 10-unit change on a 0–100 scale was deemed significant if it lasted for at least 8 weeks (Jaeschke et al, 1989; Juniper et al, 1994; King, 1996; Ware et al, 1998).”
The interpretation of scores from the EORTC quality of life questionnaire QLQ-C30
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Phase I trial of temozolomide (CCRG 81045: M&B 39831: NSC 362856)
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“TMZ has notable antitumour activity against recurrent GBM, recurrent anaplastic astrocytoma, and advanced malignant melanoma, and other refractory cancers (Newlands et al, 1992, 1996; O’Reilly et al, 1993; Bleehen et al, 1995; Bower et al, 1997).”
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Radiotherapy Plus Concomitant and Adjuvant Temozolomide for Glioblastoma
Stupp, R., Mason, W. P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J. B., Belanger, K., Brandes, A. A., Marosi, C., Bogdahn, U., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa043330 · Cited by 21,807
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“Despite therapy, 6-month progression-free survival (PFS) for relapsed or progressive glioblastoma is 9% to 21%, objective response (OR) rate is less than 10%, and median overall survival (OS) is 30 weeks or less.(2-8) Thus, recurrent glioblastoma remains a largely unmet medical need, which highlights the need for nove…”
BackgroundSelf-citationMalignant astrocytic glioma: genetics, biology, and paths to treatment
Furnari, F. B., Fenton, T., Bachoo, R. M., Mukasa, A., Stommel, J. M., Stegh, A., Hahn, W. C., Ligon, K. L., Louis, D. N., Brennan, C., et al. (2007) · Genes & Development · doi:10.1101/gad.1596707 · Cited by 2,316
“In comparison, TMZ given at first recurrence in GBM yields a PFS6 of 21% (Yung et al. 2000).”
BackgroundBevacizumab Plus Irinotecan in Recurrent Glioblastoma Multiforme
Vredenburgh, J. J., Desjardins, A., Herndon, J. E., Marcello, J. E., Reardon, D. A., Quinn, J. A., Rich, J. N., Sathornsumetee, S., Gururangan, S., Sampson, J. H., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.12.2440 · Cited by 1,417
“This study was conducted to improve the prognosis for recurrent GBM, for which response to therapy has generally been less than 20% and 6-month PFS less than 30%.(19-22) Although temozolomide in combination with radiation therapy followed by 6 months of temozolomide has become the standard of care for newly diagnosed…”
MethodSelf-citationPhase II Trial of Bevacizumab and Irinotecan in Recurrent Malignant Glioma
Vredenburgh, J. J., Desjardins, A., Herndon, J. E., Dowell, J. M., Reardon, D. A., Quinn, J. A., Rich, J. N., Sathornsumetee, S., Gururangan, S., Wagner, M., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2309 · Cited by 1,094
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Self-citationAlternating electric fields arrest cell proliferation in animal tumor models and human brain tumors
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Standards of care for treatment of recurrent glioblastoma—are we there yet?
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“Statistical Considerations Because previous studies for patients with recurrent glioblastoma have shown a 6-month PFS rate of approximately 21% [25], this single-stage study of 53 assessable patients was designed to differentiate between a 6-month PFS rate of 15% and 30% with type I and II error rates of 0.”
BackgroundSelf-citationMetabolic Modulation of Glioblastoma with Dichloroacetate
Michelakis, E. D., Sutendra, G., Dromparis, P., Webster, L., Haromy, A., Niven, E. B., Maguire, C., Gammer, T.-L., Mackey, J. R., Fulton, D. S., et al. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3000677 · Cited by 744
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Central Nervous System Cancers, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology
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Self-citationTemozolomide as Monotherapy Is Effective in Treatment of Advanced Malignant Neuroendocrine Tumors
Ekeblad, S., Sundin, A., Janson, E. T., Welin, S., Granberg, D. O., Kindmark, H., Dunder, K., Kozlovacki, G., Örlefors, H., Sigurd, M., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2053 · Cited by 470
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Self-citationPhase I/II Trial of Intravenous NDV-HUJ Oncolytic Virus in Recurrent Glioblastoma Multiforme
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Recurrent glioma clinical trial, CheckMate-143: the game is not over yet
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Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse
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“We evaluated the therapeutic efficacy of single-agent temozolomide, an oral imidazotetrazine recently introduced for the management of malignant glioma at recurrence [19, 21, 22, 28, 29].”
BackgroundSelf-citationAgarwala, S. S., Kirkwood, J. M., Gore, M. E., Dréno, B., Thatcher, N. J., Czarnetski, B., Atkins, M. B., Buzaid, A. C., Skarlos, D. V., & Rankin, E. M. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.11.044 · Cited by 362
Immediate post-radiotherapy changes in malignant glioma can mimic tumor progression
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Reardon, D. A., Egorin, M. J., Quinn, J. A., Rich, J. N., Gururangan, I., Vredenburgh, J. J., Desjardins, A., Sathornsumetee, S., Provenzale, J. M., Herndon, J. E., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.03.2185 · Cited by 329
Self-citationHealth-related quality of life in patients with glioblastoma: a randomised controlled trial
TAPHOORN, M. J. B., Stupp, R., Coens, C., Osoba, D., Kortmann, R. D., van den Bent, M. J., Mason, W. P., Mirimanoff, R. O., Baumert, B. G., Eisenhauer, E. A., et al. (2005) · The Lancet Oncology · doi:10.1016/s1470-2045(05)70432-0 · Cited by 326
Self-citationChemoresistance of glioblastoma cancer stem cells - much more complex than expected
Beier, D., Schulz, J. B., & Beier, C. P. (2011) · Molecular Cancer · doi:10.1186/1476-4598-10-128 · Cited by 308
“While alkylating substances such as nimustine (ACNU), carmustine (BCNU), and lomustine (CCNU) have been used since the late 1970s [1,2], the introduction of temozolomide (TMZ) as standard treatment paved the way for a broader use of chemotherapy in the treatment of GBM [3,4].”
BackgroundHermisson, M., Klumpp, A., Wick, W., Wischhusen, J., Nagel, G., Roos, W. P., Kaina, B., & Weller, M. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03583.x · Cited by 318
Recent Advances in the Treatment of Malignant Astrocytoma
Reardon, D. A., Rich, J. N., Friedman, H. S., & Bigner, D. D. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.04.5302 · Cited by 309
Self-citationStummer, W., Tonn, J., Mehdorn, H. M., Nestler, U., Franz, K., Goetz, C., Bink, A., & Pichlmeier, U. (2010) · Journal of neurosurgery · doi:10.3171/2010.3.jns097 · Cited by 313
Nonsurgical Treatment of Recurrent Glioblastoma
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“have demonstrated reasonable efficacy and an acceptable toxicity profile with temozolomide in the setting of recurrent GB (Yung et al., 2000).”
Kunwar, S., Prados, M. D., Chang, S. M., Berger, M. S., Lang, F. F., Piepmeier, J. M., Sampson, J. H., Ram, Z., Gutin, P. H., Gibbons, R. D., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.08.1117 · Cited by 325
Self-citationQuinn, J. A., Desjardins, A., WEINGART, J. D., Brem, H., Dolan, M. E., Delaney, S. M., Vredenburgh, J. J., Rich, J. N., Friedman, A. H., Reardon, D. A., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.06.502 · Cited by 288
“Seven patients with stable disease continued on treatment, having received a median of fivecycles(range,threeto12).Onepatient( 8 )demonstrateda complete response (Fig 1) and remains free of disease after 12 cycles of temozolomide and 33 months off therapy.”
BackgroundSelf-citationRecurrent glioblastoma multiforme: a review of natural history and management options
Hou, L. C., Veeravagu, A., Hsu, A. R., & Tse, V. (2006) · Neurosurgical FOCUS · doi:10.3171/foc.2006.20.4.2 · Cited by 275
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RetractedAthanassiou, H., Synodinou, M., Maragoudakis, E., Paraskevaidis, M., Verigos, C., Misailidou, D., Antonadou, D., Saris, G., Beroukas, K., & Karageorgis, P. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.00.331 · Cited by 272
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“Improvements in radiographic and clinical response rates have been described in patients with HHGs treated with bevacizumab plus irinotecan when compared to historical data [9, 10].”
ResultMRI in patients with high-grade gliomas treated with bevacizumab and chemotherapy
Pope, W. B., Lai, A., Nghiemphu, P. L., Mischel, P. S., & Cloughesy, T. F. (2006) · Neurology · doi:10.1212/01.wnl.0000208958.29600.87 · Cited by 272
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“We performed a two-sided Fisher’s exact test to test for significance of the outcome in our study compared with the standard regimen.(8) Further patients with progressive gliomas have been included in the safety analysis, and efficacy data are reported.”
BackgroundMethodInfluentialUnderstanding high grade glioma: Molecular mechanism, therapy and comprehensive management
Wang, Y., & Jiang, T. (2013) · Cancer Letters · doi:10.1016/j.canlet.2012.12.024 · Cited by 264
Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas
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“The 35% response rate in WHO grade III astrocytoma (anaplastic astrocytoma) [5] in comparison with a 6–8% response rate in grade IV tumours (glioblastoma multiforme) [6, 7] suggests a possible trend of increasing efficacy in lower grade tumours previously noted for nitrosourea-containing chemotherapy [8].”
ResultSelf-citationCurrent Standards of Care in Glioblastoma Therapy
Fernandes, C. D., Costa, A., Osório, L., Lago, R. C., Linhares, P., Carvalho, B., & Caeiro, C. (2017) · Codon Publications eBooks · doi:10.15586/codon.glioblastoma.2017.ch11 · Cited by 275
“In both trials leading to the approval of TMZ, the sdTMZ schedule was used (126, 127).”
BackgroundMethodInfluentialPhase II Trial of Temozolomide in Patients With Progressive Low-Grade Glioma
Quinn, J. A., Reardon, D. A., Friedman, A. H., Rich, J. N., Sampson, J. H., Provenzale, J. M., McLendon, R. E., Gururangan, S., Bigner, D. D., Herndon, J. E., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.01.009 · Cited by 256
Self-citationTreg depletion with a low-dose metronomic temozolomide regimen in a rat glioma model
Banissi, C., Ghiringhelli, F., Chen, L., & Carpentier, A. F. (2009) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-009-0671-1 · Cited by 256
Current and future developments in the use of temozolomide for the treatment of brain tumours
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Temozolomide Versus Procarbazine, Lomustine, and Vincristine in Recurrent High-Grade Glioma
Brada, M., Stenning, S. P., Gabe, R., Thompson, L. C., Levy, D., Rampling, R., Erridge, S., Saran, F. H., Gattamaneni, R., Hopkins, K., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.1932 · Cited by 248
“006).(7) In a single-arm phase II study, the 6-month PFS in 138 patients with GBM was 18%.”
BackgroundResultSelf-citationNovel anti-angiogenic therapies for malignant gliomas
Norden, A. D., Drappatz, J., & Wen, P. Y. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70260-6 · Cited by 246
Antiangiogenic therapies for high-grade glioma
Norden, A. D., Drappatz, J., & Wen, P. Y. (2009) · Nature Reviews Neurology · doi:10.1038/nrneurol.2009.159 · Cited by 253
Current management of glioblastoma multiforme
Grossman, S. A., & Batara, J. F. (2004) · Seminars in Oncology · doi:10.1053/j.seminoncol.2004.07.005 · Cited by 243
Phase 1 trial of dichloroacetate (DCA) in adults with recurrent malignant brain tumors
Dunbar, E. M., Coats, B. S., Shroads, A. L., Langaee, T., Lew, A., Forder, J. R., Shuster, J. J., Wagner, D. A., & Stacpoole, P. W. (2014) · Investigational New Drugs · doi:10.1007/s10637-013-0047-4 · Cited by 241
“Recurrent malignant brain tumors (RMBTs), whether from primary malignant gliomas, or from metastasis to the central nervous system (CNS), have a poor prognosis [1, 2].”
How did lomustine become standard of care in recurrent glioblastoma?
Weller, M., & Rhun, É. L. (2020) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2020.102029 · Cited by 250
“Procarbazine is another alkylating agent chemically related to temozolomide that has inferior activity in recurrent glioblastoma as a single agent compared with temozolomide [22].”
BackgroundPhase II trial of bevacizumab and erlotinib in patients with recurrent malignant glioma
Sathornsumetee, S., Desjardins, A., Vredenburgh, J. J., McLendon, R. E., Marcello, J. E., Herndon, J. E., Mathe, A., Hamilton, M., Rich, J. N., Norfleet, J. A., et al. (2010) · Neuro-Oncology · doi:10.1093/neuonc/noq099 · Cited by 230
“Previous meta-analyses demonstrated that PFS-6 is an adequate indicator of antitumor benefit for salvage GBM clinical trials.3,4 With Yung et al.28 reporting a PFS-6 of 21% (95% confidence interval [CI], 13%–29”
MethodSelf-citationHasselbalch, B., Lassen, U., Hansen, S., Holmberg, M., Mau‐Sørensen, M., Kosteljanetz, M., Broholm, H., Stockhausen, M., & Poulsen, H. S. (2010) · Neuro-Oncology · doi:10.1093/neuonc/nop063 · Cited by 229
Advances in Glioblastoma Therapy: An Update on Current Approaches
Angom, R. S., Nakka, N. M. R., & Bhattacharya, S. (2023) · Brain Sciences · doi:10.3390/brainsci13111536 · Cited by 251
Groves, M. D., Puduvalli, V. K., Hess, K. R., Jaeckle, K. A., Peterson, P., Yung, W. K. A., & Levin, V. A. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.20.5.1383 · Cited by 229
Self-citationBrandes, A. A., Tosoni, A., Cavallo, G., Bertorelle, R., Gioia, V., Franceschi, E., Biscuola, M., Blatt, V., Crinò, L., & Ermani, M. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6603376 · Cited by 226
“In the three available studies investigating this regimen in this setting, PFS-6 was 21% (Yung et al, 2000) (CI:13– 29%), 18% (Brada et al, 2001) (CI:11–24%), and 24% (Brandes et al, 2002) (CI:14–42%).”
BackgroundInfluentialTemozolomide for high grade glioma
Hart, M. G., Garside, R., Rogers, G., Stein, K., & Grant, R. (2013) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007415.pub2 · Cited by 223
Joensuu, H., Kankaanranta, L., Seppälä, T., Auterinen, I., Kallio, M., Kulvik, M., Laakso, J. T., Vähätalo, J., Kortesniemi, M., Kotiluoto, P., et al. (2003) · Journal of Neuro-Oncology · doi:10.1007/bf02699939 · Cited by 220
“The median progression-free survival of these patients is only about 3 months even when treated with modern chemotherapy agents such as temozolomide [27], and there is no curative therapy available.”
BackgroundStereotactic radiosurgery (SRS)
Combs, S. E., Widmer, V., Thilmann, C., Hof, H., Debus, J., & Schulz–Ertner, D. (2005) · Cancer · doi:10.1002/cncr.21429 · Cited by 217
“After treatment with temozolomide, 6 months progression-free survival rates of 46 – 60% can be found in the literature.(34,35) Surgical resections may be possible in some patients.”
BackgroundIzumoto, S., Tsuboi, A., Oka, Y., Suzuki, T., Hashiba, T., Kagawa, N., Hashimoto, N., Maruno, M., Elisseeva, O. A., Shirakata, T., et al. (2008) · Journal of neurosurgery · doi:10.3171/jns/2008/108/5/0963 · Cited by 215
Hau, P., Jachimczak, P., Schlingensiepen, R., Schulmeyer, F. J., Jauch, T., Steinbrecher, A., Brawanski, A. T., Proescholdt, M. A., Schlaier, J. R., Buchroithner, J., et al. (2007) · Oligonucleotides · doi:10.1089/oli.2006.0053 · Cited by 215
“…and accurate survival data from the literature that clearly distinguish between AA and GBM are available for temozolomide with 42 to 49 (Chang et al., 2004) weeks for recurrent AA and 31.8 (Yung, 2000, Yung et al., 2000) or 32.0 (Theodosopoulos et al., 2001) weeks for recurrent GBM, respectively.”
InfluentialPhotodynamic therapy of high grade glioma – long term survival
Stylli, S. S., Kaye, A. H., MacGregor, L., Howes, M., & Rajendra, P. (2005) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2005.01.006 · Cited by 214
Phase 1 trial of a CpG oligodeoxynucleotide for patients with recurrent glioblastoma1
Carpentier, A. C., Laigle–Donadey, F., Zohar, S., Capelle, L., Béhin, A., Tibi, A., Martin-Duverneuil, N., Sanson, M., Lacomblez, L., Taillibert, S., et al. (2006) · Neuro-Oncology · doi:10.1215/s1522851705000475 · Cited by 212
Optimal role of temozolomide in the treatment of malignant gliomas
Stupp, R., van den Bent, M. J., & Hegi, M. E. (2005) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-005-0047-7 · Cited by 205
Reardon, D. A., Nabors, B., Stupp, R., & Mikkelsen, T. (2008) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.17.8.1225 · Cited by 205
Filippini, G., Falcone, C., Boiardi, A., Broggi, G., Bruzzone, M. G., Caldiroli, D., Farina, R., Farinotti, M., Fariselli, L., Finocchiaro, G., et al. (2007) · Neuro-Oncology · doi:10.1215/15228517-2007-038 · Cited by 204
Reardon, D. A., Desjardins, A., Vredenburgh, J. J., Gururangan, S., Sampson, J. H., Sathornsumetee, S., McLendon, R. E., Herndon, J. E., Marcello, J. E., Norfleet, J. A., et al. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6605412 · Cited by 205
“Yung et al (2000) reported a 6-PFS rate 1987 British Journal of Cancer (2009) 101(12), 1986 – 1994& 2009 Cancer Research UK C li n ic a l S tu d ie s of 21% (95% CI 13 –29) among recurrent GBM patients treated with temozolomide at first recurrence.”
BackgroundMethodSelf-citationCarpentier, A. C., Métellus, P., Ursu, R., Zohar, S., Lafitte, F., Barrié, M., Meng, Y., Richard, M., Parizot, C., Laigle–Donadey, F., et al. (2010) · Neuro-Oncology · doi:10.1093/neuonc/nop047 · Cited by 204
Wu, Q., Qian, W., Sun, X., & Jiang, S. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01362-9 · Cited by 208
Temozolomide in malignant gliomas: current use and future targets
Villano, J. L., Seery, T. E., & Bressler, L. R. (2009) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-009-1050-5 · Cited by 198
“Previously, Yung et al. [ 9 , 10] had demonstrated the beneWt of TMZ in patients with WHO grade III astrocytomas and in patients with GBM in Wrst relapse.”
BackgroundTAPHOORN, M. J. B., Dirven, L., Kanner, A. A., Lavy-Shahaf, G., Weinberg, U., Taillibert, S., Toms, S. A., Honnorat, J., Chen, T. C., Šroubek, J., et al. (2018) · JAMA Oncology · doi:10.1001/jamaoncol.2017.5082 · Cited by 211
“The difference between deterioration-free survival and TTD indicates the importance of disease progression (rather than treatment) as a key event driving HRQoL decline, as suggested by previous studies.(26,27) Moreover, in only 1% of patients, regardless of treatment arm, was a clinically relevant improvement in HRQoL…”
ResultTherapeutic options in recurrent glioblastoma—An update
Seystahl, K., Wick, W., & Weller, M. (2016) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2016.01.018 · Cited by 211
“After approval of TMZ in 1999 for recurrent glioblastoma based on efficacy data of 2 phase II trials and a favorable safety profile [45, 46], nitrosoureas were used less frequently.”
Reardon, D. A., Akabani, G., Coleman, R. E., Friedman, A. H., Friedman, H. S., Herndon, J. E., McLendon, R. E., Pegram, C. N., Provenzale, J. M., Quinn, J. A., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.03.4082 · Cited by 196
Self-citationLessons learned in the development of targeted therapy for malignant gliomas
Omuro, A. M. P., Faivre, S. J., & Raymond, É. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-07-0047 · Cited by 196
“However, phase II data (Table 1) suggested that, although some responses were obtained, the overall efficacy of such compounds in unselected patients was minimal when compared with historical data (2, 3).”
ResultPegylated liposomal doxorubicin‐efficacy in patients with recurrent high‐grade glioma
Hau, P., Fabel, K. S., Baumgart, U., Rümmele, P., Grauer, O. M., Bock, A., Dietmaier, C., Dietmaier, W., Dietrich, J., Dudel, C., et al. (2004) · Cancer · doi:10.1002/cncr.20073 · Cited by 197
“The median OS after treatment with PEG-DOX with or without TAM was 74 weeks, which is equal or superior to the survival durations associated with other second-line chemotherapy regimens.(2,31) As expected, patients with Grade III tumors had a significantly better median OS after diagnosis and exhibited a trend toward…”
ResultTargeted tumor therapy with the TGF-β2 antisense compound AP 12009
SCHLINGENSIEPEN, K., SCHLINGENSIEPEN, R., STEINBRECHER, A., HAU, P., BOGDAHN, U., FISCHERBLASS, B., & JACHIMCZAK, P. (2006) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2005.09.002 · Cited by 195
Peptides for cell-selective drug delivery
Svensen, N., Walton, J. G. A., & Bradley, M. (2012) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2012.02.002 · Cited by 196
Nicholson, H. S., Kretschmar, C. S., Krailo, M., Bernstein, M. L., KADOTA, R. P., Fort, D. W., Friedman, H. S., Harris, M. B., Tedeschi‐Blok, N., Mazewski, C., et al. (2007) · Cancer · doi:10.1002/cncr.22961 · Cited by 195
Self-citationThe role of imaging in the management of progressive glioblastoma
Ryken, T. C., Aygün, N., Morris, J., Schweizer, M. L., Nair, R., Spracklen, C. N., Kalkanis, S. N., & Olson, J. J. (2014) · Journal of Neuro-Oncology · doi:10.1007/s11060-013-1330-0 · Cited by 198
Self-citationPhase 1 Trial of Gefitinib Plus Sirolimus in Adults with Recurrent Malignant Glioma
Reardon, D. A., Quinn, J. A., Vredenburgh, J. J., Gururangan, S., Friedman, A. H., Desjardins, A., Sathornsumetee, S., Herndon, J. E., Dowell, J. M., McLendon, R. E., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2215 · Cited by 190
Self-citationConcerns about anti-angiogenic treatment in patients with glioblastoma multiforme
Verhoeff, J. J. C., van Tellingen, O., Claes, A., Stalpers, L. J. A., Linde, M. E. V., Richel, D. J., Leenders, W. P. J., & van Furth, W. R. (2009) · BMC Cancer · doi:10.1186/1471-2407-9-444 · Cited by 189
“Tumour cells migrate furtively into the surrounding tissue and co-opt existing vasculature. we have shown this in mice bearing orthotopic intracranial tumours treated with TMZ either with or without concomitant anti-angiogenic treatment with vandetanib (ZD6474) [59].”
BackgroundInfluentialTemozolomide: therapeutic limitations in the treatment of adult high-grade gliomas
Chamberlain, M. C. (2010) · Expert Review of Neurotherapeutics · doi:10.1586/ern.10.32 · Cited by 189
Current and future strategies for the treatment of malignant brain tumors
Castro, M. G., Cowen, R. L., Williamson, I., David, A., Jimenez-Dalmaroni, M. J., Yuan, X., Bigliari, A., Williams, J. C., Hu, J., & Lowenstein, P. R. (2003) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(03)00014-7 · Cited by 188
Wilson, M. A., & Schuchter, L. M. (2015) · Cancer treatment and research · doi:10.1007/978-3-319-22539-5_8 · Cited by 191
“Similar to dacarbazine, temozolomide is an alkylating agent, which is FDA-approved in the treatment of glioblastoma [98, 99].”
BackgroundChinot, O. L., Honoré, S., Dufour, H., Barrié, M., Figarella-Branger, D. F., Muracciole, X., Braguer, D., Martin, P., & Grisoli, F. (2001) · Journal of Clinical Oncology · doi:10.1200/jco.2001.19.9.2449 · Cited by 179
Tumor treating fields: A novel treatment modality and its use in brain tumors
Hottinger, A. F., Pacheco, P., & Stupp, R. (2016) · Neuro-Oncology · doi:10.1093/neuonc/now182 · Cited by 177
Momota, H., Nerio, E., & Holland, E. C. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-1042 · Cited by 175
“Temozolomide has become the first choice of chemotherapy for gliomas because of its efficacy, convenience, and tolerability (3, 24, 25).”
BackgroundPhase II Trial of Thalidomide and Carmustine for Patients With Recurrent High-Grade Gliomas
Fine, H. A., Wen, P. Y., Maher, E. A., Viscosi, E., Batchelor, T. T., Lakhani, N. J., Figg, W. D., Purow, B. W., & Borkowf, C. B. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.08.045 · Cited by 173
Imatinib and hydroxyurea in pretreated progressive glioblastoma multiforme: a patient series
Dresemann, G. P. (2005) · Annals of Oncology · doi:10.1093/annonc/mdi317 · Cited by 173
“These results are comparable with published studies in investigational trials with recurrent or relapsed GBM patients [1, 4, 41, 42].”
BackgroundResultRole of a second chemotherapy in recurrent malignant glioma patients who progress on bevacizumab
Lee, E. Q., Norden, A. D., Drappatz, J., Muzikansky, A., Doherty, L. M., LaFrankie, D. C., Ciampa, A. S., Kesari, S., & Wen, P. Y. (2009) · Neuro-Oncology · doi:10.1215/15228517-2009-006 · Cited by 170
Cheng, C.-M., Johnson, S. P., Keir, S. T., Quinn, J. A., Ali‐Osman, F., Szabó, C., Li, H., Salzman, A. L., Dolan, M. E., Modrich, P. L., et al. (2005) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-05-0128 · Cited by 171
Self-citationCloughesy, T. F., Landolfi, J. C., Vogelbaum, M. A., Ostertag, D. G., Elder, J. B., Bloomfield, S. M., Carter, B. S., Chen, C. C., Kalkanis, S. N., Kesari, S., et al. (2018) · Neuro-Oncology · doi:10.1093/neuonc/noy075 · Cited by 170
New (alternative) temozolomide regimens for the treatment of glioma
Wick, W., Platten, M., & Weller, M. (2008) · Neuro-Oncology · doi:10.1215/15228517-2008-078 · Cited by 163
Metadata
- Authors
- Yung, W. K. A., Albright, R. E., Olson, J., Fredericks, R., Fink, K., Prados, M. D., Brada, M., Spence, A., Hohl, R. J., Shapiro, W., Glantz, M., Greenberg, H., Selker, R. G., Vick, N. A., Rampling, R., Friedman, H., Phillips, P., Bruner, J., Yue, N., Osoba, D., Zaknoen, S., & Levin, V. A.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Emory University (US)
- University of Mississippi Medical Center (US)
- The University of Texas Southwestern Medical Center (US)
- University of California, San Francisco (US)
- Royal Marsden NHS Foundation Trust (GB)
- University of Washington (US)
- University of Iowa Hospitals and Clinics (US)
- Barrow Neurological Institute (US)
- Memorial Hospital of Rhode Island (US)
- University of Michigan (US)
- Western Pennsylvania Hospital (US)
- Evanston Hospital (US)
- Beatson West of Scotland Cancer Centre (GB)
- Duke University (US)
- BC Cancer Agency (CA)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Venue
- British Journal of Cancer
- Published
- 2000-09
- Volume
- 83
- Issue
- 5
- Pages
- 588-593
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC2363506
- OpenAlex
- W1977392502
- Cited by
- 929
- References
- 27
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 8 · 2023: 23 · 2022: 19 · 2021: 21 · 2020: 21 · 2019: 20 · 2018: 27 · 2017: 23 · 2016: 31 · 2015: 32 · 2014: 33 · 2013: 38 · 2012: 50
- FWCI
- 21.15
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Health Sciences › Medicine › Oncology › Cancer survivorship and care
- Keywords
- temozolomide, procarbazine, glioblastoma, first relapse, progression-free survival, overall survival, health-related quality of life, alkylating agents, oral chemotherapy, treatment safety
- MeSH terms
- Temozolomide, Adult, Aged, Antineoplastic Agents, Brain Neoplasms, Dacarbazine, Female, Glioblastoma, Humans, Male, Middle Aged, Procarbazine, Prognosis, Quality of Life, Recurrence, Time Factors, Gliosarcoma, Disease-Free Survival, Antineoplastic Agents, Alkylating
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