Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse
Open accessAbstract
Background Recurrent glioblastoma multiforme (GBM) is resistant to most therapeutic endeavors, with low response rates and survival rarely exceeding six months. There are no clearly established chemotherapeutic regimens and the aim of treatment is palliation with improvement in the quality of life.Patients and methods We report an open-label, uncontrolled, multicenter phase II trial of temozolomide in 138 patients (intent-to-treat [ITT] population) with glioblastoma multiforme at first relapse and a Karnofsky performance status (KPS) > or = 70. One hundred twenty-eight patients were histologically confirmed with GBM or gliosarcoma (GS) by independent central review. Chemotherapy-naïve patients were treated with temozolomide 200 mg/m2/day orally for the first five days of a 28-day cycle. Patients previously treated with nitrosourea-containing adjuvant chemotherapy received 150 mg/m2/day for the first five days of a 28-day cycle. In the absence of grade 3 or 4 toxicity, patients on the 150 mg/m2 dose schedule were eligible for a 200 mg/m2 dose on the next cycle.Results The primary endpoint was six-month progression-free survival assessed with strict radiological and clinical criteria. Secondary endpoints included radiological response and Health-related Quality of Life (HQL). Progression-free survival at six months was 18% (95% confidence interval (CI): 11%-26%) for the eligible-histology population. Median progression-free survival and median overall survival were 2.1 months and 5.4 months, respectively. The six-month survival rate was 46%. The objective response rate (complete response and partial response) determined by independent central review of gadolinium-enhanced magnetic resonance imaging (MRI) scans was 8% for both the ITT and eligible-histology populations, with an additional 43% and 45% of patients, respectively, having stable disease (SD). Objectively assessed response and maintenance of a progression-free status were both associated with HQL benefits (characterized by improvements over baseline in HQL domains). Temozolomide had an acceptable safety profile, with only 9% of therapy cycles requiring a dose reduction due to thrombocytopenia. There was no evidence of cumulative hematologic toxicity.Conclusions Temozolomide demonstrated modest clinical efficacy, with an acceptable safety profile and measurable improvement in quality of life in patients with recurrent GBM. The use of this drug should be explored further in an adjuvant setting and in combination with other agents.
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The average historical TTP is 9.5 ± 1.6 weeks.
“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 [26]
The average historical PFS6 based on the above studies is 15.3 ± 3.8%.
“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 [26]
The average historical OS is 29.3 ± 6 weeks.
“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 [26]
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.
“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 [26]
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BackgroundPhase 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].”
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“These figures compare favorably with previous trials using temozolomide, in which median survival was around six months, and one-year survival was less than 15% (Brada et al., 2001; Yung et al., 2000).”
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“Hematological Thrombocytopenia None 60 (51) 43 (48) 2 28 (24) 30 (34) 3 13 (11) 6 (7) 4 16 (14) 10 (11) Neutropenia None 67 (57) 52 (58) 2 28 (24) 23 (26) 3 7 (6) 8 (9) 4 15 (13) 6 (7) Nonhematological Nausea None 65 (56) 59 (66) 2 47 (40) 29 (33) 3 5 (4) 1 (1) 4 0 0 (0) Vomiting None 68 (58) 56 (63) 2 46 (39) 31 (35)…”
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“These results are comparable with published studies in investigational trials with recurrent or relapsed GBM patients [1, 4, 41, 42].”
BackgroundResultRutkowski, S., Vleeschouwer, S. D., Kaempgen, E., Wolff, J. E. A., Kühl, J., Demaerel, P., Warmuth‐Metz, M., Flamen, P., Calenbergh, F. V., Plets, C., et al. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6602195 · Cited by 171 · see citing works
“The prognosis at time of relapse is even worse (Finlay et al, 1995; Nieder et al, 2000; Brada et al, 2001; Tamber and Rutka, 2003; Rich et al, 2004).”
BackgroundHenriksson, R., Asklund, T., & Poulsen, H. S. (2011) · Journal of Neuro-Oncology · doi:10.1007/s11060-011-0565-x · Cited by 164 · see citing works
“, global, motor dysfunction, emotional function, drowsiness, future uncertainty, and communication deficit, until eventual disease progression [38–40].”
BackgroundSelf-citationSchwarzmaier, H., Eickmeyer, F., von Tempelhoff, W., Fiedler, V. U., Niehoff, H., Ulrich, S. D., Yang, Q., & Ulrich, F. (2006) · European Journal of Radiology · doi:10.1016/j.ejrad.2006.05.010 · Cited by 156 · see citing works
“1 months [6,7].”
BackgroundAdvances in Glioblastoma Multiforme Treatment: New Models for Nanoparticle Therapy
Ozdemir-Kaynak, E., Qutub, A. A., & Yeşil-Çeliktaş, Ö. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00170 · Cited by 155 · see citing works
“In 1999, Temozolomide, the oral chemotherapy drug was granted accelerated approval by the FDA to treat anaplastic astrocytoma (a form of high-grade glioma) (Yung et al., 1999; Brada et al., 2001).”
BackgroundSurvival benefit of Boron neutron capture therapy for recurrent malignant gliomas
Miyatake, S., Kawabata, S., Yokoyama, K., Kuroiwa, T., Michiue, H., Sakurai, Y., Kumada, H., Suzuki, M., Maruhashi, A., Kirihata, M., et al. (2008) · Journal of Neuro-Oncology · doi:10.1007/s11060-008-9699-x · Cited by 154 · see citing works
“In the literature, TMZ has actually shown modest survival benefit at relapse of recurrent GBM [19].”
BackgroundCentral nervous system gliomas
Reni, M., Mazza, E. A., Zanon, S. M., Gatta, G., & Vecht, C. J. (2017) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2017.03.021 · Cited by 151 · see citing works
Boron Neutron Capture Therapy for Newly Diagnosed Glioblastoma
Kawabata, S., Miyatake, S., Kuroiwa, T., Yokoyama, K., Doi, A., Kyoko, I. I. D. A., Miyata, S., Nonoguchi, N., Michiue, H., Takahashi, M., et al. (2009) · Journal of Radiation Research · doi:10.1269/jrr.08043 · Cited by 150 · see citing works
Ardon, H., Gool, S. V., Lopes, I. S., Maes, W., Sciot, R., Wilms, G., Demaerel, P., Bijttebier, P., Claes, L., Goffin, J., et al. (2010) · Journal of Neuro-Oncology · doi:10.1007/s11060-010-0131-y · Cited by 147 · see citing works
“At the time of relapse, the prognosis is even worse and virtually all patients are dead within 18 months after relapse [2–5].”
BackgroundSmall molecule kinase inhibitors in glioblastoma: a systematic review of clinical studies
Hamer, P. C. D. W. (2010) · Neuro-Oncology · doi:10.1093/neuonc/nop068 · Cited by 147 · see citing works
Therapeutic options for recurrent malignant glioma
Niyazi, M., Siefert, A., Schwarz, S. B., Ganswindt, U., Kreth, F.-W., Tonn, J., & Belka, C. (2010) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2010.11.006 · Cited by 145 · see citing works
Norden, A. D., & Wen, P. Y. (2006) · The Neurologist · doi:10.1097/01.nrl.0000250928.26044.47 · Cited by 144 · see citing works
Han, K., Ren, M., Wick, W., Abrey, L. E., Das, A., Jin, J., & Reardon, D. A. (2013) · Neuro-Oncology · doi:10.1093/neuonc/not236 · Cited by 141 · see citing works
Schaich, M. A., Kestel, L., Pfirrmann, M., Robel, K., Illmer, T., Krämer, M., Dill, C., Ehninger, G., Schackert, G., & Krex, D. (2008) · Annals of Oncology · doi:10.1093/annonc/mdn548 · Cited by 133 · see citing works
“It is effective in glioblastoma treatment as shown for recurrent glioblastoma first [4, 5] and, recently, in a prospective randomized trial conducted by the European Organization for Research and Treatment of Cancer (EORTC) and the National Cancer Institute of Canada (NCIC) Clinical Trial Group (CTG), for newly diagno…”
MethodHow effective is BCNU in recurrent glioblastoma in the modern era?
Brandes, A. A., Tosoni, A., Amistà, P., Nicolardi, L., Grosso, D., Berti, F., & Ermani, M. (2004) · Neurology · doi:10.1212/01.wnl.0000140495.33615.ca · Cited by 131 · see citing works
Improved Brain Penetration and Antitumor Efficacy of Temozolomide by Inhibition of ABCB1 and ABCG2
de Gooijer, M. C., de Vries, N. A., Buckle, T., Buil, L. C. M., Beijnen, J. H., Boogerd, W., & van Tellingen, O. (2018) · Neoplasia · doi:10.1016/j.neo.2018.05.001 · Cited by 136 · see citing works
Ananda, S. S., Nowak, A. K., Cher, L., DOWLING, A. J., Brown, C. S. B., Simes, J. R., & Rosenthal, M. A. (2011) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2011.02.026 · Cited by 124 · see citing works
Recent developments in the use of chemotherapy in brain tumours
van den Bent, M. J., Hegi, M. E., & Stupp, R. (2006) · European Journal of Cancer · doi:10.1016/j.ejca.2005.06.031 · Cited by 123 · see citing works
Self-citationKeles, G. E., Lamborn, K. R., Chang, S. M., Prados, M. D., & Berger, M. S. (2004) · Journal of neurosurgery · doi:10.3171/jns.2004.100.1.0041 · Cited by 120 · see citing works
Blood-brain barrier, cytotoxic chemotherapies and glioblastoma
Dréan, A., Goldwirt, L., Verreault, M., Canney, M. S., Schmitt, C., Guehennec, J., Delattre, J., Carpentier, A. C., & Idbaïh, A. (2016) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2016.1202761 · Cited by 119 · see citing works
Reoperation for Recurrent High-Grade Glioma
Hervey‐Jumper, S. L., & Berger, M. S. (2014) · Neurosurgery · doi:10.1227/neu.0000000000000486 · Cited by 117 · see citing works
“After several years of use and initially promising results, temozolomide monotherapy at recurrence led to stability of disease in only 5% of patients.(34) Similar to prior published retrospective studies, theirs found no difference in performance status, with a 9-month survival time after repeat surgery and 15.”
ResultBrandes, A. A., Basso, U., Reni, M., Vastola, F., Tosoni, A., Cavallo, G., Scopece, L., Ferreri, A. J. M., Panucci, M. G., Monfardini, S., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.11.019 · Cited by 114 · see citing works
Tuettenberg, J., Grobholz, R., Korn, T., Wenz, F. K., Erber, R., & Vajkoczy, P. (2004) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-004-0620-5 · Cited by 113 · see citing works
“As the chemotherapeutic drug of choice, we used the alkylating agent temozolomide (TMZ), since it is orally administrable, well tolerated, and already approved and used in a conventional, cyclic manner in recurrent malignant glioma (Brada et al. 2001; Yung et al. 2000; Yung et al. 1999).”
MethodRadiotherapy and radiosensitizers in the treatment of glioblastoma multiforme.
Chang, J. E., Khuntia, D., Robins, H. I., & Mehta, M. P. (2007) · PubMed · Cited by 112 · see citing works
Monitoring temozolomide treatment of low-grade glioma with proton magnetic resonance spectroscopy
Murphy, P. S., Viviers, L., Abson, C., Rowland, I. J., Brada, M., Leach, M. O., & Dzik-Jurasz, A. S. K. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6601593 · Cited by 110 · see citing works
“It is licensed for the treatment of recurrent malignant glioma (glioblastoma multiforme and anaplastic astrocytoma) (Yung et al, 1999, 2000; Brada et al, 2001).”
BackgroundMethodResultSelf-citationThe Role of Topotecan in the Treatment of Brain Metastases
Wong, E. T., & Berkenblit, A. (2004) · The Oncologist · doi:10.1634/theoncologist.9-1-68 · Cited by 107 · see citing works
Das, A., Banik, N. L., Patel, S. J., & Ray, S. K. (2004) · Molecular Cancer · doi:10.1186/1476-4598-3-36 · Cited by 105 · see citing works
“Therefore, the use of this drug should be explored further in an adjuvant setting and in combination with other agents [43].”
BackgroundCurrent Chemotherapy for Glioblastoma
Parney, I. F., & Chang, S. M. (2003) · The Cancer Journal · doi:10.1097/00130404-200305000-00003 · Cited by 104 · see citing works
Kong, D., Lee, J.-I., Kim, J. H., Kim, S. T., Kim, W. S., Suh, Y., Dong, S. M., & Nam, D. (2010) · Neuro-Oncology · doi:10.1093/neuonc/nop030 · Cited by 100 · see citing works
Temozolomide: a milestone in neuro-oncology and beyond?
Mutter, N., & Stupp, R. (2006) · Expert Review of Anticancer Therapy · doi:10.1586/14737140.6.8.1187 · Cited by 102 · see citing works
Self-citationAnaplastic astrocytoma in adults
Stupp, R., Reni, M., Gatta, G., Mazza, E. A., & Vecht, C. J. (2007) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2007.03.003 · Cited by 100 · see citing works
Self-citationDose‐dense temozolomide regimens
Neyns, B., Tosoni, A., Hwu, W., & Reardon, D. A. (2010) · Cancer · doi:10.1002/cncr.25035 · Cited by 98 · see citing works
“increase the cumulative dose of temozolomide over a 28day cycle by approximately 2-fold compared with the standard 5 of 28-day schedule.(2,5,6,30,32-38) Dose-dense”
BackgroundTargeting malignant glioma survival signalling to improve clinical outcomes
Wong, M. L. H., Kaye, A. H., & Hovens, C. M. (2007) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2006.11.005 · Cited by 97 · see citing works
Taal, W., Bromberg, J. E. C., & van den Bent, M. J. (2015) · CNS Oncology · doi:10.2217/cns.15.2 · Cited by 96 · see citing works
Management of malignant glioma: steady progress with multimodal approaches
Ashby, L. S., & Ryken, T. C. (2006) · Neurosurgical FOCUS · doi:10.3171/foc.2006.20.4.3 · Cited by 96 · see citing works
Dendritic Cell Therapy of High‐Grade Gliomas
Gool, S. V., Maes, W., Ardon, H., Verschuere, T., Cauter, S. V., & Vleeschouwer, S. D. (2009) · Brain Pathology · doi:10.1111/j.1750-3639.2009.00316.x · Cited by 94 · see citing works
Mandel, J. J., Yust‐Katz, S., Patel, A. J., Cachia, D., Liu, D., Park, M., Yuan, Y., Kent, T. A., & de Groot, J. (2017) · Neuro-Oncology · doi:10.1093/neuonc/nox144 · Cited by 92 · see citing works
Ernst‐Stecken, A., Ganslandt, O., Lambrecht, U., Sauer, R., & Grabenbauer, G. G. (2006) · Journal of Neuro-Oncology · doi:10.1007/s11060-006-9231-0 · Cited by 91 · see citing works
“RS, particularly for small volume recurrences, and salvage chemotherapy are both widely accepted as reasonable treatment options in case of recurrent highgrade glioma [2–8].”
BackgroundToxicity and efficacy of protracted low dose temozolomide for the treatment of low grade gliomas
Pouratian, N., Gasco, J., Sherman, J. H., Shaffrey, M. E., & Schiff, D. (2006) · Journal of Neuro-Oncology · doi:10.1007/s11060-006-9280-4 · Cited by 90 · see citing works
“It has been shown to be efficacious for the treatment of anaplastic gliomas and glioblastomas [1–3].”
BackgroundState-of-the-art treatment of high-grade brain tumors
Brandes, A. A. (2003) · Seminars in Oncology · doi:10.1053/j.seminoncol.2003.11.028 · Cited by 90 · see citing works
Stereotactically Guided Fractionated Re-irradiation in Recurrent Glioblastoma Multiforme
Combs, S. E., Gutwein, S., Thilmann, C., Huber, P. E., Debus, J., & Schulz–Ertner, D. (2005) · Journal of Neuro-Oncology · doi:10.1007/s11060-004-2463-y · Cited by 87 · see citing works
“2 months in patients treated with temozolomide in recurrent or progressive high-grade glioma [24,30].”
BackgroundCarlson, B. L., Grogan, P. T., Mladek, A. C., Schroeder, M. A., Kitange, G. J., Decker, P. A., Giannini, C., Wu, W., Ballman, K. V., James, C. D., et al. (2009) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2009.04.026 · Cited by 87 · see citing works
Phase 2 study of temozolomide and Caelyx in patients with recurrent glioblastoma multiforme
Chua, S. L. L., Rosenthal, M. A., Wong, S., Ashley, D. M., Woods, A.-M., DOWLING, A. J., & Cher, L. (2004) · Neuro-Oncology · doi:10.1215/s1152851703000188 · Cited by 84 · see citing works
“…by guest on 27 July 2018 This compares with that documented for temozolomide alone in the treatment of recurrent GBM but does not suggest that the combination is more active than single agent temozolomide (Brada et al., 2001; Harris et al., 2000; Stupp, et al., 2001; Yung et al., 1999).”
BackgroundResultInfluentialSarin, H. (2009) · Journal of Translational Medicine · doi:10.1186/1479-5876-7-77 · Cited by 85 · see citing works
“otherapy[8,15,20-27]; and in the treatment of metastatic brain tumors, it remains unclear as to if there is any additional benefit of systemic chemotherapy[9,10,28-31].”
Buckner, J. C., Ballman, K. V., Michalak, J. C., Burton, G. V., Cascino, T. L., Schomberg, P. J., Hawkins, R. B., Scheithauer, B. W., Sandler, H. M., Marks, R. S., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.04.6979 · Cited by 85 · see citing works
Broniscer, A., Chintagumpala, M., Fouladi, M., Krasin, M. J., Koçak, M., Bowers, D. C., Iacono, L. C., Merchant, T. E., Stewart, C. F., Houghton, P. J., et al. (2005) · Journal of Neuro-Oncology · doi:10.1007/s11060-005-7409-5 · Cited by 82 · see citing works
“However, temozolomide activity is more modest in recurrent GBM in adults [8,9].”
BackgroundTemozolomide in Combination With Irinotecan for Treatment of Recurrent Malignant Glioma
Gruber, M. L., & Buster, W. P. (2004) · American Journal of Clinical Oncology · doi:10.1097/01.coc.0000045852.88461.80 · Cited by 80 · see citing works
“A large open-label uncontrolled multicenter phase II trial in 128 patients with recurrent GBM had similar results, with an overall response of 52% (67/128), objective response of 8% (CR 2, PR 8), and 6-month PFS of 18%.(8) Other studies (n 14–73) had an overall response rate (CR PR SD) ranging from 42.”
ResultTreatment options for recurrent high-grade gliomas
Birk, H. S., Han, S. J., & Butowski, N. A. (2016) · CNS Oncology · doi:10.2217/cns-2016-0013 · Cited by 77 · see citing works
Recent developments in the molecular characterization and treatment of oligodendroglial tumors
van den Bent, M. J., Chinot, O. L., & Cairncross, J. G. (2003) · Neuro-Oncology · doi:10.1093/neuonc/5.2.128 · Cited by 78 · see citing works
“In a phase 2 trial, Brada et al. (2001) reported a 6-month progression-free survival rate of 18% and a median progression-free survival and median overall survival of 2.1 and 5.4 months, respectively, in GBM patients who received temozolomide at first relapse.”
BackgroundInfluentialDarkes, M. J. M., Plosker, G. L., & Jarvis, B. (2002) · American Journal of Cancer · doi:10.2165/00024669-200201010-00006 · Cited by 78 · see citing works
Unique biology of gliomas: challenges and opportunities
Watkins, S., & Sontheimer, H. W. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.05.001 · Cited by 76 · see citing works
Warren, K. E., Gururangan, S., Geyer, J. R., McLendon, R. E., Poussaint, T. Y., Wallace, D., Balis, F. M., Berg, S. L., Packer, R. J., Goldman, S., et al. (2011) · Journal of Neuro-Oncology · doi:10.1007/s11060-011-0709-z · Cited by 76 · see citing works
“treated with temozolomide alone, objective response rates were 8–19%, and up to 45% of patients had stable disease [4, 29].”
BackgroundNano-structures mediated co-delivery of therapeutic agents for glioblastoma treatment: A review
Mujokoro, B., Adabi, M., Sadroddiny, E., Adabi, M., & Khosravani, M. (2016) · Materials Science and Engineering C · doi:10.1016/j.msec.2016.07.080 · Cited by 74 · see citing works
Erpolat, Ö. P., Akmansu, M., Göksel, F., Bora, H., Yaman, E., & Buyukberber, S. (2009) · Tumori Journal · doi:10.1177/030089160909500210 · Cited by 74 · see citing works
Bartolomei, M., Mazzetta, C., Handkiewicz-Junak, D., Bodei, L., Rocca, P. A., Grana, C. M., Maira, G., Sturiale, C. L., Villa, G., & Paganelli, G. (2004) · PubMed · Cited by 73 · see citing works
The Future of Glioblastoma Therapy: Synergism of Standard of Care and Immunotherapy
Patel, M. A., Kim, J., Ruzevick, J., Li, G., & Lim, M. K. (2014) · Cancers · doi:10.3390/cancers6041953 · Cited by 72 · see citing works
“Later studies built upon these findings, confirming the moderate clinical response and acceptable safety profile of TMZ in various sub-populations, such as the elderly and those at first-relapse [34,35].”
ResultKong, D., Lee, J.-I., Kim, W. K., Son, M. J., Lim, D. H., Kim, S. H., Park, K., Kim, J. W., Eoh, W., & Nam, D. (2006) · Oncology Reports · doi:10.3892/or.16.5.1117 · Cited by 70 · see citing works
“Since the majority of them are no longer candidates for further irradiation or surgical intervention, considerable efforts have been recently focused in the investigation of new chemotherapeutic agents and treatment schedules for recurrent glioblastoma (1-6).”
Temozolomide, quercetin and cell death in the MOGGCCM astrocytoma cell line
Jakubowicz-Gil, J., Langner, E., Wertel, I., Piersiak, T., & Rzeski, W. (2010) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2010.07.015 · Cited by 70 · see citing works
13-cis-Retinoic acid in the treatment of recurrent glioblastoma multiforme
See, S.-J., Levin, V. A., Yung, W.-K. A., Hess, K. R., & Groves, M. D. (2004) · Neuro-Oncology · doi:10.1215/s1152851703000607 · Cited by 69 · see citing works
“However, studies have shown that improvement or maintenance of healthrelated quality of life issues is associated with objectively assessed responses and PFS in patients with malignant gliomas (Brada et al., 2001; Osoba et al., 2000), which is a further impetus to study cRA.”
BackgroundSalvage therapy in patients with glioblastoma
Hau, P., Baumgart, U., Pfeifer, K., Bock, A., Jauch, T., Dietrich, J., Fabel, K. S., Grauer, O. M., Wismeth, C., Klinkhammer‐Schalke, M., et al. (2003) · Cancer · doi:10.1002/cncr.11845 · Cited by 69 · see citing works
Health-related quality of life in patients with high-grade glioma
Cheng, J., Zhang, X., & Liu, B.-L. (2008) · Neuro-Oncology · doi:10.1215/15228517-2008-050 · Cited by 69 · see citing works
- Authors
- Brada, M., Hoang-Xuan, K., Rampling, R., Dietrich, P.-Y., Dirix, L. Y., Macdonald, D., Heimans, J. J., Zonnenberg, B. A., Bravo-Marques, J. M., Henriksson, R., Stupp, R., Yue, N., Bruner, J., Dugan, M., Rao, S., & Zaknoen, S.
- Affiliations
- Royal Marsden Hospital (GB)
- Beatson West of Scotland Cancer Centre (GB)
- University Hospital of Geneva (CH)
- KU Leuven (BE)
- University Medical Center Utrecht (NL)
- Instituto Português de Oncologia Francisco Gentil (PT)
- University Hospital of Umeå (SE)
- Johns Hopkins University (US)
- The University of Texas MD Anderson Cancer Center (US)
- ORCID
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2001-02
- Volume
- 12
- Issue
- 2
- Pages
- 259-266
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W2125643269
- Cited by
- 372
- References
- 35
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 3 · 2023: 7 · 2022: 3 · 2021: 7 · 2020: 9 · 2019: 4 · 2018: 10 · 2017: 12 · 2016: 15 · 2015: 14 · 2014: 12 · 2013: 11 · 2012: 17
- FWCI
- 10.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- PubMed (publishedVersion)
- reroDoc Digital Library (submittedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- University of California, San Francisco
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Cancer survivorship and care
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Keywords
- temozolomide, recurrent glioblastoma, first relapse, gliosarcoma, progression-free survival, objective response rate, health-related quality of life, thrombocytopenia, chemotherapy toxicity, dose escalation, palliative care, overall survival, Karnofsky performance status
- MeSH terms
- Temozolomide, Adult, Aged, Brain Neoplasms, Dacarbazine, Female, Glioblastoma, Humans, Male, Middle Aged, Neoplasm Recurrence, Local, Prognosis, Quality of Life, Disease-Free Survival, Antineoplastic Agents, Alkylating
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