Cited by 929Glioma Diagnosis and TreatmentPARP inhibition in cancer therapyCancer survivorship and care

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A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse

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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·2000·British Journal of Cancer

DOI 10.1054/bjoc.2000.1316PMC PMC2363506

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Abstract

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 European Organization for Research and Treatment of Cancer QLQ-C30: A Quality-of-Life Instrument for Use in International Clinical Trials in Oncology
Aaronson, N. K., Ahmedzai, S., Bergman, B., Bullinger, M., Cull, A., Duez, N. J., Filiberti, A., Flechtner, H., Fleishman, S. B., Haes, J. C. J. M. D., et al. (1993) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/85.5.365 · Cited by 16,005 · cited 1×
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MethodSelf-citation
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MethodSelf-citation
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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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“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).”
BackgroundResult
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Antiangiogenic Therapy and Mechanisms of Tumor Resistance in Malignant Glioma
Rahman, R., Smith, S. J., Rahman, C. V., & Grundy, R. G. (2010) · Journal of Oncology · doi:10.1155/2010/251231 · Cited by 91
“[65] W.”
Method
Phase 2 study of dose-intense temozolomide in recurrent glioblastoma
Norden, A. D., Lesser, G. J., Drappatz, J., Ligon, K. L., Hammond, S. N., Lee, E. Q., Reardon, D., Fadul, C. E., Plotkin, S. R., Batchelor, T. T., et al. (2013) · Neuro-Oncology · doi:10.1093/neuonc/not040 · Cited by 91
“The standard 5-day TMZ regimen is welltolerated in patients with recurrent GBM and achieved a response rate of 19% and 6-month progression-free survival (PFS6) of 21% in the era before TMZ was used in first-line therapy.(6) Resistance to TMZ is mediated in part by O(6)-methylguanine-DNA methyltransferase (MGMT), a DNA…”
Method
Poor-prognosis high-grade gliomas: evolving an evidence-based standard of care
Gupta, T., & Sarin, R. (2002) · The Lancet Oncology · doi:10.1016/s1470-2045(02)00853-7 · Cited by 91
Temozolomide in the treatment of recurrent malignant glioma
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“4 weeks and 60% reported by the trial of temozolomide for patients with GM at first recurrence.(11) The combined response and disease stabilization rate of 55% among patients in the current study with Grade 4 lesions also was similar to the 63% rate reported in a smaller study of temozolomide in patients with newly di…”
BackgroundResultSelf-citation
Toxicity 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
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Background
State-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
Intranasal Delivery of Temozolomide-Conjugated Gold Nanoparticles Functionalized with Anti-EphA3 for Glioblastoma Targeting
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“More recently, the use of the methylating agent, temozolomide, has shown activity in the treatment of recurrent (2, 3) and newly diagnosed malignant glioma (4–6).”
BackgroundSelf-citation
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
“Six month survival after temozolomide treatment at relapse ranged from 46 to 60% [22,25], and 44% after treatment with procarbacine [22].”
Background
Radiosensitizing Effects of Temozolomide Observed in vivo only in a Subset of O6-Methylguanine-DNA Methyltransferase Methylated Glioblastoma Multiforme Xenografts
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Phase 2 study of carboplatin, irinotecan, and bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy
Reardon, D. A., Desjardins, A., Peters, K. B., Vredenburgh, J. J., Gururangan, S., Sampson, J. H., McLendon, R. E., Herndon, J. E., Sykes, A. D., Threatt, S., et al. (2011) · Cancer · doi:10.1002/cncr.26188 · Cited by 86
Self-citation
Antisense Therapeutics for Tumor Treatment: The TGF-beta2 Inhibitor AP 12009 in Clinical Development Against Malignant Tumors
Schlingensiepen, K., Fischer-Blass, B., Schmaus, S., & Ludwig, S. (2007) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-540-71279-4_16 · Cited by 89
Clinical variables serve as prognostic factors in a model for survival from glioblastoma multiforme: an observational study of a cohort of consecutive non-selected patients from a single institution
Michaelsen, S. R., Christensen, I. J., Grunnet, K., Stockhausen, M., Broholm, H., Kosteljanetz, M., & Poulsen, H. S. (2013) · BMC Cancer · doi:10.1186/1471-2407-13-402 · Cited by 87
“The drug is well tolerated with mostly mild to moderate adverse events [7].”
Background
Radiochemotherapy with temozolomide as re-irradiation using high precision fractionated stereotactic radiotherapy (FSRT) in patients with recurrent gliomas
Combs, S. E., Bischof, M., Welzel, T., Hof, H., Oertel, S., Debus, J., & Schulz–Ertner, D. (2008) · Journal of Neuro-Oncology · doi:10.1007/s11060-008-9607-4 · Cited by 86
“Besides neurosurgical resection, which should be evaluated for each patient, chemotherapy is probably the most frequent salvage therapy employed for recurrent malignant gliomas, leading to median survival times of about 20 weeks (20); newer substances, such as the oral alkylating agent TMZ, have increased outcome in p…”
Background
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
“These regimens have reported objective responses but have had minimal impact on survival (Brada et al., 2001; Burton and Prados, 1999; Kapelle et al., 2001; Rosenthal et al., 2000; Wong et al., 1999; Yung et al., 2000).”
Background
Recent progress towards development of effective systemic chemotherapy for the treatment of malignant brain tumors
Sarin, H. (2009) · Journal of Translational Medicine · doi:10.1186/1479-5876-7-77 · Cited by 89
“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].”
Glioblastoma multiforme: an emerging paradigm of anti-VEGF therapy
Reardon, D. A., Wen, P. Y., Desjardins, A., Batchelor, T. T., & Vredenburgh, J. J. (2008) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.8.4.541 · Cited by 87
Phase III Trial of Carmustine and Cisplatin Compared With Carmustine Alone and Standard Radiation Therapy or Accelerated Radiation Therapy in Patients With Glioblastoma Multiforme: North Central Cancer Treatment Group 93-72-52 and Southwest Oncology Group 9503 Trials
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
PCV chemotherapy for recurrent glioblastoma
Schmidt, F., Fischer, J., Herrlinger, U., Dietz, K., DICHGANS, J., & Weller, M. (2006) · Neurology · doi:10.1212/01.wnl.0000197792.73656.c2 · Cited by 84
Salvage temozolomide for prior temozolomide responders
Franceschi, E., Omuro, A. M. P., Lassman, A. B., Demopoulos, A. M., Nolan, C. P., & Abrey, L. E. (2005) · Cancer · doi:10.1002/cncr.21564 · Cited by 83
Role of Apelin/APJ axis in cancer development and progression
Masoumi, J., Jafarzadeh, A., Khorramdelazad, H., Abbasloui, M., Abdolalizadeh, J., & Jamali, N. (2020) · Advances in Medical Sciences · doi:10.1016/j.advms.2020.02.002 · Cited by 83
Temozolomide Combined with Irradiation as Postoperative Treatment of Primary Glioblastoma Multiforme
Combs, S. E., Gutwein, S., Schulz–Ertner, D., van Kampen, M., Thilmann, C., Edler, L., Wannenmacher, M., & Debus, J. (2005) · Strahlentherapie und Onkologie · doi:10.1007/s00066-005-1359-x · Cited by 83
“The efficacy of temozolomide was evaluated in recent phase I [2, 20] and phase II studies [11, 13, 36] focusing on patients with recurrent malignant glioma.”
Background
Diffusely Infiltrative Low-Grade Gliomas in Adults
Lang, F. F., & Gilbert, M. R. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.05.2399 · Cited by 83
Survival benefit of glioblastoma patients after FDA approval of temozolomide concomitant with radiation and bevacizumab: A population-based study
Zhu, P., Du, X. L., Lu, G., & Zhu, J. (2017) · Oncotarget · doi:10.18632/oncotarget.17054 · Cited by 85
“For patients with recurrent GBM prior to FDA approval of bevacizumab (BEV), various therapies had been applied including second craniotomy with or without carmustine implantation (Gliadel wafers), salvage radiation, dosedense TMZ, nitrosoureas, carboplatin, PCV (procarbazine, lomustine and vincristine), etoposide or i…”
Method
Temozolomide after Radiotherapy for Newly Diagnosed High-grade Glioma and Unfavorable Low-grade Glioma in Children
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
“However, temozolomide activity is more modest in recurrent GBM in adults [8,9].”
Background
Phase I study of Gliadel™ wafers plus temozolomide in adults with recurrent supratentorial high-grade gliomas
Gururangan, S., Cokgor, I., Rich, J. N., Edwards, S., Affronti, M. L., Quinn, J. A., Herndon, J. E., Provenzale, J. M., McLendon, R. E., Tourt-Uhlig, S., et al. (2001) · Neuro-Oncology · doi:10.1093/neuonc/3.4.246 · Cited by 82
“The 2 main mechanisms of resistance to TEMO are through mismatch repair protein de ciency and increased production of alkylguanine alkyltransferase (Liu et al., 1996; Wedge et al., 1996; Yung et al., 2000).”
BackgroundSelf-citation
Mesenchymal Migration as a Therapeutic Target in Glioblastoma
Zhong, J., Paul, A., Kellie, S. J., & O’Neill, G. M. (2010) · Journal of Oncology · doi:10.1155/2010/430142 · Cited by 92
“More recently, the use of the oral alkylating drug temozolomide is growing and has become the established adjuvant standard of care because it has good ability to cross the blood brain barrier [144] and has proven to be more beneficial than the traditional chemotherapy agents [145, 146].”
Background
Temozolomide 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
“median progression free survival of 4 weeks was seen in patients with recurrent glioblastoma (GBM).(1) Temozolomide”
BackgroundMethod
Economics of Malignant Gliomas: A Critical Review
Raizer, J. J., Fitzner, K. A., Jacobs, D. I., Bennett, C. L., Liebling, D. B., Luu, T. H., Trifilio, S. M., Grimm, S. A., Fisher, M. J., Haleem, M. S., et al. (2015) · Journal of Oncology Practice · doi:10.1200/jop.2012.000560 · Cited by 79
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
Temozolomide
Darkes, M. J. M., Plosker, G. L., & Jarvis, B. (2002) · American Journal of Cancer · doi:10.2165/00024669-200201010-00006 · Cited by 78
Phase II Trial of Cisplatin Plus Temozolomide, in Recurrent and Progressive Malignant Glioma Patients
Silvani, A., Eoli, M., Salmaggi, A., Lamperti, E., Maccagnano, E., Broggi, G., & Boiardi, A. (2004) · Journal of Neuro-Oncology · doi:10.1023/b:neon.0000013479.64348.69 · Cited by 76
“The amount of toxicity and the disadvantage for the patients from our schedule are comparable or less serious than in many other reported studies [21].”
BackgroundResult
Phase I trial of irinotecan plus temozolomide in adults with recurrent malignant glioma
Reardon, D. A., Quinn, J. A., Rich, J. N., Desjardins, A., Vredenburgh, J. J., Gururangan, S., Sathornsumetee, S., Badruddoja, M., McLendon, R. E., Provenzale, J., et al. (2005) · Cancer · doi:10.1002/cncr.21316 · Cited by 77
“2 Gender Male 23 (59) 50 (74) 73 (68) Female 16 (41) 18 (26) 34 (32) Histology GBM 35 (90) 56 (82) 91 (85) AA 4 (10) 11 (16) 15 (14) AO 0 1 (2) 1 (1) KPS 100 4 (10) 8 (12) 12 (11) 90 15 (39) 25 (37) 40 (37) 80 15 (39) 17 (25) 32 (30) 70 4 (10) 14 (21) 18 (17) 60 1 (2) 4 (6) 5 (5) Time to enrollment in wks Median 39.”
Self-citation
Temozolomide and Other Potential Agents for the Treatment of Glioblastoma Multiforme
Nagasawa, D. T., Chow, F. E., Yew, A. Y., Kim, W. B., Cremer, N., & Yang, I. (2012) · Neurosurgery Clinics of North America · doi:10.1016/j.nec.2012.01.007 · Cited by 76
Treatment-related myelodysplastic syndrome after temozolomide for recurrent high-grade glioma
Su, Y., Chang, M., Chiang, M., & Hsieh, R.-K. (2005) · Journal of Neuro-Oncology · doi:10.1007/s11060-004-2028-0 · Cited by 75
“As noted above, the median survival of patients with recurrent aggressive brain tumor treated with TMZ is less than 2 years [7,16].”
Background
The safety of temozolomide in the treatment of malignancies
Trinh, V. A., Patel, S. P., & Hwu, W. (2009) · Expert Opinion on Drug Safety · doi:10.1517/14740330902918281 · Cited by 75
“In a multi-center Phase II study, TMZ was compared with procarbazine in 225 GBM patients at first relapse [20].”
Method
Whole-Brain Radiation Therapy Plus Concomitant Temozolomide for the Treatment of Brain Metastases From Non–Small-Cell Lung Cancer: A Randomized, Open-Label Phase II Study
Chua, D. T. T., Krzakowski, M. J., CHOUAID, C., Pallotta, M. G., Martinez, J. I., Gottfried, M., Curran, W. J., & Throuvalas, N. (2010) · Clinical Lung Cancer · doi:10.3816/clc.2010.n.022 · Cited by 75
Antitenascin-C monoclonal antibody radioimmunotherapy for malignant glioma patients
Reardon, D. A., Zalutsky, M. R., & Bigner, D. D. (2007) · Expert Review of Anticancer Therapy · doi:10.1586/14737140.7.5.675 · Cited by 75
Adjuvant chemotherapy in the treatment of high grade gliomas
Lonardi, S., Tosoni, A., & Brandes, A. A. (2005) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2004.12.005 · Cited by 75
Temozolomide in Combination With Docetaxel in Patients With Advanced Melanoma: A Phase II Study of the Hellenic Cooperative Oncology Group
Bafaloukos, D. I., Gogas, H., Georgoulias, V., Briassoulis, E., Fountzilas, G., Samantas, E., Kalofonos, C., Skarlos, D., Karabelis, A., & Kosmidis, P. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.20.2.420 · Cited by 75
Nano-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 75
HER1/EGFR tyrosine kinase inhibitors for the treatment of glioblastoma multiforme
Raizer, J. J. (2005) · Journal of Neuro-Oncology · doi:10.1007/s11060-005-0603-7 · Cited by 74
“4 weeks, and an overall survival (OS) at 6 months of 60% [13].”
Safety of intraparenchymal convection-enhanced delivery of cintredekin besudotox in early-phase studies.
Kunwar, S., Sm, C., Prados, Berger, M. S., Sampson, J. H., Croteau, D. J., Sherman, J. W., Ay, G., Vs, S., Dul, J. L., et al. (2006) · PubMed · Cited by 74
Combined treatment of glioblastoma patients with locoregional pre-targeted 90Y-biotin radioimmunotherapy and temozolomide.
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
Health related quality of life assessment methodology and reported outcomes in randomised controlled trials of primary brain cancer patients
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Hypofractionated radiotherapy for elderly or younger low-performance status glioblastoma patients: outcome and prognostic factors
Chang, E. L., Yi, W. S., Allen, P. K., Levin, V. A., Sawaya, R. A., & Maor, M. H. (2003) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/s0360-3016(02)04522-4 · Cited by 73
Self-citation
Temozolomide With or Without Radiotherapy in Melanoma With Unresectable Brain Metastases
Hofmann, M. A., Kiecker, F., Wurm, R. E., Schlenger, L., Budach, V., Sterry, W., & Trefzer, U. (2005) · Journal of Neuro-Oncology · doi:10.1007/s11060-005-2914-0 · Cited by 72
“Temozolomide is known to have efficacy in various solid brain tumors and highly resistant malignancies such as anaplastic astrocytoma or glioblastoma [5, 6 ].”
Background
A meta-analysis of bevacizumab alone and in combination with irinotecan in the treatment of patients with recurrent glioblastoma multiforme
Zhang, G., Huang, S., & Wang, Z. (2012) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2011.12.028 · Cited by 72
The Future of Glioblastoma Therapy: Synergism of Standard of Care and Immunotherapy
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“0063) [32,33].”
A pilot study of metronomic temozolomide treatment in patients with recurrent temozolomide-refractory glioblastoma
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“It should be administered at a regular interval in current protocol, giving treatment-free period to avoid the dose-limiting toxicity like non-cumulative myelosuppression (17).”
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Background
Neurological complications of chemotherapy to the central nervous system
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A new schedule of fotemustine in temozolomide-pretreated patients with relapsing glioblastoma
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Background
Disruption of the EF-2 kinase/Hsp90 protein complex: a possible mechanism to inhibit glioblastoma by geldanamycin.
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“It is currently in Phase I/II trials in recurrent GBM in various combinations with TMZ, imatinib or sirolimus (NCT00821080).”
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Procarbazine as Adjunctive Therapy for Treatment of Dogs with Presumptive Antemortem Diagnosis of Granulomatous Meningoencephalomyelitis: 21 Cases (1998–2004)
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Health-related quality of life in patients with high-grade glioma
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NRG oncology RTOG 0625: a randomized phase II trial of bevacizumab with either irinotecan or dose-dense temozolomide in recurrent glioblastoma
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Practical problems with the collection and interpretation of serial quality of life assessments in patients with malignant glioma
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“The American Society of Clinical Oncology have suggested that quality of life should be a primary endpoint in any Phase III study [1] and increasing numbers of studies have utilised health related quality of life to assess the effect of new treatments on patient well-being [2, 3 ].”
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Evidence and context of use for contrast enhancement as a surrogate of disease burden and treatment response in malignant glioma
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Improved survival of glioblastoma patients treated at academic and high-volume facilities: a hospital-based study from the National Cancer Database
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Impact of Chromosome 1p Status in Response of Oligodendroglioma to Temozolomide: Preliminary Results
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Changes in neurocognitive functioning and quality of life in adult patients with brain tumors treated with radiotherapy
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“Tumor progression obviously impact quality of life and cognitive function: in a phase II trial in patients with glioblastoma multiforme at first relapse [87], the authors demonstrated that freedom from disease progression was associated with maintenance of health-related QOL, regardless of treatment received.”
Background
Phase 2 study of BCNU and temozolomide for recurrent glioblastoma multiforme: North American Brain Tumor Consortium study
Prados, M. D., Yung, W. K. A., Fine, H. A., Greenberg, H. S., Junck, L., Chang, S. M., Nicholas, M. K., Robins, H. I., Mehta, M. P., Fink, K., et al. (2004) · Neuro-Oncology · doi:10.1215/s1152851703000309 · Cited by 67
“A randomized phase 2 study comparing temozolomide with procarbazine in the setting of recurrent GBM resulted in a PFS at 6 months of 21% for patients treated with temozolomide compared to 8% for those treated with procarbazine (Yung et al., 2000).”
BackgroundSelf-citation
Standard Therapy for Glioblastoma- A Review of Where We Are
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Poly(ADP‐ribose) polymerase inhibitor increases growth inhibition and reduces G2/M cell accumulation induced by temozolomide in malignant glioma cells
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“…recently demonstrated good single-agent activity and acceptable safety profile in phase II and III clinical trials for the treatment of recurrent high-grade gliomas (Bower et al., 1997; Paulsen et al., 1999; Yung et al., 1999, 2000; Osoba et al., 2000a, 2000b; Brada et al., 2001; Macdonald, 2001).”
Background
Phase II trial of preirradiation and concurrent temozolomide in patients with newly diagnosed anaplastic oligodendrogliomas and mixed anaplastic oligoastrocytomas: RTOG BR0131
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“the treatment of recurrent glioblastoma showed poor efficacy of procarbazine [126].”
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“During the late 1990s and early 2000, temozolomide was used either at the time of recurrence or after the completion of upfront cranial radiation.(18) Nevertheless, our final result of 9% (resection group) and 12% (biopsy group) improvement in the hazard of dying due to chemotherapy was in accordance with that obtaine…”
Result
Prognostic Significance of O6-Methylguanine-DNA Methyltransferase Protein Expression in Patients with Recurrent Glioblastoma Treated with Temozolomide
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Tanshinone-IIA-Based Analogues of Imidazole Alkaloid Act as Potent Inhibitors To Block Breast Cancer Invasion and Metastasis in Vivo
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“In recurrent GBM, using temozolomide, response rates of 5% and 6-month progression-free survival of 21% have been reported.(5,6) Therefore, effective salvage therapies for patients with GBM are needed.”
Background
A rapid and systematic review of the effectiveness of temozolomide for the treatment of recurrent malignant glioma
Dinnes, J., Cave, C., Huang, S., & Milne, R. (2002) · British Journal of Cancer · doi:10.1038/sj.bjc.6600135 · Cited by 63
“Eight full reports of six studies were identified for inclusion in the main review (Dinnes et al, 2001).”
BackgroundMethodInfluential
Advances in the management of glioblastoma: the role of temozolomide and MGMT testing
Nagpal, S., Thomas, & Recht (2012) · Clinical Pharmacology Advances and Applications · doi:10.2147/cpaa.s26586 · Cited by 62
“The US study enrolled 225 patients and compared TMZ with procarbazine, another oral agent that was being used frequently in patients with recurrent GB multiforme.(30) Progression free survival was 12.”
BackgroundMethod
Drug Review: Safety and Efficacy of Bevacizumab for Glioblastoma and Other Brain Tumors
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“Although an analysis of TTD in this study is hampered by the amount of missing data, our finding that HRQoL deterioration was most profound at progression, which has also been found in previous studies [26,27], supports the assumption that predominantly tumour growth affects HRQoL and not treatment [28].”
Multi‐institutional phase II study of temozolomide administered twice daily in the treatment of recurrent high‐grade gliomas
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BackgroundMethodInfluential
Triple-drug Therapy With Bevacizumab, Irinotecan, and Temozolomide Plus Tumor Treating Fields for Recurrent Glioblastoma: A Retrospective Study
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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)
ORCID: Yung, W K A
Olson, J
Prados, M D
Glantz, M
Friedman, H
Levin, V A
Venue: British Journal of Cancer
Publisher: Springer Science and Business Media LLC
Published: 2000-09
Volume: 83
Issue: 5
Pages: 588-593
ISSN: 0007-0920 (ISSN-L)
1532-1827
DOI: 10.1054/bjoc.2000.1316
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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A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse

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