9 januari 2011: Deze studie en commentaar van arts-bioloog drs. E. Valstar herzien omdat Temodal inmiddels standaard medicijn is bij hersentumoren. In 2005 berichtten we al over.

We hebben inmiddels de resultaten van onderstaande studie na 5 jaar toegevoegd aan de artikelen over Temodal. Zie onder chemo en Temozolomide in deze artikelenreeks d.d. 16 maart 2009.

29 augustus 2005: Bronnen: Ned Tijdschr Geneeskd. 2005 Jun 18;149(25):1393-9. en Pediatr Blood Cancer. 2005 Jul 26; en Ann Oncol. 2005 Jun;16(6):942-9. Epub 2005 May 3.

Van arts-bioloog drs. E. Valstar kregen we de opmerking dat een fase III studie waarin temozolomide werd gebruikt naast bestraling de 2-jaars overleving significant hoger werd. Ons eerdere commentaar dat er geen fase III studie zou zijn is dus niet waar. We beginnen dan ook met het abstract van deze fase III studie onder deze inleiding die we ook aangepast hebben.
Patiënten met inoperabele hersentumoren horen steeds vaker dat zij als behandeling een chemokuur met temozolomide krijgen aangeboden.

De door ons gevonden recente studieresultaten geven o.i. niet echt spectaculaire resultaten van het gebruik van temozolomide bij hersentumoren, hoewel een fase III studie uit mei 2005 wel een verschil in twee jaars overleving laat zien van 10% naar 28%. Hoewel een mediane overleving van 12,1 maanden naar 14,5 maanden weer niet erg spectaculair oogt. Een alternatief voor chemo bij hersentumoren kan dr. Burzysnki zijn die echt bewezen heeft en aan het bewijzen is veel en veel betere resultaten te behalen met zijn antineoplaston therapie bij o.a. hersentumoren dan welke andere behandeling dan ook maar deze moet volledig zelf betaald worden. Hier enkele abstracts van recente studies met temozolomide bij hersentumoren. Oordeelt u zelf en leest u dan ook over dr. Burzynski of over effect van PSK = medicinale paddestoelen bij hersentumoren.

1: N Engl J Med. 2005 Mar 10;352(10):987-96.

Comment in:
N Engl J Med. 2005 Jun 2;352(22):2350-3; author reply 2350-3.
N Engl J Med. 2005 Jun 2;352(22):2350-3; author reply 2350-3.
N Engl J Med. 2005 Jun 2;352(22):2350-3; author reply 2350-3.
N Engl J Med. 2005 Mar 10;352(10):1036-8.

Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma

. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group.

Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. roger.stupp@chuv.hospvd.ch

BACKGROUND: Glioblastoma, the most common primary brain tumor in adults, is usually rapidly fatal. The current standard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with radiotherapy plus temozolomide, given concomitantly with and after radiotherapy, in terms of efficacy and safety. METHODS: Patients with newly diagnosed, histologically confirmed glioblastoma were randomly assigned to receive radiotherapy alone (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival. RESULTS: A total of 573 patients from 85 centers underwent randomization. The median age was 56 years, and 84 percent of patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone. The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P<0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologic toxic effects in 7 percent of patients. CONCLUSIONS: The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity. Copyright 2005 Massachusetts Medical Society. Publication Types:
Clinical Trial
Clinical Trial, Phase III
Multicenter Study
Randomized Controlled Trial

PMID: 15758009 [PubMed - indexed for MEDLINE]

Ned Tijdschr Geneeskd. 2005 Jun 18;149(25):1393-9

Comment in:
Ned Tijdschr Geneeskd. 2005 Jun 18;149(25):1376-8. [Favourable result for temozolomide in recurrent high-grade glioma] [Article in Dutch] Taal W, van der Rijt CD, Sillevis Smitt PA, Kros JM, van Heuvel I, Eting RH, van den Bent MJ. Erasmus MC, locatie Daniel den Hoed Oncologisch Centrum, Postbus 5201, Rotterdam. w.taal@erasmusmc.nl OBJECTIVE: To describe the results of the treatment of recurrent glioma with temozolomide. DESIGN: Retrospective. METHOD: This study evaluated 77 patients with a recurrent high-grade glioma who from August 1997-December 2003 were treated with temozolomide (150-200 mg/m2/day for 5 days per 28-day cycle) following surgery and radiotherapy at the Daniel den Hoed Oncology Centre of the Erasmus MC, Rotterdam, the Netherlands. The patients were divided into 4 groups depending on histology and chemotherapy history. RESULTS: 15 patients received temozolomide for a recurrent anaplastic oligodendroglioma or mixed oligo-astrocytoma. The response in this group was 80% and after 12 months in 47% of the patients there was no disease progression. 35 patients underwent second-line chemotherapy with temozolomide after earlier chemotherapy with procarbazine, lomustine and vincristine for recurrent anaplastic oligodendroglioma or mixed oligo-astrocytoma. Response was 26% and after 12 months in 15% of patients there was still no disease progression. 14 patients were treated with temozolomide for a recurrent anaplastic astrocytoma with a response of 35% and after 12 months in 8% of these patients there was no disease progression. Of the 13 patients with a recurrent glioblastoma who were treated with temozolomide 16% responded and after 6 and 12 months 21% were still free from progression. Temozolomide was well-tolerated: 2 patients had to stop because of probable side effects. CONCLUSION. Temozolomide has an acceptable safety profile and may be regarded as the preferred treatment for recurrent anaplastic gliomas after radiotherapy. There is only a limited role for temozolomide in the treatment of recurrent glioblastoma. PMID: 15997692 [PubMed - indexed for MEDLINE] Ned Tijdschr Geneeskd. 2005 Jun 18;149(25):1376-8. Comment on: Ned Tijdschr Geneeskd. 2005 Jun 18;149(25):1379-85. Ned Tijdschr Geneeskd. 2005 Jun 18;149(25):1393-9. [Temozolomide in patients with a glioblastoma multiforme: new developments] [Article in Dutch] Bromberg JE, Postma TJ. Erasmus MC, locatie Daniel den Hoed Oncologisch Centrum, afd. Neurooncologie, Postbus 5201, Rotterdam. j.bromberg@erasmusmc.nl There are new scientific data concerning the treatment of patients with glioblastoma multiforme with concomitant and adjuvant temozolomide following surgery and radiotherapy. Patients have an improved survival rate, especially if they also have a methylated promoter of the methylguanine-DNA-methyltransferase (MGMT) gene. It is advisable to consider treating young patients with primary glioblastoma multiforme who are in good condition with concomitant and adjuvant temozolomide. Efficacy of temozolomide in recurrent glioblastoma multiforme is limited. Publication Types: Comment PMID: 15997689 [PubMed - indexed for MEDLINE] Pediatr Blood Cancer. 2005 Jul 26;

Temozolomide in resistant or relapsed pediatric solid tumors.
De Sio L, Milano GM, Castellano A, Jenkner A, Fidani P, Dominici C, Donfrancesco A. Division and Laboratory of Oncology, Department of Pediatric of Pediatric Oncology Oncology-Haematology and Blood Bank Service, Bambino Gesu Children's Hospital, Rome, Italy.

PURPOSE: We report the off-label study aimed at investigating the use of temozolomide (TMZ) as single agent in relapsed or resistant pediatric solid tumors. The drug was administered at the dose of 215 mg/m(2)/day x 5 days or 180 mg/m(2)/day x 5 days in patients with prior craniospinal irradiation (CSI) or autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS: Fifty two patients, median age 127.6 months, with resistant or relapsed solid tumors were enrolled. Tumor types were: neuroblastoma (NB; n = 17), medulloblastoma (MB; 8), brain stem glioma (BSG; 8), extraosseous Ewing's sarcoma/peripheral neuroectodermal tumor (EOES; 4), Ewing's sarcoma (ES; 4), anaplastic astrocytoma (AA; 3), rhabdomyosarcoma (RMS; 2), ependymoma (EP; 2), cerebral primitive neuroectodermal tumor (cPNET; 2), hepatocarcinoma (HC; 1), and osteosarcoma (OS; 1). All patients were pre-treated. Two outpatient courses were administered, with a median of 4.8 courses/pt. RESULTS: Objective response-rate (CR + PR + MR) in our series was 13.4% (1.9% CR, 3.8% PR, and 7.7% MR), SD occurred in 38.4% of patients and 48% had PD. The median survival was 7.8 months (range 1-37) and median time to progression was 3.4 months (range 1-20); these data were significantly correlated with histology and previous nitrosureas administration in multivariate analysis. Haematological toxicity grade 3-4 (mainly thrombocytopenia) was observed in 21.4% of administered courses, nausea was reported in 3.1% and respiratory distress in 0.7%. CONCLUSION: Oral TMZ was well tolerated in children with resistant or relapsed solid tumors and showed activity in NB and CNS tumours refractory to standard chemotherapy. (c) 2005 Wiley-Liss, Inc.

PMID: 16047361 [PubMed - as supplied by publisher] Ann Oncol. 2005 Jun;16(6):942-9. Epub 2005 May 3.

Neoadjuvant phase II multicentre study of new agents in patients with malignant glioma after minimal surgery. Report of a cohort of 187 patients treated with temozolomide.

Brada M, Ashley S, Dowe A, Gonsalves A, Huchet A, Pesce G, Reni M, Saran F, Wharram B, Wilkins M, Wilkins P. Academic Unit of Radiotherapy and Oncology, The Institute of Cancer Research, London. michael.brada@icr.ac.uk

BACKGROUND: The aim of this study was to assess the efficacy of new agents in patients with malignant glioma in a neoadjuvant setting not confounded by surgery. The first study of neoadjuvant temozolomide aimed to provide a benchmark for future evaluation of new treatments. PATIENTS AND METHODS: This was a multicentre phase II study of chemotherapy in patients with histologically verified glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA) who had undergone biopsy alone. Patients were planned to receive two cycles of temozolomide at 200 mg/m(2) orally daily for 5 days at a 28-day interval prior to radiotherapy. Response was assessed by two central observers on pre- and post-chemotherapy enhanced scans using bi-dimensional criteria and as progression-free survival (PFS) at the time of second assessment prior to radiotherapy. Withdrawal from the study due to worsening clinical condition was, in the absence of second imaging, assessed as progressive disease. Survival and quality of life (QOL) were secondary endpoints. RESULTS: Between August 1999 and June 2002, 188 patients from 15 UK and two Italian centres were entered into the study and 187 were analysed. Overall, 162 patients were assessable for response; seven had partial and 25 had minimal response. The objective response rate was 20% [95% confidence interval (CI) 14-26%] and PFS prior to commencing radiotherapy was 64% (95% CI 57-72%). The median survival was 10 months, and 1-year survival 41%. The median survival of responders was 16 months compared to 3 months in patients with progressive disease (P <0.001 on multivariate analysis). CONCLUSION: The phase II study design of primary chemotherapy in patients with malignant glioma following biopsy alone is feasible and provides as objective a method of assessment of efficacy as is currently available. The baseline data on temozolomide provide a benchmark for assessment of efficacy of other agents and combinations.

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