Randomized Study of Postoperative Radiotherapy and Simultaneous Temozolomide without Adjuvant Chemotherapy for Glioblastoma

Köcher, Martin; Frommolt, Peter; Borberg, Sigrid Klara; Rühl, U; Steingräber, M; Niewald, Marcus; Staar, Susanne; Stuschke, Martin; Becker, Gerd; Fischedick, Arnt-René; Herfarth, Klaus; Grauthoff, H.; Müller, Rolf-Peter

doi:10.1007/s00066-008-1897-0

Cited by 46 publications

(37 citation statements)

References 31 publications

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“…Although adverse effects during radiotherapy/TMZ have been reported in several previous studies, lymphopenia had not been evaluated. The incidence of lymphopenia in our study (68%) is compatible with previous data (68%), 5) although the frequency of CTC grade 4 lymphopenia in the present study was higher than in previous studies. We speculate that the high frequency of low pre lymph in our patients induced the high rate of CTC grade 4 lymphopenia.…”

Section: Discussionsupporting

confidence: 91%

“…10) Lymphopenia was the most frequent adverse effect after radiotherapy/TMZ, and CTC grade 2, 3, and 4 lymphopenia (lymphopenia less than 800/ml, 500/ml, and 200/ml) was observed in 22%, 38%, and 8% (total 68%) of patients, respectively. 5) Severe infections including Pneumocystis jirovecii pneumonia also occur in patients receiving standard-dose TMZ therapy. 9,14) On the other hand, TMZ has the potential ability to enhance immunotherapies in experimental studies, 4,7) and some studies of vaccine-based immunotherapy combined with TMZ have been tried for glioblastoma.…”

Section: Introductionmentioning

confidence: 99%

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Low Peripheral Lymphocyte Count Before Focal Radiotherapy Plus Concomitant Temozolomide Predicts Severe Lymphopenia During Malignant Glioma Treatment

Ishikawa

Yamamoto

Sakamoto

et al. 2010

Neurol. Med. Chir.(Tokyo)

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Malignant glioma patients treated with the golden standard therapy, focal radiotherapy plus concomitant daily temozolomide (radiotherapy/TMZ), often suffer severe lymphopenia. The frequency of severe lymphopenia and its predictors were analyzed by assessing adverse effects including decrease in white blood cell counts, lymphocyte counts, and neutrocyte counts according to the Common Toxicity Criteria version 3.0 (CTC) in 28 consecutive patients with pathologically verified malignant gliomas treated with radiotherapy/TMZ. Eighty-two percent of the patients suffered one or more adverse effects; lymphopenia (68%) was the most frequent adverse effect, with 32% of patients suffering CTC grade 4 lymphopenia. CTC grade 4 lymphopenia was associated with the incidence of other CTC grade 3 or 4 adverse effects and discontinuance of TMZ. Minimal lymphocyte counts during radiotherapy/TMZ and lymphocyte counts before radiotherapy/TMZ showed close linear correlation by linear regression analysis (p º 0.0001, R 2 ＝ 0.569), and the most important predictor for CTC grade 4 lymphopenia was lymphocyte count before radiotherapy/TMZ less than 1200/ml by multivariate analysis (p º 0.0321, Exp ＝ 13.2). Lymphocyte counts before radiotherapy/TMZ of less than 1200/ml predict severe lymphopenia during radiotherapy/TMZ.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Low Peripheral Lymphocyte Count Before Focal Radiotherapy Plus Concomitant Temozolomide Predicts Severe Lymphopenia During Malignant Glioma Treatment

Ishikawa

Yamamoto

Sakamoto

et al. 2010

Neurol. Med. Chir.(Tokyo)

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“…9 However, in that study, the enrollment was stopped due to an unacceptable frequency of toxicity related to the neoadjuvant chemotherapeutic agents. Clinical use of 6 weeks of continuous TMZ often causes Grade 3 or 4 lymphopenia, 7,11 and this was seen in the present study. Some animal studies have indicated that TMZ may enhance antitumor immunity.…”

Section: Discussionsupporting

confidence: 76%

Phase I/IIa trial of fractionated radiotherapy, temozolomide, and autologous formalin-fixed tumor vaccine for newly diagnosed glioblastoma

Ishikawa

Muragakı

Yamamoto

et al. 2014

JNS

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Object Temozolomide (TMZ) may enhance antitumor immunity in patients with glioblastoma multiforme (GBM). In this paper the authors report on a prospective Phase I/IIa clinical trial of fractionated radiotherapy (FRT) concomitant with TMZ therapy, followed by treatment with autologous formalin-fixed tumor vaccine (AFTV) and TMZ maintenance in patients with newly diagnosed GBM. Methods Twenty-four patients (age 16–75 years, Karnofsky Performance Scale score ≥ 60% before initiation of FRT) with newly diagnosed GBM received a total dose of 60 Gy of FRT with daily concurrent TMZ. After a 4-week interval, the patients received 3 AFTV injections and the first course of TMZ maintenance chemotherapy for 5 days, followed by multiple courses of TMZ for 5 days in each 28-day cycle. Results This treatment regimen was well tolerated by all patients. The percentage of patients with progression-free survival (PFS) ≥ 24 months was 33%. The median PFS, median overall survival (OS), and the actuarial 2- and 3-year survival rates of the 24 patients were 8.2 months, 22.2 months, 47%, and 38%, respectively. The median PFS in patients with a delayed-type hypersensitivity (DTH) response after the third AFTV injection (DTH-2) of 10 mm or larger surpassed the median length of follow-up for progression-free patients (29.5 months), which was significantly greater than the median PFS in patients with a smaller DTH-2 response. Conclusions The treatment regimen was well tolerated and resulted in favorable PFS and OS for newly diagnosed GBM patients. Clinical trial registration no.: UMIN000001426 (UMIN clinical trials registry, Japan).

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“…Also, higher PFS rates were observed in the RT + TMZ group in all studies, except for Kocher et al [25], where a lower PFS at 6 months in the RT + TMZ group, as compared to the RT group (55.2 vs. 66.7%) was reported.…”

Section: Resultsmentioning

confidence: 91%

Temozolomide with or without Radiotherapy in Patients with Newly Diagnosed Glioblastoma Multiforme: A Meta-Analysis

2017

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Background/Aim: The current meta-analysis evaluated the survival outcomes of newly diagnosed glioblastoma patients treated with radiotherapy (RT) alone and with RT + temozolomide (TMZ). Methods: Relevant studies were identified by an extensive literature search in Medline, Current Contents and Cochrane databases by 2 independent reviewers using the terms “glioblastoma multiforme/glioblastoma, TMZ, radiation therapy/RT and survival.” Results: Results revealed a median survival of 13.41-19 months in the combined treatment group, as opposed to 7.7-17.1 months in the RT-alone group. Progression-free survival (PFS) was also significantly different between the 2 groups (RT + TMZ, 6.3-13 months; RT-alone, 5-7.6 months). While there was no significant difference in the 6-month survival and 6-month PFS rates between the RT + TMZ and RT groups (pooled OR 0.690; p = 0.057 and OR 0.429, p = 0.052, respectively), the 1-year survival and 1-year PFS rates showed significant difference (OR 0.469; p = 0.030 and OR 0.245, p < 0.001, respectively). Conclusions: Concomitant RT + TMZ is more effective and improves the overall survival and PFS in patients with newly diagnosed glioblastoma.

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Randomized Study of Postoperative Radiotherapy and Simultaneous Temozolomide without Adjuvant Chemotherapy for Glioblastoma

Abstract: After early closure of this trial, a benefit for progression-free survival for simultaneous TMZ radiochemotherapy alone could not be demonstrated. In both arms, salvage therapies were frequently used and probably had a major effect on overall survival.

Cited by 46 publications

References 31 publications

Low Peripheral Lymphocyte Count Before Focal Radiotherapy Plus Concomitant Temozolomide Predicts Severe Lymphopenia During Malignant Glioma Treatment

Low Peripheral Lymphocyte Count Before Focal Radiotherapy Plus Concomitant Temozolomide Predicts Severe Lymphopenia During Malignant Glioma Treatment

Phase I/IIa trial of fractionated radiotherapy, temozolomide, and autologous formalin-fixed tumor vaccine for newly diagnosed glioblastoma

Temozolomide with or without Radiotherapy in Patients with Newly Diagnosed Glioblastoma Multiforme: A Meta-Analysis

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