A retrospective pooled analysis of response patterns and risk factors in recurrent malignant glioma patients receiving a nitrosourea-based chemotherapy

Alessandro Paccapelo, Ivan Lolli, Maria Grazia Fabrini, Giovanni Silvano, Beatrice Detti, Franco Perrone, Giuseppina Savio, Erminio Bonizzoni, Tania Perrone, Silvia Scoccianti

Research output: Contribution to journalArticle

Abstract

Background: At recurrence the use of nitrosoureas is widely-used as a therapeutic option for glioblastoma (GBM) patients. The efficacy of fotemustine (FTM) has been demonstrated in phase II clinical trials; however, these papers report a wide range of progression-free-survival (PFS-6m) rates, ranging from 21% to 52%. We investigated whether FTM could have a different response pattern in respect to time to adjuvant temozolomide failure, or whether specific independent risk factors could be responsible for the wide range of response rates observed. Methods: Recurrent GBM patients have been treated with fotemustine 75-100mg/sqm at day 1, 8, 15 and after 4/5 weeks of rest with 100 mg/sqm every 21 days. Patients were stratified in 4 groups according to time to temozolomide failure: before starting (B0), during the first 6 months (B1), after more than 6 months of therapy (B2), and after a treatment-free interval (B3). Primary endpoint was PFS-6m. A multivariable analysis was performed to identify whether gender, time after radiotherapy, second surgery and number of TMZ cycles could be independent predictors of the clinical benefit to FTM treatment. Results: 163 recurrent GBM patients were included in the analysis. PFS-6m rates for the B0, B1, B2 and B3 groups were 25%, 28%, 31.1% and 43.8%, respectively. The probability of disease control was higher in patients with a longer time after radiotherapy (p=0.0161) and in those who had undergone a second surgery (p=0.0306). Conclusions: FTM is confirmed as a valuable therapeutic option for patients with recurrent GBM and was active in all study patient groups. Time after the completion of radiotherapy and second surgery are independent treatment-related risk factors that were predictive of clinical benefit.

Original languageEnglish
Pages (from-to)90
Number of pages1
JournalJournal of Translational Medicine
DOIs
Publication statusAccepted/In press - May 14 2012

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fotemustine
Chemotherapy
Glioma
temozolomide
Radiotherapy
Drug Therapy
Glioblastoma
Surgery
Disease control
Therapeutics
Phase II Clinical Trials
Disease-Free Survival

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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A retrospective pooled analysis of response patterns and risk factors in recurrent malignant glioma patients receiving a nitrosourea-based chemotherapy. / Paccapelo, Alessandro; Lolli, Ivan; Fabrini, Maria Grazia; Silvano, Giovanni; Detti, Beatrice; Perrone, Franco; Savio, Giuseppina; Bonizzoni, Erminio; Perrone, Tania; Scoccianti, Silvia.

In: Journal of Translational Medicine, 14.05.2012, p. 90.

Research output: Contribution to journalArticle

Paccapelo, Alessandro ; Lolli, Ivan ; Fabrini, Maria Grazia ; Silvano, Giovanni ; Detti, Beatrice ; Perrone, Franco ; Savio, Giuseppina ; Bonizzoni, Erminio ; Perrone, Tania ; Scoccianti, Silvia. / A retrospective pooled analysis of response patterns and risk factors in recurrent malignant glioma patients receiving a nitrosourea-based chemotherapy. In: Journal of Translational Medicine. 2012 ; pp. 90.
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abstract = "Background: At recurrence the use of nitrosoureas is widely-used as a therapeutic option for glioblastoma (GBM) patients. The efficacy of fotemustine (FTM) has been demonstrated in phase II clinical trials; however, these papers report a wide range of progression-free-survival (PFS-6m) rates, ranging from 21{\%} to 52{\%}. We investigated whether FTM could have a different response pattern in respect to time to adjuvant temozolomide failure, or whether specific independent risk factors could be responsible for the wide range of response rates observed. Methods: Recurrent GBM patients have been treated with fotemustine 75-100mg/sqm at day 1, 8, 15 and after 4/5 weeks of rest with 100 mg/sqm every 21 days. Patients were stratified in 4 groups according to time to temozolomide failure: before starting (B0), during the first 6 months (B1), after more than 6 months of therapy (B2), and after a treatment-free interval (B3). Primary endpoint was PFS-6m. A multivariable analysis was performed to identify whether gender, time after radiotherapy, second surgery and number of TMZ cycles could be independent predictors of the clinical benefit to FTM treatment. Results: 163 recurrent GBM patients were included in the analysis. PFS-6m rates for the B0, B1, B2 and B3 groups were 25{\%}, 28{\%}, 31.1{\%} and 43.8{\%}, respectively. The probability of disease control was higher in patients with a longer time after radiotherapy (p=0.0161) and in those who had undergone a second surgery (p=0.0306). Conclusions: FTM is confirmed as a valuable therapeutic option for patients with recurrent GBM and was active in all study patient groups. Time after the completion of radiotherapy and second surgery are independent treatment-related risk factors that were predictive of clinical benefit.",
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T1 - A retrospective pooled analysis of response patterns and risk factors in recurrent malignant glioma patients receiving a nitrosourea-based chemotherapy

AU - Paccapelo, Alessandro

AU - Lolli, Ivan

AU - Fabrini, Maria Grazia

AU - Silvano, Giovanni

AU - Detti, Beatrice

AU - Perrone, Franco

AU - Savio, Giuseppina

AU - Bonizzoni, Erminio

AU - Perrone, Tania

AU - Scoccianti, Silvia

PY - 2012/5/14

Y1 - 2012/5/14

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AB - Background: At recurrence the use of nitrosoureas is widely-used as a therapeutic option for glioblastoma (GBM) patients. The efficacy of fotemustine (FTM) has been demonstrated in phase II clinical trials; however, these papers report a wide range of progression-free-survival (PFS-6m) rates, ranging from 21% to 52%. We investigated whether FTM could have a different response pattern in respect to time to adjuvant temozolomide failure, or whether specific independent risk factors could be responsible for the wide range of response rates observed. Methods: Recurrent GBM patients have been treated with fotemustine 75-100mg/sqm at day 1, 8, 15 and after 4/5 weeks of rest with 100 mg/sqm every 21 days. Patients were stratified in 4 groups according to time to temozolomide failure: before starting (B0), during the first 6 months (B1), after more than 6 months of therapy (B2), and after a treatment-free interval (B3). Primary endpoint was PFS-6m. A multivariable analysis was performed to identify whether gender, time after radiotherapy, second surgery and number of TMZ cycles could be independent predictors of the clinical benefit to FTM treatment. Results: 163 recurrent GBM patients were included in the analysis. PFS-6m rates for the B0, B1, B2 and B3 groups were 25%, 28%, 31.1% and 43.8%, respectively. The probability of disease control was higher in patients with a longer time after radiotherapy (p=0.0161) and in those who had undergone a second surgery (p=0.0306). Conclusions: FTM is confirmed as a valuable therapeutic option for patients with recurrent GBM and was active in all study patient groups. Time after the completion of radiotherapy and second surgery are independent treatment-related risk factors that were predictive of clinical benefit.

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