First-line chemotherapy with cisplatin plus fractionated temozolomide in recurrent glioblastoma multiforme

A phase II study of the Gruppo Italiano Cooperativo di Neuro-Oncologia

Alba A. Brandes, Umberto Basso, Michele Reni, Francesca Vastola, Alicia Tosoni, Giovanna Cavallo, Luciano Scopece, Andres J. Ferreri, Maria G. Panucci, Silvio Monfardini, Mario Ermani

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Purpose: Cisplatin and temozolomide (TMZ) are active in glioblastoma multiforme (GBM), with different profiles of toxicity. A bid regimen of TMZ achieves a strong inhibition of O6-alkylguanine DNA-alkyl transferase (AGAT), and cisplatin reduces AGAT activity in vitro, suggesting a possible synergic interaction. The primary end point of the present multicenter phase II study was progression-free survival (PFS) at 6 months (PFS-6); secondary end points included response, toxicity, and overall survival. Patients and Methods: Chemotherapy-naive patients with GBM who experienced disease recurrence or progression after surgery and standard radiotherapy were eligible. Chemotherapy cycles consisted of cisplatin 75 mg/m2 on day 1, TMZ 130 mg/m 2 bolus followed by nine doses of 70 mg/m2 every 12 hours (total of 5 days) from day 2 every 4 weeks. In the absence of hematologic toxicity, TMZ was escalated to 1,000 mg/m2 in 5 days. Results: A total of 50 patients (median age, 53.4 years; range, 27 to 70 years; median Karnofsky performance status, 80; range, 60 to 100) were accrued in the study. PFS-6 was 34% (95% CI, 23% to 50%), and PFS-12 was 4% (95% CI, 0.3% to 16%). Median PFS was 18.4 weeks (95% CI, 13 to 25.9 weeks). Among 49 assessable patients, one complete response and nine partial responses were obtained, with an overall response rate of 20.4% (95% CI, 7.7% to 33%). Among 203 treatment cycles delivered, the most common grade 3 or grade 4 events included granulocytopenia in 7.9% of cycles, thrombocytopenia in 4%, and neurologic toxicity in three patients (6%). Conclusion: The new cisplatin plus bid TMZ regimen appears active in chemotherapy-naive patients with recurrent GBM and incurs an acceptable toxicity.

Original languageEnglish
Pages (from-to)1598-1604
Number of pages7
JournalJournal of Clinical Oncology
Volume22
Issue number9
DOIs
Publication statusPublished - 2004

Fingerprint

temozolomide
Glioblastoma
Cisplatin
Disease-Free Survival
Drug Therapy
Transferases
Karnofsky Performance Status
Agranulocytosis
DNA
Nervous System
Radiotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

First-line chemotherapy with cisplatin plus fractionated temozolomide in recurrent glioblastoma multiforme : A phase II study of the Gruppo Italiano Cooperativo di Neuro-Oncologia. / Brandes, Alba A.; Basso, Umberto; Reni, Michele; Vastola, Francesca; Tosoni, Alicia; Cavallo, Giovanna; Scopece, Luciano; Ferreri, Andres J.; Panucci, Maria G.; Monfardini, Silvio; Ermani, Mario.

In: Journal of Clinical Oncology, Vol. 22, No. 9, 2004, p. 1598-1604.

Research output: Contribution to journalArticle

Brandes, Alba A. ; Basso, Umberto ; Reni, Michele ; Vastola, Francesca ; Tosoni, Alicia ; Cavallo, Giovanna ; Scopece, Luciano ; Ferreri, Andres J. ; Panucci, Maria G. ; Monfardini, Silvio ; Ermani, Mario. / First-line chemotherapy with cisplatin plus fractionated temozolomide in recurrent glioblastoma multiforme : A phase II study of the Gruppo Italiano Cooperativo di Neuro-Oncologia. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 9. pp. 1598-1604.
@article{214bf0cf589143b4b0bf0857636c41cd,
title = "First-line chemotherapy with cisplatin plus fractionated temozolomide in recurrent glioblastoma multiforme: A phase II study of the Gruppo Italiano Cooperativo di Neuro-Oncologia",
abstract = "Purpose: Cisplatin and temozolomide (TMZ) are active in glioblastoma multiforme (GBM), with different profiles of toxicity. A bid regimen of TMZ achieves a strong inhibition of O6-alkylguanine DNA-alkyl transferase (AGAT), and cisplatin reduces AGAT activity in vitro, suggesting a possible synergic interaction. The primary end point of the present multicenter phase II study was progression-free survival (PFS) at 6 months (PFS-6); secondary end points included response, toxicity, and overall survival. Patients and Methods: Chemotherapy-naive patients with GBM who experienced disease recurrence or progression after surgery and standard radiotherapy were eligible. Chemotherapy cycles consisted of cisplatin 75 mg/m2 on day 1, TMZ 130 mg/m 2 bolus followed by nine doses of 70 mg/m2 every 12 hours (total of 5 days) from day 2 every 4 weeks. In the absence of hematologic toxicity, TMZ was escalated to 1,000 mg/m2 in 5 days. Results: A total of 50 patients (median age, 53.4 years; range, 27 to 70 years; median Karnofsky performance status, 80; range, 60 to 100) were accrued in the study. PFS-6 was 34{\%} (95{\%} CI, 23{\%} to 50{\%}), and PFS-12 was 4{\%} (95{\%} CI, 0.3{\%} to 16{\%}). Median PFS was 18.4 weeks (95{\%} CI, 13 to 25.9 weeks). Among 49 assessable patients, one complete response and nine partial responses were obtained, with an overall response rate of 20.4{\%} (95{\%} CI, 7.7{\%} to 33{\%}). Among 203 treatment cycles delivered, the most common grade 3 or grade 4 events included granulocytopenia in 7.9{\%} of cycles, thrombocytopenia in 4{\%}, and neurologic toxicity in three patients (6{\%}). Conclusion: The new cisplatin plus bid TMZ regimen appears active in chemotherapy-naive patients with recurrent GBM and incurs an acceptable toxicity.",
author = "Brandes, {Alba A.} and Umberto Basso and Michele Reni and Francesca Vastola and Alicia Tosoni and Giovanna Cavallo and Luciano Scopece and Ferreri, {Andres J.} and Panucci, {Maria G.} and Silvio Monfardini and Mario Ermani",
year = "2004",
doi = "10.1200/JCO.2004.11.019",
language = "English",
volume = "22",
pages = "1598--1604",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "9",

}

TY - JOUR

T1 - First-line chemotherapy with cisplatin plus fractionated temozolomide in recurrent glioblastoma multiforme

T2 - A phase II study of the Gruppo Italiano Cooperativo di Neuro-Oncologia

AU - Brandes, Alba A.

AU - Basso, Umberto

AU - Reni, Michele

AU - Vastola, Francesca

AU - Tosoni, Alicia

AU - Cavallo, Giovanna

AU - Scopece, Luciano

AU - Ferreri, Andres J.

AU - Panucci, Maria G.

AU - Monfardini, Silvio

AU - Ermani, Mario

PY - 2004

Y1 - 2004

N2 - Purpose: Cisplatin and temozolomide (TMZ) are active in glioblastoma multiforme (GBM), with different profiles of toxicity. A bid regimen of TMZ achieves a strong inhibition of O6-alkylguanine DNA-alkyl transferase (AGAT), and cisplatin reduces AGAT activity in vitro, suggesting a possible synergic interaction. The primary end point of the present multicenter phase II study was progression-free survival (PFS) at 6 months (PFS-6); secondary end points included response, toxicity, and overall survival. Patients and Methods: Chemotherapy-naive patients with GBM who experienced disease recurrence or progression after surgery and standard radiotherapy were eligible. Chemotherapy cycles consisted of cisplatin 75 mg/m2 on day 1, TMZ 130 mg/m 2 bolus followed by nine doses of 70 mg/m2 every 12 hours (total of 5 days) from day 2 every 4 weeks. In the absence of hematologic toxicity, TMZ was escalated to 1,000 mg/m2 in 5 days. Results: A total of 50 patients (median age, 53.4 years; range, 27 to 70 years; median Karnofsky performance status, 80; range, 60 to 100) were accrued in the study. PFS-6 was 34% (95% CI, 23% to 50%), and PFS-12 was 4% (95% CI, 0.3% to 16%). Median PFS was 18.4 weeks (95% CI, 13 to 25.9 weeks). Among 49 assessable patients, one complete response and nine partial responses were obtained, with an overall response rate of 20.4% (95% CI, 7.7% to 33%). Among 203 treatment cycles delivered, the most common grade 3 or grade 4 events included granulocytopenia in 7.9% of cycles, thrombocytopenia in 4%, and neurologic toxicity in three patients (6%). Conclusion: The new cisplatin plus bid TMZ regimen appears active in chemotherapy-naive patients with recurrent GBM and incurs an acceptable toxicity.

AB - Purpose: Cisplatin and temozolomide (TMZ) are active in glioblastoma multiforme (GBM), with different profiles of toxicity. A bid regimen of TMZ achieves a strong inhibition of O6-alkylguanine DNA-alkyl transferase (AGAT), and cisplatin reduces AGAT activity in vitro, suggesting a possible synergic interaction. The primary end point of the present multicenter phase II study was progression-free survival (PFS) at 6 months (PFS-6); secondary end points included response, toxicity, and overall survival. Patients and Methods: Chemotherapy-naive patients with GBM who experienced disease recurrence or progression after surgery and standard radiotherapy were eligible. Chemotherapy cycles consisted of cisplatin 75 mg/m2 on day 1, TMZ 130 mg/m 2 bolus followed by nine doses of 70 mg/m2 every 12 hours (total of 5 days) from day 2 every 4 weeks. In the absence of hematologic toxicity, TMZ was escalated to 1,000 mg/m2 in 5 days. Results: A total of 50 patients (median age, 53.4 years; range, 27 to 70 years; median Karnofsky performance status, 80; range, 60 to 100) were accrued in the study. PFS-6 was 34% (95% CI, 23% to 50%), and PFS-12 was 4% (95% CI, 0.3% to 16%). Median PFS was 18.4 weeks (95% CI, 13 to 25.9 weeks). Among 49 assessable patients, one complete response and nine partial responses were obtained, with an overall response rate of 20.4% (95% CI, 7.7% to 33%). Among 203 treatment cycles delivered, the most common grade 3 or grade 4 events included granulocytopenia in 7.9% of cycles, thrombocytopenia in 4%, and neurologic toxicity in three patients (6%). Conclusion: The new cisplatin plus bid TMZ regimen appears active in chemotherapy-naive patients with recurrent GBM and incurs an acceptable toxicity.

UR - http://www.scopus.com/inward/record.url?scp=2442717967&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2442717967&partnerID=8YFLogxK

U2 - 10.1200/JCO.2004.11.019

DO - 10.1200/JCO.2004.11.019

M3 - Article

VL - 22

SP - 1598

EP - 1604

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 9

ER -