|
|
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
From the Departments of Medical Oncology and Neurological
Sciences, Azienda Ospedale-University Hospital, Padova; the Department of
Radiochemotherapy, San Raffaele Hospital, Milan; and the Department of Medical
Oncology, Bellaria Hospital, Bologna, Italy.
Address reprint requests to Alba A. Brandes, MD, Department
of Medical Oncology-Direzione, Azienda Ospedale-Universitą Ospedale Busonera,
Via Gattamelata 64, 35100 Padova, Italy; e-mail: aabrandes@unipd.it
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/m2 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.
Presented in part at the 38th Annual Meeting of the American
Society of Clinical Oncology, Orlando, FL, May 18-21, 2002.
© 2004 American Society for Clinical Oncology
Source: http://www.jco.org/cgi/content/abstract/22/9/1598
|
