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Phase
II Trial of Cisplatin Plus Temozolomide, in Recurrent and Progressive Malignant
Glioma Patients
Antonio
Silvani, Marica Eoli,
Andrea Salmaggi,
Elena Lamperti, Elio Maccagnano, Giovanni Broggi, Amerigo Boiardi
Departments of
Neuro-oncology (A.Sil., M.E., A.Sal., E.L., A.B), Neuro-radiology (E.M.),
and Neurosurgery (G.B.), Istituto Nazionale Neurologico 'Carlo Besta',
Milan, Italy.
We
report a phase II trial of cisplatinum and temozolomide (TMZ) combination in
recurrent malignant glioma patients.
The DNA repair protein
O(6)-alkylguanine-DNA alkyltransferase (AGAT) is important in glioblastoma
resistance to alkylating antitumor agents.
In vitro, cisplatin (CDDP)
decreases MGMT activity in a time- and dose-dependent manner.
Thirty-three
recurrent malignant glioma patients (20 GBM-13 AA) were treated at recurrence or
progression with a CDDP and TMZ association.
On days 1 and 2, iv CDDP (40
mg/sqm) was administered.
TMZ (at the dose of 200 mg/sqm) was administered as a
single oral daily-dose on days 2–6 (starting 24 h after the first CDDP dose),
the cycle was repeated every 4 weeks.
All patients had been previously treated
with surgery followed by radiotherapy and CDDP + BCNU chemotherapy.
The primary
endpoint of the study was progression free survival at 6 months (PFS-6).
Secondary endpoints included radiological response and toxicities.
Thirty-three
patients received a total of 113 courses (median 3 range 1–11).
Complete
responses were not observed, partial responses were 18.8% with an additional
39.9% of stable disease.
For the whole group of patients the PFS at 6 and 12
months was 52% and 15% with a median TTP of 33 weeks.
PFS-6 for GBM and
Anaplastic astrocytoma (AA) were 35% and 69%, respectively.
PFS-12 for GBM and
AA were 13.8% and 17.3%, respectively.
Median TTP was 21.3 and 39.5 weeks,
respectively.
The principal toxic effects of the regimen were: neutropenia (5
WHO grade IV), thrombocytopenia (4 WHO grade IV), nausea and vomiting.
Keywords:
chemotherapy, cisplatinum, glioblastoma, O(6)-methylguanine-DNA
methyltransferase, recurrent malignant glioma, temozolomide
Copyright
©
2004 Kluwer Academic Publishers. All rights reserved
Source: http://www.kluweronline.com/article.asp?J=5042&I=108&A=13
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