Phase II study of fixed dose rate gemcitabine as radiosensitizer for newly diagnosed glioblastoma multiforme.
OBJECTIVE
In order to evaluate the activity of gemcitabine as radiosensitizer for newly diagnosed glioblastoma multiforme (GBM), a prospective single-center phase II study was conducted.


METHODS
Eligible patients were required to have histologically proven GBM with evaluable and/or measurable disease after surgery. They were treated by standard cranial irradiation plus concomitant fixed dose rate gemcitabine given intravenously at 175 mg/m(2) weekly for 6 weeks. After chemo-radiotherapy, irrespective of tumor response, patients went on to receive oral temozolomide at 150-200 mg/m(2) for 5 days every 28 days.


RESULTS
Twenty-three patients were enrolled. Median age was 57 years (range 43-72) and median Karnofsky performance status was 90 (range 70-100). Seventeen patients had received subtotal resection of the tumor, while six patients had biopsied-only tumors. Four patients responded to treatment (17.5%) with additional 14 (61%) experiencing stable disease for an overall disease control rate of 78.5%. Median progression-free and overall survival were 6.8 and 10.1 months, respectively. The concomitant radiotherapy-gemcitabine combination was well tolerated and severe adverse events were rare, consisting of grade 3 neutropenia and hypertransaminasemia in two cases each. Twenty patients were assessable for methylguanine methyltransferase (MGMT) promoter methylation, 11 of which were found methylated. In the methylated and unmethylated cohorts, disease control was obtained in 10/11 patients (91%) and 7/9 patients (77.5%), respectively.


CONCLUSIONS
Concomitant radiotherapy-gemcitabine is active and well tolerated in newly diagnosed glioblastoma multiforme. Activity is observed both in tumors with methylated and unmethylated MGMT promoter.
Metro
Giulio
G
Division of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy.
Fabi
Alessandra
A
Mirri
Maria A
MA
Vidiri
Antonello
A
Pace
Andrea
A
Carosi
Mariantonia
M
Russillo
Michelangelo
M
Maschio
Marta
M
Giannarelli
Diana
D
Pellegrini
Domenica
D
Pompili
Alfredo
A
Cognetti
Francesco
F
Carapella
Carmine M
CM
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008745:Methylation; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000093542:Gemcitabine