Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosed glioblastoma.
- Stupp R Centre Hospitalier Universitaire Vaudois and University of Lausanne, Rue du Bugnon 46, Lausanne, Switzerland. roger.stupp@chuv.ch
- Hegi ME
- Neyns B
- Goldbrunner R
- Schlegel U
- Clement PM
- Grabenbauer GG
- Ochsenbein AF
- Simon M
- Dietrich PY
- Pietsch T
- Hicking C
- Tonn JC
- Diserens AC
- Pica A
- Hermisson M
- Krueger S
- Picard M
- Weller M
- 2010-05-05
Published in:
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 2010
Adult
Aged
Antineoplastic Agents, Alkylating
Biopsy, Needle
Brain Neoplasms
Combined Modality Therapy
Confidence Intervals
Dacarbazine
Disease-Free Survival
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
Follow-Up Studies
Glioblastoma
Humans
Immunohistochemistry
Infusions, Intravenous
Kaplan-Meier Estimate
Male
Maximum Tolerated Dose
Middle Aged
Neoplasm Recurrence, Local
Neoplasm Staging
Neurosurgical Procedures
Probability
Radiotherapy, Adjuvant
Radiotherapy, Conformal
Risk Assessment
Snake Venoms
Survival Analysis
Temozolomide
Treatment Outcome
English
PURPOSE
Invasion and migration are key processes of glioblastoma and are tightly linked to tumor recurrence. Integrin inhibition using cilengitide has shown synergy with chemotherapy and radiotherapy in vitro and promising activity in recurrent glioblastoma. This multicenter, phase I/IIa study investigated the efficacy and safety of cilengitide in combination with standard chemoradiotherapy in newly diagnosed glioblastoma.
PATIENTS AND METHODS
Patients (age > or = 18 to < or = 70 years) were treated with cilengitide (500 mg) administered twice weekly intravenously in addition to standard radiotherapy with concomitant and adjuvant temozolomide. Treatment was continued until disease progression or for up to 35 weeks. The primary end point was progression-free survival (PFS) at 6 months.
RESULTS
Fifty-two patients (median age, 57 years; 62% male) were included. Six- and 12-month PFS rates were 69% (95% CI, 54% to 80%) and 33% (95% CI, 21% to 46%). Median PFS was 8 months (95% CI, 6.0 to 10.7 months). Twelve- and 24-month overall survival (OS) rates were 68% (95% CI, 53% to 79%) and 35% (95% CI, 22% to 48%). Median OS was 16.1 months (95% CI, 13.1 to 23.2 months). PFS and OS were longer in patients with tumors with O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation (13.4 and 23.2 months) versus those without MGMT promoter methylation (3.4 and 13.1 months). The combination of cilengitide with temozolomide and radiotherapy was well tolerated, with no additional toxicity. No pharmacokinetic interactions between temozolomide and cilengitide were identified.
CONCLUSION
Compared with historical controls, the addition of concomitant and adjuvant cilengitide to standard chemoradiotherapy demonstrated promising activity in patients with glioblastoma with MGMT promoter methylation.
Invasion and migration are key processes of glioblastoma and are tightly linked to tumor recurrence. Integrin inhibition using cilengitide has shown synergy with chemotherapy and radiotherapy in vitro and promising activity in recurrent glioblastoma. This multicenter, phase I/IIa study investigated the efficacy and safety of cilengitide in combination with standard chemoradiotherapy in newly diagnosed glioblastoma.
PATIENTS AND METHODS
Patients (age > or = 18 to < or = 70 years) were treated with cilengitide (500 mg) administered twice weekly intravenously in addition to standard radiotherapy with concomitant and adjuvant temozolomide. Treatment was continued until disease progression or for up to 35 weeks. The primary end point was progression-free survival (PFS) at 6 months.
RESULTS
Fifty-two patients (median age, 57 years; 62% male) were included. Six- and 12-month PFS rates were 69% (95% CI, 54% to 80%) and 33% (95% CI, 21% to 46%). Median PFS was 8 months (95% CI, 6.0 to 10.7 months). Twelve- and 24-month overall survival (OS) rates were 68% (95% CI, 53% to 79%) and 35% (95% CI, 22% to 48%). Median OS was 16.1 months (95% CI, 13.1 to 23.2 months). PFS and OS were longer in patients with tumors with O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation (13.4 and 23.2 months) versus those without MGMT promoter methylation (3.4 and 13.1 months). The combination of cilengitide with temozolomide and radiotherapy was well tolerated, with no additional toxicity. No pharmacokinetic interactions between temozolomide and cilengitide were identified.
CONCLUSION
Compared with historical controls, the addition of concomitant and adjuvant cilengitide to standard chemoradiotherapy demonstrated promising activity in patients with glioblastoma with MGMT promoter methylation.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1200/JCO.2009.26.6650
- PMID 20439646
- Persistent URL
- https://sonar.ch/global/documents/99874
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