Open-Label Phase II Evaluation of Imatinib in Primary Inoperable or Incompletely Resected and Recurrent Glioblastoma
| Autor: | Lisa Sautter, Ralf Hofheinz, Frederik Wenz, Andreas Hochhaus, Jochen Tuettenberg, Frank A. Giordano, Christoph Groden, Mario Grimm, Peter Vajkoczy, Kirsten Schmieder |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Oncology
Adult Male Cancer Research medicine.medical_specialty medicine.medical_treatment Biopsy ECOG Performance Status Antineoplastic Agents 03 medical and health sciences 0302 clinical medicine Glioma Internal medicine Clinical endpoint medicine Humans 030212 general & internal medicine ddc:610 Protein Kinase Inhibitors Aged Postoperative Care medicine.diagnostic_test business.industry Common Terminology Criteria for Adverse Events Imatinib General Medicine Middle Aged medicine.disease Prognosis Combined Modality Therapy Radiation therapy Treatment Outcome Tumor progression 030220 oncology & carcinogenesis Retreatment Disease Progression Imatinib Mesylate Female Neoplasm Recurrence Local business Glioblastoma medicine.drug Follow-Up Studies |
| Zdroj: | Oncology. 98(1) |
| ISSN: | 1423-0232 |
| Popis: | Purpose:Preclinical studies indicated that imatinib may have single-agent activity in glioblastoma through inhibition of tyrosine kinase activity and also that it might enhance the efficacy of radiotherapy. We therefore sought to investigate clinical efficacy in patients with newly diagnosed and recurrent glioblastoma in combination with radiotherapy. Methods: We conducted a nonrandomized, 2-arm, open-label phase II trial including patients aged 18 years or older with an ECOG performance status of 0–2 that were either newly diagnosed (arm A) with a measurable tumor (i.e., after incomplete resection or biopsy) or that were diagnosed with progression of a glioblastoma after initial therapy (arm B). Patients in arm A received 600 mg/day imatinib in combination with hypofractionated radiotherapy (2.5 Gy per fraction, 22 fractions). Patients in arm B received 600 mg/day imatinib alone or in combination with re-irradiation at various doses. In case tumor progression occurred, CCNU was added (2 cycles, 100 mg/m2) to imatinib. The primary end point was progression-free survival (PFS). The secondary end point was safety, defined as per Common Terminology Criteria for Adverse Events (version 2.0). Overall survival (OS) was analyzed as an exploratory end point. Results: Fifty-one patients were enrolled, of which 19 were included in arm A and 32 in arm B. The median follow-up was 4 (0.5–30) months in arm A and 6.5 (0.3–51.5) months in arm B. The median PFS was 2.8 months (95% CI 0–8.7) in arm A and 2.1 months (95% CI 0–11.8) in arm B. The median OS was 5.0 (0.8–30) months (95% CI 0–24.1) in arm A and 6.5 (0.3–51.5) months (95% CI 0–32.5) in arm B. The major grade 3 events were seizure (present in 17 patients), pneumonia (11 patients), and vigilance decrease (7 patients). Conclusions: Imatinib showed no measurable activity in patients with newly diagnosed or recurrent glioblastoma. |
| Databáze: | OpenAIRE |
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