Phase I-II trial of imatinib mesylate (Gleevec; STI571) in treatment of recurrent oligodendroglioma and mixed oligoastrocytoma. North central cancer treatment group study N0272 (ALLIANCE/NCCTG)
| Autor: | Merrill J. Egorin, Sonja Anderson, Kurt A. Jaeckle, Jann N. Sarkaria, Patrick J. Flynn, Paul D. Brown, Caterina Giannini, Erin Twohy, Jan C. Buckner, Jesse G. Dixon, Robert B. Jenkins, John Schwerkoske, Evanthia Galanis |
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| Přispěvatelé: | Jaeckle K.A., Anderson S.K., Twohy E.L., Dixon J.G., Giannini C., Jenkins R., Egorin M.J., Sarkaria J.N., Brown P.D., Flynn P.J., Schwerkoske J., Buckner J.C., Galanis E. |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Oncology
Male Cancer Research Cohort Studies Antineoplastic Agent 0302 clinical medicine Tissue Distribution Alliance PDGF Middle Aged Prognosis Cancer treatment Survival Rate Neurology 030220 oncology & carcinogenesis Imatinib Mesylate Female Case-Control Studie medicine.drug Human medicine.medical_specialty Maximum Tolerated Dose Prognosi Data_MISCELLANEOUS Oligodendroglioma Antineoplastic Agents Astrocytoma N0272 Article Mixed oligoastrocytoma Follow-Up Studie 03 medical and health sciences Internal medicine medicine Humans Survival rate NCCTG Group study business.industry Imatinib medicine.disease Imatinib mesylate Phase i ii imatinib Case-Control Studies Neurology (clinical) Cohort Studie Neoplasm Recurrence Local business 030217 neurology & neurosurgery Follow-Up Studies |
| Zdroj: | J Neurooncol |
| Popis: | Purpose: To evaluate the pharmacokinetics and efficacy of imatinib in patients with recurrent oligodendroglial tumors. Methods: Patients with progressive WHO grade II-III recurrent tumors after prior RT and chemotherapy were eligible. A phase I dose-escalation study was conducted for patients on enzyme-inducing anticonvulsants (EIAC). A phase II study for non-EIAC patients utilized a fixed dose of 600mg/D. Primary efficacy endpoint was 6-month progression-free survival (PFS6). A 2-stage design was utilized, with 90% power to detect PFS6 increase from 25 to 45%. Results: In the Phase I, maximum tolerated dose was not reached at 1200mg/D. For phase II patients, overall PFS6 was 33% and median PFS 4.0months (95% CI 2.1, 5.7). Median overall survival (OS) was longer in imatinib-treated patients compared with controls (16.6 vs. 8.0months; HR = 0.64, 95% CI 0.41,1.0, p = 0.049), and longer in patients with 1p/19q-codeleted tumors (19.2 vs. 6.2months, HR = 0.43, 95% CI 0.21,0.89, p = 0.019). Confirmed response rate was 3.9% (PR = 1; REGR = 1), with stable disease observed in 52.9%. At 600mg/D, mean steady-state imatinib plasma concentration was 2513ng/ml (95% CI 1831,3195). Grade 3–4 adverse events (hematologic, fatigue, GI, hypophosphatemia, or hemorrhage) occurred in 61%. Conclusions: Although adequate plasma levels were achieved, the observed PFS6 of 33% did not reach our pre-defined threshold for success. Although OS was longer in imatinib-treated patients than controls, this finding would require forward validation in a larger cohort. Imatinib might show greater activity in a population enriched for PDGF-dependent pathway activation in tumor tissue. |
| Databáze: | OpenAIRE |
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