Randomized, placebo-controlled, phase II study of dasatinib with standard chemo-radiotherapy for newly diagnosed glioblastoma (GBM), NCCTG N0877 (Alliance).
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Le résumé fourni par la source
2013 Background: Dasatinib is a potent oral ATP competitive multi-targeted kinase inhibitor of multiple members of the Src kinase family known to be involved in gliomagenesis, tumor invasion, and radiosensitivity. N0877 is a phase I/randomized phase II trial evaluating the combination of dasatinib, radiation (RT) and temozolomide (TMZ) in newly diagnosed GBM. Methods: Following a 13 patient phase I dose escalation trial which established the MTD and phase II dose of dasatinib to be 150 mg PO daily when given with RT and TMZ, the randomized placebo-controlled phase II portion of the trial was initiated. The study followed a 2:1 randomization procedure with 85% power to detect a hazard ratio of 1.6 or higher in overall survival (OS) between the two arms and a type I error rate of 0.10. Dasatinib or placebo was given orally for 42 days, beginning with the first day of RT (total dose 60 Gy) and first dose of TMZ (75 mg/m2/d). Following a 24 - 42 day rest, patients then received 6 cycles (28 day cycles) of dasatinib or placebo (days 1-28) and TMZ (days 1-5). At the completion of 6 cycles of TMZ + dasatinib/placebo, patients continued on dasatinib/placebo only (28 day cycles) until progressive disease. Results: Data from 187 of 196 patients enrolled were available for analysis. Median follow-up was 12.6m for dasatinib (N = 133 pts), and 14m for placebo (N = 63 pts). There was no significant difference in PFS between dasatinib and placebo (6.7m vs 7.8m, respectively; HR 0.80 favoring placebo, 95% CI 0.57-1.1, p = 0.18) or OS (15.5m vs 20.6m; HR 0.71 favoring placebo, 95% CI 0.46-1.1, p = 0.12). Response rate (CR+PR) was 10.5% for dasatinib and 8.3% in placebo arm (p = 0.77). The overall incidence of grade 3 or higher hematologic toxicity was lower in the dasatinib arm (43.9% vs 68.8%, p = 0.0012) primarily due to lower rates of lymphopenia. Grade 3 or higher non-hematologic toxicities were similar between arms (53.8% vs 41.3%, p = 0.1384). Analysis by MGMT status will be forthcoming. Conclusions: The combination of the Src kinase inhibitor dasatinib with standard RT/TMZ did not improve the outcome of newly diagnosed GBM patients as compared to standard therapy alone. Clinical trial information: NCT00869401.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Randomized, placebo-controlled, phase II study of dasatinib with standard chemo-radiotherapy for newly diagnosed glioblastoma (GBM), NCCTG N0877 (Alliance).
- Date Crossref
- 20/05/2015
- Éditeur
- American Society of Clinical Oncology (ASCO)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Mayo Clinic in Arizona Alliance Statistics and Data Center pays non établi dans la noticeÉtablissement de santé
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Mayo Clinic pays non établi dans la noticeÉtablissement de santé
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East Carolina University pays non établi dans la noticeUniversité ou école supérieure
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Illinois CancerCare pays non établi dans la noticeÉtablissement de santé
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Wake Forest University pays non établi dans la noticeUniversité ou école supérieure
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Jacksonville College pays non établi dans la noticeUniversité ou école supérieure
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WinnMed pays non établi dans la noticeOrganisation à but non lucratif
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Mayo Clinic in Florida pays non établi dans la noticeÉtablissement de santé
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Illinois Cancer Care pays non établi dans la noticeInstitution
Alliance Statistics and Data Center — Mayo Clinic in Arizona, Mayo Clinic et East Carolina University, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.