Palbociclib is not effective for adult patients with recurrent glioblastoma

Jennie WTaylor of neurosurgery at the University of California, San Francisco, USA, has conducted research on the efficacy of recurrent GBM and its pharmacokineticand and pharmacodynamics characteristicsThe results were published online August 2018 in Journal of Neuro-Oncology- From the article chapter
(Ref: Taylor JW, et alJNeurooncol.)2018 Nov;140 (2):477-483doi: 10.1007/s11060-018-2977-3Epub 2018 Aug 27changes in the signaling pathway of CDK4/6-RB are a common cause of cell cycle deregulation of glioblastoma (GBM)Palbociclib is an oral inhibitor of CDK4/6 that causes RB1 phosphorylation and cell cycle stasisJennie WTaylor of neurosurgery at the University of California, San Francisco, USA, has conducted research on the efficacy of recurrent GBM and its pharmacokineticand and pharmacodynamics characteristicsThe results were published online August 2018 in Journal of Neuro-Oncologythe criteria for patients enrolled in this open label, arms and single-drug clinical trials include, 18-year-old GBM or glioblastoma patients, after receiving radiotherapy or promoamine treatment imaging examination confirmed tumor recurrence, through immunohistamytome testing to confirm RB1 level, without limiting the number of chemotherapy occasions, with a KPS status score of 60The patients were divided into two groups, Arm1 patients had surgical indications, the treatment was to give Palbociclib treatment 7 days before surgery to remove the tumor, and continued to use the drug as an adjunct therapy after surgery; The main results of treatment were 6 months of no progression, and the secondary results were drug toxicity reactions, overall survival rates and objective efficiency study included 22 patients, including 6 of them Arm1 and 16 Arm2 The trial was stopped early due to poor efficacy; 95% of assessable patients had progression within 6 months, PFS was 5 days to 142 weeks, the median was 5.14 weeks, and THE OS was 2-274 weeks with a median of 15.4 weeks In terms of safety, 2 patients (10%) had drug side effects of level 3 or above The results of the immunological histology test of histological samples paired before and after treatment showed that the expression of RB1 was inconsistent and there was still a lack of consistent change trend after quantification test results show that the use of single-drug Palbociclib is not an effective treatment for recurrent glioblastoma According to current preclinical studies, Palbociclib's penetration ability to central nerve tissue and local concentration of the drug can meet biologically effective requirements, and the authors believe that some of the reasons for palbociclib ineffectiveness in patients with glioblastoma may be related to previous treatment and bevalcosina resistance However, the treatment of CDK4/6 pathways in the early stages of the course and the simultaneous combination of radiotherapy are still worth exploring further.