To determine the maximum tolerated dose (MTD) of tipifarnib in combination with conventional radiotherapy for patients with newly diagnosed glioblastoma. The MTD was evaluated in three patient ...cohorts, stratified based on concurrent use of enzyme-inducing antiepileptic drugs (EIAED) or concurrent treatment with temozolomide (TMZ): Group A: patients not receiving EIAED and not receiving TMZ; Group A-TMZ: patients not receiving EIAED and receiving treatment with TMZ; Group B: any patients receiving EIAED but not TMZ.
After diagnostic surgery or biopsy, treatment with tipifarnib started 5 to 9 days before initiating radiotherapy, twice daily, in 4-week cycles using discontinuous dosing (21 out of 28 days), until toxicity or progression. For Group A-TMZ, patients also received TMZ daily during radiotherapy and then standard 5/28 days dosing after radiotherapy. Dose-limiting toxicity (DLT) was determined over the first 10 weeks of therapy for all cohorts.
Fifty-one patients were enrolled for MTD determination: 10 patients in Group A, 21 patients in Group A-TMZ, and 20 patients in Group B. In the Group A and Group A-TMZ cohorts, patients achieved the intended MTD of 300 mg twice daily (bid) with DLTs including rash and fatigue. For Group B, the MTD was determined as 300 mg bid, half the expected dose. The DLTs included rash and one intracranial hemorrhage. Thirteen of the 20 patients evaluated in Group A-TMZ were alive at 1 year.
Tipifarnib is well tolerated at 300 mg bid given discontinuously (21/28 days) in 4-week cycles, concurrently with standard chemo/radiotherapy. A Phase II study should evaluate the efficacy of tipifarnib with radiation and TMZ in patients with newly diagnosed glioblastoma and not receiving EIAED.
Introduction
Patients with recurrent high-grade gliomas (HGG) have limited treatment options. HGG utilize the PD-1 pathway to evade immune responses. Checkpoint inhibitors have demonstrated safety ...and clinical activity in patients with recurrent glioblastoma. We explored the efficacy of nivolumab in recurrent HGG with a primary objective of progression free survival (PFS) and overall survival (OS).
Methods
We retrospectively analyzed HGG patients treated with nivolumab in our institution. We included patients with advanced HGG who received nivolumab at their oncologist’s decision. Patients received nivolumab 3 mg/kg every 2 weeks until confirmed progression, intolerable toxicity, death, or physician decision. Radiographic assessments were performed every 8 weeks.
Results
Between April 2015 and October 2017, 50 HGG patients received nivolumab. 43 patients received nivolumab with bevacizumab. 44 patients were bevacizumab refractory and 7 patients received nivolumab monotherapy. All had received prior radiation and chemotherapy. 39 adverse events (AEs) were noted most commonly fatigue (16%) and constipation (10%). 4 (8%) patients experienced grade 3–4 AEs. 36 (72%) patients experienced stable disease (SD) at the 2-month assessment. Median duration of SD was 4.3 months (5.1 months in the bevacizumab naïve, 3.8 months in the bevacizumab refractory). Median PFS was 4.3 months (95% CI 3.5–5.3); median OS was 6.5 months (95% CI 6.0–8.8).
Conclusion
Treatment with nivolumab therapy was associated with a manageable safety profile. In a subset of patients, there was disease stabilization in heavily pre-treated recurrent HGG.
e14020
Background: This phase II trial was performed to assess the efficacy of Border Zone Stereotactic Radiosurgery (BZ-SRS) with bevacizumab by overall survival (OS) in patients with recurrent or ...progressive glioblastoma (GBM) following conventional upfront management. Methods: Patients with histologically confirmed GBM with recurrent disease, received prior first-line treatment with surgery/biopsy, fractionated radiotherapy and chemotherapy, ≥ 2 months since completion of radiotherapy and eligible for SRS were enrolled. Bevacizumab 10mg/kg was given one day before, day 14 and then every 14 days until disease progression. 1 to 14 days before BZ-SRS procedure, patients underwent standard brain MRI /MRS. MRS with measurement of choline-to-N-acetyl aspartate index (CNI) area ≥ 3 was targeted for SRS using standard MRI targeting. Results: From 2015-2017, sixteen patients were enrolled. The median age was 62 (range, 48-74Y). 3 of 16 (0.188) participants experienced grade 2 unacceptable toxicity. The median OS was 11.73 months. No survival difference is seen compared with the University of Pittsburgh historical controls. PFS-6 and OS-6 were 31.2% (p=0.00294) and 81.2%(p= 0.058), respectively. Of 13 evaluable for best response: 1 complete response (p=0.077), 4 partial responses (p=0.308), 7 stable disease (p=0.538), and 1 progressed disease (p=0.077). 11 of 16 participants had MRS scans with an estimated probability that MRS changes a treatment plan of 0 (0,0.285). Conclusions: BZ-SRS with bevacizumab was feasible and well tolerated. There is no significant survival benefit using BZ-SRS with bevacizumab compared to historical controls. Secondary analysis revealed a trend toward improved PFS-6, but not OS-6. MRS scans did not result in any changes in SRS treatment plans. Clinical trial information: NCT02120287 .
Oligodendrogliomas are therapy-responsive tumors, which have better prognosis compared to their astrocytic counterparts. The goal of treatment in such cases is not only prolongation of the patients' ...survival, but maintaining high neurologic functioning and quality of life. Traditionally, after maximal surgical resection fractionated radiation therapy was given. However, prospective randomized trials comparing irradiation alone and its combination with chemotherapy demonstrated strong impact of the latter on prolongation of overall survival in 1p/19q co-deleted anaplastic and "high-risk" low-grade gliomas. In such cases the median survival of patients is well beyond a decade. The optimal chemotherapy regimen (PCV or temozolomide) remains an active clinical trial question, which may be resolved after completion of the ongoing phase III CODEL study (clinicaltrials.gov identifier NCT00887146). Additional investigations should also refine further the prognostic and predictive role of molecular markers in oligodendroglial tumors.
Targeted drug therapy for meningiomas Norden, Andrew D; Drappatz, Jan; Wen, Patrick Y
Neurosurgical focus,
2007, Letnik:
23, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Although advances in surgery, radiation therapy, and stereotactic radiosurgery have significantly improved the treatment of meningiomas, there remains an important subset of patients whose tumors are ...refractory to conventional therapy. Treatment with traditional chemotherapeutic agents has provided minimal benefit. In this review, the role of targeted molecular therapies for recurrent or progressive meningiomas is discussed.
We report a case of hypertrophic olivary degeneration due to cerebellar surgery for a low-grade tumor. A 27-year-old female presented with right-sided paresthesias and intermittent leg paresis ...following a right cerebellar resection of a tumor 2 weeks prior. One month later, her symptoms remained stable while her neurological examination demonstrated slight right hemi-body hypoesthesia and subtle appendicular ataxia in her right upper extremity. An MRI scan revealed a hypertrophied left anterolateral medulla with increased T2 signal and no diffusion abnormality. The T2 hyperintensity and hypertrophy slowly resolved and she clinically improved without further intervention. Hypertrophic olivary degeneration may be mistaken for tumor progression, post-operative vasculopathy or granulation tissue and should be considered in patients undergoing cerebellar surgery.
OBJECTIVE To quantify size and localization differences between tumors presenting with seizures vs nonseizure neurological symptoms. DESIGN Retrospective imaging survey. We performed magnetic ...resonance imaging–based morphometric analysis and nonparametric mapping in patients with brain tumors. SETTING University-affiliated teaching hospital. PATIENTS OR OTHER PARTICIPANTS One hundred twenty-four patients with newly diagnosed supratentorial glial tumors. MAIN OUTCOME MEASURES Volumetric and mapping methods were used to evaluate differences in size and location of the tumors in patients who presented with seizures as compared with patients who presented with other symptoms. RESULTS In high-grade gliomas, tumors presenting with seizures were smaller than tumors presenting with other neurological symptoms, whereas in low-grade gliomas, tumors presenting with seizures were larger. Tumor location maps revealed that in high-grade gliomas, deep-seated tumors in the pericallosal regions were more likely to present with nonseizure neurological symptoms. In low-grade gliomas, tumors of the temporal lobe as well as the insular region were more likely to present with seizures. CONCLUSIONS The influence of size and location of the tumors on their propensity to cause seizures varies with the grade of the tumor. In high-grade gliomas, rapidly growing tumors, particularly those situated in deeper structures, present with non–seizure-related symptoms. In low-grade gliomas, lesions in the temporal lobe or the insula grow large without other symptoms and eventually cause seizures. Quantitative image analysis allows for the mapping of regions in each group that are more or less susceptible to seizures.Arch Neurol. 2010;67(3):336-342-->
Purpose
Recurrent glioblastoma is universally fatal with limited effective treatment options. The aim of this phase 2 study of Border Zone SRS plus bevacizumab was to evaluate OS in patients with ...recurrent GBM.
Methods
Patients with histologically confirmed GBM with recurrent disease who had received prior first-line treatment with fractionated radiotherapy and chemotherapy and eligible for SRS were enrolled. Bevacizumab 10 mg/kg was given day -1, day 14, and then every 14 days until disease progression. 1–14 days before BZ-SRS procedure, patients underwent brain MRI /MRS. MRS with measurement of choline-to-N-acetyl aspartate index (CNI) area ≥ 3 was targeted for SRS.
Results
From 2015–2017, sixteen of planned 40 patients were enrolled. The median age was 62 (range, 48–74Y). 3/16 (0.188) participants experienced grade 2 toxicity. No AREs were reported. The mOS was 11.73 months compared to 8.74 months (P = 0.324) from date of SRS for the BZ-SRS and institutional historical controls, respectively. PFS-6 and OS-6 were 31.2% (p = 0.00294) and 81.2%(p = 0.058), respectively. Of 13 evaluable for best response: 1 CR (p = 0.077), 4 PR (p = 0.308), 7 SD (p = 0.538), and 1 PD (p = 0.077). 11/16 participants had MRS scans with an estimated probability that MRS changes a treatment plan of 0 (0, 0.285).
Conclusion
BZ-SRS with bevacizumab was feasible and well tolerated. There is no significant survival benefit using BZ-SRS with bevacizumab compared to institutional historical controls. Secondary analysis revealed a trend toward improved PFS-6, but not OS-6 after BZ-SRS. MRS scans did not result in changes to SRS treatment plans.
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