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.
Antiangiogenic drugs have emerged as effective treatment options for patients with recurrent malignant gliomas (MGs). Though this class of drugs is generally well tolerated, rare life-threatening ...complications, including thromboembolism, hemorrhage, and gastrointestinal (GI) perforation, are reported. We describe six cases of GI perforation among 244 glioma patients (2.5%) during treatment with antiangiogenic agents in combination with chemotherapy and corticosteroids. Two patients succumbed to this complication, and the others recovered. Because GI perforation is a life-threatening yet treatable complication, neurooncologists must have a low threshold to consider it in patients on antiangiogenic drug therapy who present with abdominal pain and other GI complaints.
Medical Care of Patients With Brain Tumors Drappatz, Jan
Continuum (Minneapolis, Minn.),
2012-April, 2012-Apr, 2012-04-00, 20120401, Letnik:
18, Številka:
2, Neuro-oncology
Journal Article
PURPOSE OF REVIEW:Patients with brain tumors require close attention to medical issues resulting from their disease or its therapy. Effective medical management results in decreased morbidity and ...mortality and improved quality of life. The most frequent neurology-related issues that arise in these patients include seizures, peritumoral edema, venous thromboembolism, fatigue, and cognitive dysfunction. This article focuses on the most recent findings for the management of the most relevant medical complications among patients with brain tumors.
RECENT FINDINGS:Increasing evidence suggests that anticoagulation in patients with thromboembolic complications is safe even when they are receiving antiangiogenic therapy. There are also increasing data to support the use of newer, non–enzyme-inducing antiepileptic drugs, which have the advantage of lacking interactions with antineoplastic agents and are as effective as their older counterparts at preventing seizures. Relatively few studies have addressed the management of fatigue and depression, and definitive recommendations cannot be made.
SUMMARY:Corticosteroids to treat vasogenic edema should be used at the minimum amount required to control symptoms and should be tapered as quickly as possible. Anticonvulsants should be used only if patients have had seizures. Non–enzyme-inducing antiepileptic drugs are preferred to minimize interactions with concurrently administered chemotherapy. Thromboembolic complications are common and are preferably treated with low-molecular-weight heparins. Only patients with hemorrhagic complications require an inferior vena cava filter. Cognitive deficits are frequent in patients with brain tumors and include problems such as poor short-term memory, distractibility, personality change, emotional lability, loss of executive function, and decreased psychomotor speed. Stimulants can help to improve these symptoms.
GRN1005 is a peptide-drug conjugate with the ability to penetrate the blood-brain barrier (BBB) and tumor cells by targeting the low-density lipoprotein receptor-related protein-1. We conducted a ...first-in-human phase I trial of GRN1005 in patients with recurrent glioma.
Patients received GRN1005 by intravenous infusion every 3 weeks. Doses were escalated using a modified Fibonacci scheme. Study objectives included safety, tolerability, identification of the maximum tolerated dose (MTD), pharmacokinetics, and preliminary evidence of efficacy. Tumor extracted from patients undergoing surgery following administration of GRN1005 was analyzed to determine whether therapeutic concentrations of GRN1005 were achieved.
Sixty-three patients received GRN1005 at doses of 30 to 700 mg/m(2) every 3 weeks. Therapy was well tolerated with neutropenia, leucopenia, and fatigue as the most frequent drug-associated grade 3/4 or higher toxicities. The MTD was 650 mg/m(2) every 3 weeks. Dose-limiting toxicities were grade 3 mucositis and grade 4 neutropenia. There was no evidence of central nervous system toxicity or antibody production. Pharmacokinetic analysis showed that exposure to GRN1005 was dose proportional. We observed one complete and two partial responses. Eight of 27 patients dosed ≥ 420 mg/m(2) had stable disease, which lasted a median of 51 days. Therapeutic concentrations of GRN1005 and free paclitaxel were shown in tumor tissue of surgical patients dosed with ≥ 200 mg/m(2).
GRN1005 delivers paclitaxel across the BBB and achieves therapeutic concentrations in tumor tissue. It has similar toxicity to paclitaxel and appears to have activity in recurrent glioma. The recommended phase II dose is 650 mg/m(2) every 3 weeks.
Medical therapies for meningiomas Wen, Patrick Y.; Quant, Eudocia; Drappatz, Jan ...
Journal of neuro-oncology,
09/2010, Letnik:
99, Številka:
3
Journal Article
Recenzirano
Meningiomas are the most common primary brain tumor in adults. Although the majority of these tumors can be effectively treated with surgery and radiation therapy, an important subset of patients ...have inoperable tumors, or develop recurrent disease after surgery and radiotherapy, and require some form of medical therapy. There are increasing numbers of studies evaluating various medical therapies but the results remain disappointing. Chemotherapies and hormonal therapies have been generally ineffective, although somatostatin analogues may have therapeutic potential. There is also increasing interest in targeted molecular therapies. Agents inhibiting platelet derived growth factor receptors and epidermal growth factor receptors have shown little efficacy, but molecular agents inhibiting vascular endothelial growth factor receptors appear to have some promise. As with other tumors, advances in the medical therapies for meningiomas will require improved understanding of the molecular pathogenesis of these tumors, more predictive preclinical models, and efficient mechanisms for conducting clinical trials, given the small population of eligible patients.
Atypical and anaplastic (WHO Grades II and III) meningiomas are aggressive tumors, and patients often progress despite surgery and radiation. There is no known effective chemotherapeutic option for ...these patients. Meningiomas have a high expression of vascular endothelial growth factor receptor (VEGFR). We sought to retrospectively study the activity of bevacizumab, which is an anti-angiogenic agent targeting the VEGF pathway in these tumors. This is a retrospective review of WHO Grade II and III meningiomas treated at four institutions, selecting only those patients who received bevacizumab. We analyzed radiographic response according to standard RANO criteria, progression-free survival (PFS) and overall survival from the initiation of bevacizumab therapy using Kaplan–Meier statistics. We identified 15 patients across four institutions who carried a diagnosis of atypical or anaplastic meningioma and were treated with bevacizumab. Best radiographic response was stable disease. MR perfusion studies showed decreased tumor blood volume in one patient. Three patients developed non-fatal intratumoral hemorrhage. Median PFS was 26 weeks (95 % CI, 10–29 weeks). Six month PFS rate was 43.8 % (95 % CI, 15.7–69.1 %). Bevacizumab was well-tolerated in our patients, and may be considered in patients who have exhausted radiation and surgical options. Prospective studies are required to define the safety and efficacy of bevacizumab in atypical and anaplastic meningiomas.
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