[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: Bevacizumab (BEV) is widely used in recurrent glioblastoma, alone or in combination with other agents. There
is however no controlled trial to support this use. MATERIAL AND METHODS: In a Dutch multicenter randomized phase II study
patients were assigned to BEV 10 mg/kg day 1, 15 and 29 iv, BEV 10 mg/kg day 1, 15 and 29 iv in combination with 110 mg/m2 lomustine orally on day 1, or lomustine 110 mg/m2 orally on day 1, in a 6- weekly schedule . Eligible were patients with histologically proven glioblastoma, first recurrence
after chemo-irradiation with temozolomide, having concluded radiotherapy more than 3 months ago, with adequate bone marrow,
renal and hepatic function, and WHO performance status (PS) 0-2. Primary endpoint was 9 months overall survival (OS). RESULTS:
Between December 2009 and November 2011, 148 eligible patients were enrolled . Median age was 57 years (range, 24-77) and
median WHO PS was 1. After a preplanned safety review after the first 8 patients the lomustine dose in the combination arm
was reduced to 90 mg/m2, 44 patients were treated at this dose level. 130 patients were evaluable for response. Nine month
OS [95% confidence interval] was 43% [29, 57] in the lomustine arm, 38% [25, 51] in the BEV arm, and 59% [43, 72] in the BEV/lomustine
90 arm. Objective response rate (complete or partial response) by local investigator was 5% in the lomustine arm, 38% in the
BEV arm and 34% in the BEV/lomustine 90 arm. CONCLUSION: The combination bevacizumab/lomustine warrants further investigation,
and is currently investigated in the randomized controlled phase III EORTC trial 26101. At the meeting the analysis based
on IDH and MGMT status and the first results on the radiology review, pattern of progression and clinical impact of isolated
T2/FLAIR progression will be presented.
[Show abstract][Hide abstract] ABSTRACT: Everolimus has important clinical activity in various malignancies, but its use can be complicated by respiratory adverse events. Important everolimus-induced respiratory adverse events are interstitial lung disease (ILD) and infections, either typical or opportunistic. Furthermore, non-everolimus-related respiratory events can occur. Due to the non-specific presentation of most of these respiratory disorders, it is often not possible to differentiate between these causes on clinical and radiological grounds only. Considering the potential fatal nature of opportunistic infections, these are especially important to recognize. To be able to distinguish between ILD and (opportunistic) infections as the underlying cause, an aggressive diagnostic workup, including bronchoalveolar lavage, should be performed in patients treated with everolimus who develop respiratory disease. We report three cases of severe opportunistic pulmonary infections during everolimus treatment, concerning two Pneumocystis jirovecii pneumonia infections. These cases illustrate the diagnostic challenges of respiratory adverse events and the importance of a thorough diagnostic workup for correct diagnosis and treatment.
No preview · Article · Mar 2014 · Targeted Oncology
[Show abstract][Hide abstract] ABSTRACT: Primary intracranial germ-cell tumors are rare tumors primarily of adolescence, and literature on this disease in adults is scarce. The available evidence on intracranial germ-cell tumors is reviewed with a focus on adult patients whenever possible, and used to make suggestions for diagnosis and treatment. Diagnostic and treatment algorithms were developed to provide an evidence-based backbone to base treatment on in adult patients with a (suspected) primary intracranial germ-cell tumor.
Full-text · Article · Mar 2013 · Journal of Neuro-Oncology
[Show abstract][Hide abstract] ABSTRACT: Medulloblastoma is a rare tumor in adults. There is no standard treatment, and extrapolation of treatment results from the pediatric population is flawed by differences in behavior of the tumor and in tolerance of treatment at different ages. In this case report, a patient with medulloblastoma and leptomeningeal metastases after standard chemoradiotherapy had rapid progressive disease after second-line temozolomide. However, partial response was achieved with third-line etoposide and carboplatin. Treatment choice should be based on toxicity management and the patient’s history to obtain higher efficacy, as in our case.
[Show abstract][Hide abstract] ABSTRACT: High-grade glioma patients receiving concomitant chemoradiotherapy with temozolomide 75mg/m(2) during six to seven weeks or dose-dense temozolomide regimens especially in combination with chronic use of corticosteroids have a high risk for developing Pneumocystis jirovecii pneumonia. In this review, we define risk groups and propose a guideline for prophylaxis using risk stratification.
No preview · Article · Aug 2012 · Critical reviews in oncology/hematology
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: Glioblastoma multiforme is the most common and aggressive primary brain tumor. Valproate has been used as an anti-epileptic drug and mood stabilizer for decades. Recently, it was found to inhibit the proliferation of various cancers including glioblastoma multiforme.
AREAS COVERED: We provide a comprehensive review of the mechanisms of action of valproate in gliomas, of its potential side effects and of the published clinical results obtained with this drug in glioblastomas. Valproate inhibits a subset of histone deacetylases and cellular kinases, and affects gene transcription through histone hyperacetylation, DNA hypomethylation and the modulation of several transcription factors. As a result, VPA induces differentiation of glioma cells, can prevent their invasion in surrounding tissues and may inhibit tumor angiogenesis. VPA can also inhibit DNA repair, thereby potentiating cytotoxic treatments such as chemotherapies or radiation therapy. Based on these mechanisms and case reports of glioblastoma remissions following VPA treatment, several clinical studies currently assess the therapeutic potential of VPA in glioma therapy.
EXPERT OPINION: The combination of VPA treatment with chemotherapy and radiotherapy in glioblastoma appears a rational option that deserves well-designed prospective clinical trials that assess the efficacy and the molecular characteristics of the responding tumors in these patients.
No preview · Article · Jun 2012 · Expert Opinion on Investigational Drugs