Cerebrospinal fluid matrix metalloproteinase-9 increases during treatment of recurrent malignant gliomas.

BACKGROUND: Matrix metalloproteinases (MMPs) are enzymes that promote tumor invasion and angiogenesis by enzymatically remodeling the extracellular matrix. MMP-2 and MMP-9 are the most abundant forms of MMPs in malignant gliomas, while a 130 kDa MMP is thought to be MMP-9 complexed to other proteinases. This study determined whether doxycycline can block MMP activity in vitro. We also measured MMP-2 and MMP-9 levels in cerebrospinal fluid (CSF) from patients with recurrent malignant gliomas. METHODS: To determine whether doxycycline can block MMP activity, we measured the extent of doxycyline-mediated MMP-2 and MMP-9 inhibition in vitro using epidermal growth factor receptor (EGFR) transfected U251 glioma cell lines. MMP activity was measured using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) zymography. In addition, patients underwent lumbar puncture for CSF sampling at baseline, after 6 weeks (1 cycle), and after 12 weeks (2 cycles), while being treated with a novel chemotherapy regimen of irinotecan, thalidomide, and doxycycline designed to block growth/proliferation, angiogenesis, and invasion. Irinotecan was given at 125 mg/m2/week for 4 weeks in 6-week cycles, together with continuous doxycycline at 100 mg twice daily on Day 1 and 50 mg twice daily thereafter. Daily thalidomide dose in our cohort was 400 mg. Tumor progression was monitored by magnetic resonance imaging (MRI). RESULTS: Doxycyline in vitro completely abolished MMP-9 activity at 500 mug/ml while there was only 30 to 50% inhibition of MMP-2 activity. Four patients respectively completed 4, 3, 1, and 2 cycles of irinotecan, thalidomide, and doxycycline. Patient enrollment was terminated after one patient developed radiologically defined pulmonary embolism, and another had probable pulmonary embolism. Although CSF MMP-2 and 130 kDa MMP levels were stable, MMP-9 level progressively increased during treatment despite stable MRI. CONCLUSION: Doxycycline can block MMP-2 and MMP-9 activities from glioma cells in vitro. Increased CSF MMP-9 activity could be a biomarker of disease activity in patients with malignant gliomas, before any changes are detectable on MRI.

Optune®: Practical Nursing Applications.

BACKGROUND: After receiving U.S. Food and Drug Administration approval for the treatment of newly diagnosed glioblastoma (GBM) in 2015, following initial approval for treatment of recurrent GBM in 2011, Optune®, a device that uses tumor-treating fields (TTFields) therapy, continues to gain acceptance in the practice environment. OBJECTIVES: This article reviews how TTFields differ from traditional GBM treatment approaches and discusses the pivotal role nurses play in helping patients successfully use this therapy. This includes the importance of adherence to daily continuous therapy because adherence optimizes patient outcomes. METHODS: This article provides oncology nurses with practical guidance to share with patients who are candidates for treatment with TTFields, as well as information to facilitate patients' understanding of the use of Optune and how best to incorporate it into their activities of daily living. FINDINGS: Nurses are key members of the multidisciplinary treatment team that manages patients with GBM. Therefore, oncology nurses are well equipped to educate patients and caregivers about the use of and benefits of adherence to TTFields.

A pilot safety study of lenalidomide and radiotherapy for patients with newly diagnosed glioblastoma multiforme.

PURPOSE: To define the maximum tolerated dose (MTD) of lenalidomide, an analogue of thalidomide with enhanced immunomodulatory and antiangiogenic properties and a more favorable toxicity profile, in patients with newly diagnosed glioblastoma multiforme (GBM) when given concurrently with radiotherapy. PATIENTS AND METHODS: Patients with newly diagnosed GBM received radiotherapy concurrently with lenalidomide given for 3 weeks followed by a 1-week rest period and continued lenalidomide until tumor progression or unacceptable toxicity. Dose escalation occurred in groups of 6. Determination of the MTD was based on toxicities during the first 12 weeks of therapy. The primary endpoint was toxicity. RESULTS: Twenty-three patients were enrolled, of whom 20 were treated and evaluable for both toxicity and tumor response and 2 were evaluable for toxicity only. Common toxicities included venous thromboembolic disease, fatigue, and nausea. Dose-limiting toxicities were eosinophilic pneumonitis and transaminase elevations. The MTD for lenalidomide was determined to be 15 mg/m(2)/d. CONCLUSION: The recommended dose for lenalidomide with radiotherapy is 15 mg/m(2)/d for 3 weeks followed by a 1-week rest period. Venous thromboembolic complications occurred in 4 patients, and prophylactic anticoagulation should be considered.

Immunochemotherapy with rituximab and temozolomide for central nervous system lymphomas.

BACKGROUND: Methotrexate-based and alkylator-based chemotherapy regimens are associated with renal and bone marrow toxicities, which limit their use in patients with central nervous system (CNS) lymphomas. The authors report their experience with an immunochemotherapy regimen consisting of rituximab and temozolomide in patients with primary or metastatic CNS lymphoma. METHODS: Seven patients who had received rituximab and temozolomide were identified from the database of the brain tumor clinic at the authors' institution: three patients had developed recurrent primary CNS lymphoma (PCNSL), one patient had newly diagnosed PCNSL but had poor renal function, and three other patients with systemic non-Hodgkin lymphoma developed recurrent lymphoma in the brain only. Patients were scheduled to receive 4 cycles of induction rituximab on Day 1 and temozolomide on Days 1-5 of a 28-day cycle. Thereafter, their treatment included a total of up to 8 maintenance cycles of temozolomide alone on Days 1-5 of a 28-day cycle. A gadolinium-enhanced magnetic resonance image of the head was obtained after every two cycles of treatment. RESULTS: All patients received rituximab without toxicity. Of the 4 patients who received induction temozolomide at doses > 150 mg/m(2) daily on Days 1-5, 2 experienced Grade 2 leukopenia and thrombocytopenia. Five patients achieved a radiographic complete response, and two patients had partial responses after induction treatment. The median response duration was 6 months (range 3-12+ months), and the median survival was 8 months (range 3+-12+ months). CONCLUSIONS: Although median survival was short, immunochemotherapy with rituximab and temozolomide was well tolerated and exhibited efficacy in this elderly and heavily pretreated cohort. The data obtained in the current study suggest that the optimal induction dose combination consists of rituximab 375 mg/m(2) on Day 1 and temozolomide 150 mg/m(2) daily on Days 1-5.