ABSTRACT
OBJECTIVES: In this study, we analyzed the prognostic value of different MRI progression patterns for survival in patients with recurrent malignant glioma treated with the vascular endothelial growth factor antibody bevacizumab. PATIENTS AND METHODS: Twenty-six adult patients with recurrent malignant glioma treated with bevacizumab or bevacizumab/irinotecan were retrospectively analyzed for the development of contrast-enhanced (T1-weighted MRI) and T2/FLAIR lesions. According to the progression pattern, patients were divided into 3 subgroups: (1) patients with primarily progressive contrast-enhanced lesions in the first MRI after initiation of therapy ('primary PD group'); (2) patients with stable or regressive enhanced lesions but progressive FLAIR lesions ('FLAIR-only PD group'), and (3) patients with stable or regressive contrast-enhanced T1 and FLAIR lesions ('no PD group'). RESULTS: Overall survival (OS) in the 6 patients in the FLAIR-only PD group was not significantly different from the 11 patients in the no PD group (median 311 vs. 254 days, respectively). In contrast, survival in the FLAIR-only PD group was significantly better (p = 0.025) than in the primary PD group. CONCLUSION: FLAIR-only progression is not an independent prognostic factor negatively influencing OS in recurrent glioblastoma treated with bevacizumab and should not lead to discontinuation of bevacizumab therapy.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/drug therapy , Glioblastoma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Adult , Analysis of Variance , Bevacizumab , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Disease Progression , Female , Germany/epidemiology , Glioblastoma/mortality , Glioblastoma/pathology , Humans , Irinotecan , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Prognosis , Retrospective Studies , Survival Analysis , Treatment OutcomeSubject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Melanoma/drug therapy , Melanoma/radiotherapy , Meningeal Neoplasms/drug therapy , Meningeal Neoplasms/radiotherapy , Combined Modality Therapy , Cytarabine/administration & dosage , Dacarbazine/administration & dosage , Dacarbazine/analogs & derivatives , Humans , Injections, Spinal , Liposomes/administration & dosage , Male , Middle Aged , TemozolomideABSTRACT
OBJECTIVE: The NOA-05 multicenter trial was performed to analyze the efficacy of primary chemotherapy with procarbazine and lomustine (PC) in patients with gliomatosis cerebri (GC) and to define clinical, imaging, and molecular factors influencing outcome. METHODS: Thirty-five patients with previously untreated GC were treated with up to six 56-day courses of 110mg/m(2) lomustine on day 1 and 60mg/m(2) procarbazine on days 8 to 21. The primary endpoint was the rate of patients without therapy failure (defined as progressive disease, death from any cause, or termination of PC therapy before the end of course 4) at 8 months after the beginning of PC chemotherapy. RESULTS: The failure-free survival rate at 8 months was 50.3%. Median progression-free survival was 14 months. At progression, 12 patients received salvage radiotherapy. Median overall survival was 30 months. Multivariate analysis revealed isocitrate dehydrogenase 1 (IDH1) gene mutation (hazard ratio [HR], 0.11; 95% confidence interval [CI], 0.02-0.58) and initial presentation without a bilateral symmetrical infiltration pattern on magnetic resonance imaging (HR 0.07, 95%CI 0.01-0.54) as independent prognostic factors associated with prolonged survival. IDH1 mutation was significantly associated with MGMT promoter methylation and an oligodendroglial tumor component. INTERPRETATION: PC chemotherapy is effective in GC. With the NOA-05 trial being the first prospective multicenter trial in GC, PC chemotherapy can be regarded as a promising option for the primary therapy of these tumors.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasms, Neuroepithelial/drug therapy , Adult , Aged , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biomarkers, Tumor/analysis , Brain/pathology , Combined Modality Therapy , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Disease Progression , Disease-Free Survival , Endpoint Determination , Female , Humans , Karnofsky Performance Status , Lomustine/administration & dosage , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasms, Neuroepithelial/pathology , Neoplasms, Neuroepithelial/surgery , Procarbazine/administration & dosage , Prognosis , Prospective Studies , Sample Size , Survival Analysis , Treatment Outcome , Tumor Suppressor Proteins/geneticsABSTRACT
BACKGROUND: Gliomatosis cerebri (GC) is a diffuse infiltrating glial tumor with involvement of at least 3 cerebral lobes. There are only few data on the efficacy of initial chemotherapy in patients with GC. PATIENTS AND METHODS: In 3 neurooncological centers, patients with newly diagnosed GC who had received procarbazine (60 mg/m(2), days 8-21/56) and CCNU (110 mg/m(2), day 1/56) chemotherapy (PC) as initial treatment were analyzed for progression-free survival, overall survival and toxicity. RESULTS: Twelve patients (median age 46 years, range 27-72) were analyzed. The median progression-free survival and the median overall survival were 16 and 37 months. Grade 3 or 4 hematotoxicity was observed in 3 of 12 patients (25%). CONCLUSIONS: These data support the efficacy of PC chemotherapy in newly diagnosed GC. Initial PC chemotherapy should be considered as a treatment option and evaluated in larger clinical trials.
