With a few exceptions, glioblastoma (GBM) remains largely incurable, and the U.S. Food and Drug Administration (FDA) has approved few treatments for the disease. Surgery (when feasible), radiation, and temozolomide are used in most patients. But even if a newly diagnosed tumor can be surgically excised, recurrences are too common.
In this blog post, I simply list some of the new treatments available in clinical trials for GBM and other high-grade brain tumors. Only drugs that have at least some preliminary results of activity are included, and the list is not meant to be fully comprehensive. The interested reader can judge for herself what might be of interest, keeping in mind that no single treatment is suitable or will work for all GBM patients. Continue reading…
“New research shows that taking molecular variables into account will improve the prognostic classification of the lethal brain cancer called glioblastoma (GBM).
“The study was led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).
“Published in the journal JAMA Oncology, the study found that adding significant molecular biomarkers to the existing GBM classification system improves the prognostic classification of GBM patients who have been treated with radiation and the drug temozolomide.”
“The PD-1 inhibitor nivolumab (Opdivo) was successfully combined with radiotherapy alone or concurrently with temozolomide for patients with newly-diagnosed glioblastoma multiforme (GBM) in cohorts 1c and 1d from the phase I CheckMate-143 study, according to findings presented at the 2016 Society for Neuro-Oncology Annual Meeting.
” ‘The research question was if treatment with nivolumab to block immune checkpoint pathways could potentiate an antitumor immune response and have synergistic effects with radiotherapy or chemoradiotherapy in patients with newly diagnosed GBM,’ stated first author by Antonio Omuro, MD, of the Memorial Sloan Kettering Cancer Center.”
“Treatment with capecitabine and temozolomide (CAPTEM) is an effective therapy for patients with metastatic pancreatic neuroendocrine tumors (pNETs), but the efficacy of several predictive markers previously thought to determine which patients might respond to the regimen could not be validated, according to a presentation at the 2015 NANETS Symposium.
“ ‘In our study we tried to assess the role of potential predictors of response to temozolomide-based regimens in metastatic pNETs,’ according to lead author Mauro Cives, MD, who presented the findings at the 2015 North American Neuroendocrine Tumor Society symposium. The markers the investigators evaluated were expression of MGMT, proliferative activity, and ALT activation.
“Investigators looked at 143 patients with metastatic pNETs treated at Moffitt who had undergone therapy with CAPTEM and retrospectively evaluated them for radiographic response. ‘This is the largest reported cohort of pNET patients treated with temozolomide-based chemotherapy,’ said Cives, a research associate in the Department of GI Oncology at the Moffitt Cancer Center and Research Institute in Tampa, Florida.”
Pancreatic neuroendocrine tumors (PNETs) constitute only about 3% to 5% of all pancreatic cancers. Compared to the most common pancreatic cancer—adenocarcinoma (aka exocrine tumors), PNETs have a longer disease course and better prognosis; the 5-year survival rate is 42% for PNETs, but only about 5% to 6% for adenocarcinomas. When PNETs are localized, they can usually be removed by surgery. However, PNETs tend to metastasize, most often to the liver, and present a formidable treatment challenge at this stage. Continue reading…
The gist: Researchers conducted a clinical trial with volunteer patients to test two drugs, alone and in combination, for recurrent glioblastoma. The two drugs tested were bevacizumab (aka Avastin) and lomustine (aka CeeNU). The researchers found promising results for patients who took both bevacizumab and lomustine, and recommend that further clinical trials be conducted to continue to study the new combination treatment. The patients who participated in the study all had glioblastoma that was treated with temozolomide chemoradiotherapy, but recurred.
“Bevacizumab (Avastin) is frequently used in patients with recurrent glioblastoma, although it is unclear whether responses observed with such treatment result in improved overall survival. In the phase II Dutch BELOB study reported in The Lancet Oncology, Taal et al found that overall survival results supported phase III evaluation of the combination of bevacizumab and lomustine (CeeNU) but not bevacizumab monotherapy…
“In this open-label trial, 153 adult patients from 14 Dutch hospitals with a first recurrence of glioblastoma after temozolomide chemoradiotherapy were randomly assigned between December 2009 and November 2011 to receive oral lomustine at 110 mg/m2 once every 6 weeks, intravenous bevacizumab at 10 mg/kg once every 2 weeks, or combination treatment at the same doses. The primary endpoint outcome was overall survival at 9 months in the intent-to-treat population.
“A preplanned safety analysis after eight patients had received the combination regimen showed that three had grade 3 and two had grade 4 thrombocytopenia, with these toxicities requiring a reduction in bevacizumab dose intensity. The lomustine dose in the combination group was subsequently reduced to 90 mg/m2. In addition to the eight combination recipients getting the higher lomustine dose, 51 received bevacizumab alone, 47 received lomustine alone, and 47 received bevacizumab plus lomustine at 90 mg/m2.
“The investigators concluded, ‘The combination of bevacizumab and lomustine met prespecified criteria for assessment of this treatment in further phase 3 studies. However, the results in the bevacizumab alone group do not justify further studies of this treatment.’ ”
Lian B, Si L, Cui C, Chi Z, et al. Clinical Cancer Research. Jul 5, 2013.
“Mucosal melanoma is rare and associated with extremely poor prognosis. However, standard adjuvant therapy for mucosal melanoma has not been established. We conducted a randomized phase II clinical trial in resected mucosal melanoma (MM) patients to compare the efficacy and safety of high-dose IFN-α2b (HDI) and temozolomide-based chemotherapy as adjuvant therapy.”
Iversen TZ, Brimnes MK, Nikolajsen K, Andersen RS, et al. Oncoimmunology. Feb 1, 2013.
“Therapeutic strategies to deplete lymphocytes, especially regulatory T cells, in cancer patients have been proposed to increase the benefits of (immuno)chemotherapy. In this study, we explored the influence of temozolomide (TMZ) on different T-cell populations and addressed if the depletion of CD4+ T cells would be associated to the clinical benefits of TMZ.”