Thalidomide as Palliative Treatment in Patients with Advanced Secondary Glioblastoma

Abstract

Background: For its numerous abilities including sedation, we have been using thalidomide (TH) as the ‘last therapeutic option' in patients with advanced gliomas. We noticed that a small subgroup, i.e. patients with secondary glioblastoma (GBM, whose GBM has evolved over several months or years from a less malignant glioma), survived for prolonged periods. Therefore, we retrospectively evaluated the outcomes of patients with secondary GBM treated with TH at our centre. Patients and Methods: Starting in the year 2000, we have studied 23 patients (13 females, 10 males, with a median age of 31.5 years) with secondary GBM who have received palliative treatment with TH 100 mg at bedtime. All patients had previously undergone radiotherapy and received at least 1 and up to 5 regimens of chemotherapy. Results: The median duration of TH administration was 4.0 months (range 0.8-32). The median duration of overall survival after the start of TH therapy was 18.3 months (range 0.8-57). Eleven patients with secondary GBM survived longer than 1 year. Symptomatic improvement was most prominent in the restoration of a normal sleep pattern. Conclusion: The palliative effects of TH, especially the normalization of a sleep pattern, were highly valued by patients and families. The prolongation of survival of patients with secondary GBM has not been reported previously. © 2014 S. Karger AG, Basel

Receptor tyrosine kinase targeting in glioblastoma: performance, limitations and future approaches

“…Among them, afatinib and dacomitinib were approved by the FDA. In 2015, a phase I/phase II study regarding afa- Imatinib showed no significant changes in the HGGs and especially GBM tumor growth [46] Better results were obtained in combination with hydroxyurea [47] Tandutinib had little effect [ Vatalanib enhances the antiangiogenic activity [54] Disappointing results were obtained for pazopanib in combination with lapatinib [57] No promising activity for GBM patients treated with sunitinib [58] Cediranib is an inhibitor of VEGFR, PDGFR, and c-kit [59] Thalidomide had a good effect as palliative drug in advanced secondary glioblastoma [60] Cabozantinib had good results both in vitro and in clinical trials [61,62] SU1498 had a limited anti-tumor activity [51] EGFR -epidermal growth factor receptor, PDGFR -platelet-derived growth factor receptor, IGF-R -insulin-like growth factor receptor, VEGFR -vascular endothelial growth factor receptor, FDA -Food and Drug Administration, ERK -extracellular signal-regulated kinases, HGGs -high-grade gliomas, GBs -glioblastomas, c-kittransmembrane tyrosine kinase receptor tinib alone or in combination with temozolomide proved that the drug was safe but with limited activity [37]. Also, single-agent dacomitinib proved to have limited activity in a phase II clinical trial in recurrent glioblastoma patients with EGFR amplification [38], following preclinical studies with good results [39].…”

“…Another antiangiogenic agent which proved good effects on GB patients is thalidomide. The drug had a good effect when used as a palliative drug for patients with advanced secondary GB [60]. SU1498 is a VEGFR inhibitor that proved to have a cytotoxic effect on GB9B cells.…”

A systematic review of ongoing clinical trials in optic pathway gliomas

“…The mechanism of anti-angiogenic action is not fully known [40]. Its use has been investigated in the care of high-grade glioma [41].…”

Challenging the indiscriminate use of temozolomide in pediatric high‐grade gliomas: A review of past, current, and emerging therapies

“…While their mechanism of action is not entirely elucidated, they seem to exert their immunomodulatory and antiangiogenic properties via inhibition of TNF, interleukin–6, IgG, and VEGF; costimulation of T cells and NK cells; and increased interferon–gamma and interleukin–2 . Thalidomide has been tested in adults with newly diagnosed and relapsed glioblastoma . Additionally, pomalidomide has been evaluated in a phase II trial for children with relapsed/refractory brain tumors (NCT03257631), and although it did not show clinically meaningful antitumor efficacy as single agent, sustained responses in children with HGG have been reported …”

“…[82][83][84] Thalidomide has been tested in adults with newly diagnosed and relapsed glioblastoma. [85][86][87] Additionally, pomalidomide has been evaluated in a phase II trial for children with relapsed/refractory brain tumors (NCT03257631), and although it did not show clinically meaningful antitumor efficacy as single agent, sustained responses in children with HGG have been reported. 88…”