Afinitor for Glioblastoma – pro
There is evidence that the MTOR pathway plays an important role in renal cell cancer. It is also effective in neuroendocine cancer. AFINITOR® is indicated for the treatment of renal cell carcinoma and progressive neuroendocrine tumors of pancreatic origin (PNET) in patients with unresectable, locally advanced or metastatic disease. The safety and effectiveness of AFINITOR® in the treatment of patients with glioblastoma has not been established.
Clinicaltrials.gov cites more than 30 studies of Afinitor in glioblastoma. Preliminary results have not been encouraging. Twenty-two patients with recurrent glioblastoma (GBM) were prospectively treated with everolimus and gefitinib, designed to test the combined inhibition of mammalian target of rapamycin (mTOR) and epidermal growth factor receptor (EGFR) as part of a larger clinical trial. The primary endpoint was radiographic response rate. Secondary endpoints included progression-free survival and correlation of molecular profiles with treatment response. 36% of patients had stable disease and 14% a partial response; however, responses were not durable and only one patient was progression-free at six months. Radiographic changes were not well characterized by conventional response criteria, and implied differential effects of therapy within the tumor and/or antiangiogenic effects. EGFR and PTEN status did not clearly predict response to treatment(1).
On the other hand, a recent PET study(2) showed changed is SUV by PET 2. On August 2012, he US Food and Drug Administration (FDA) approved everolimus tablets for oral suspension (Afinitor Disperz). The drug, a new pediatric dosage form of everolimus (Afinitor), is used to treat patients with subependymal giant cell astrocytoma (SEGA).
1.Teri N. Kreisl, Andrew B. Lassman, Paul S. Mischel, Neal Rosen, Howard I. Scher, Julie Teruya-Feldstein, David Shaffer, Eric Lis and Lauren E. Abrey A pilot study of everolimus and gefitinib in the treatment of recurrent glioblastoma (GBM) Journal of Neuro-Oncology are Volume 92, Number 1, 99-105 2008
2.J. N. Sarkaria, P. J. Peller, E. Galanis, M. S. Jacobson, W. Wu, K. A. Jaeckle, J. C. Buckner; FLT-PET analysis of early response to everolimus in newly diagnosed glioblastoma patients enrolled on NCCTG N057K. J Clin Oncol 29: 2011 (suppl; abstr e12501)
3.L. Yang, M. J. Clarke, B. L. Carlson et al., “PTEN loss does not predict for response to RAD001 (everolimus) in a glioblastoma orthotopic xenograft test panel,” Clinical Cancer Research, vol. 14, no. 12, pp. 39934001, 2008.
4.James Perry, Masahiko Okamoto, Michael Guiou, Katsuyuki Shirai, Allison Errett, and Arnab Chakravarti. Novel Therapies in Glioblastoma. Neurology Research International Volume 2012 (2012
Dasatinib faield studies in glioblastoma in the Radiation Therapy Oncology Group (RTOG) trial 0627
Schiff D, Sarkaria J. Dasatinib in recurrent glioblastoma: failure as a teacher. Neuro Oncol. 2015;17(7):910911. doi:10.1093/neuonc/nov086