Phase I Trial of Sorafenib in Patients with Recurrent or Progressive Malignant Glioma

Overview

Journal Neuro Oncol

Publisher Oxford University Press

Specialties Neurology
Oncology

Date 2011 Sep 29

PMID 21954442

Citations 22

Authors

L B Nabors

J G Supko

M Rosenfeld

M Chamberlain

S Phuphanich

T Batchelor

S Desideri

X Ye

J Wright

S Gujar

S A Grossman

Affiliations

Soon will be listed here.

Abstract

Sorafenib is an inhibitor of multiple kinases that has demonstrated antiproliferative and antiangiogenic activity in a number of in vitro and in vivo model systems. A phase I study was conducted to determine the maximum tolerated dose (MTD) of sorafenib in patients with recurrent malignant glioma. Sorafenib was given orally, twice a day (BID), continuously in 28-day cycles. The dose was escalated in 2 groups of patients stratified by use of enzyme-inducing antiseizure drugs (± EIASDs). Dose-limiting toxicity (DLT) was defined as any grades 3-4 nonhematological toxicity, grade 4 hematological toxicity, and febrile neutropenia. The number of evaluable patients enrolled in the +EIASD and -EIASD arms were 23 and 24, respectively. DLTs were predominantly dermatological and gastrointestinal effects, as observed in previous clinical trials of sorafenib. The MTD was 600 mg BID for patients receiving EIASDs and 800 mg BID for those who were not. The plasma pharmacokinetics of sorafenib were not significantly affected by the concurrent administration of EIASDs. The MTD of sorafenib given orally BID on a continuous basis was established as 600 mg BID in patients with malignant glioma who were concurrently receiving EIASDs and 800 mg BID in those who were not. Further evaluation is warranted of sorafenib at the recommended MTD against recurrent or progressive malignant glioma in combination with other molecularly targeted drugs or in the newly diagnosed setting concurrent with chemoradiation.

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References

Strumberg D, Clark J, Awada A, Moore M, Richly H, Hendlisz A . Safety, pharmacokinetics, and preliminary antitumor activity of sorafenib: a review of four phase I trials in patients with advanced refractory solid tumors. Oncologist. 2007; 12(4):426-37. DOI: 10.1634/theoncologist.12-4-426. View

Lama G, Mangiola A, Anile C, Sabatino G, De Bonis P, Lauriola L . Activated ERK1/2 expression in glioblastoma multiforme and in peritumor tissue. Int J Oncol. 2007; 30(6):1333-42. View

Gilbert M, Supko J, Batchelor T, Lesser G, Fisher J, Piantadosi S . Phase I clinical and pharmacokinetic study of irinotecan in adults with recurrent malignant glioma. Clin Cancer Res. 2003; 9(8):2940-9. View

Vecht C, Wagner G, Wilms E . Interactions between antiepileptic and chemotherapeutic drugs. Lancet Neurol. 2003; 2(7):404-9. DOI: 10.1016/s1474-4422(03)00435-6. View

Kvale E, Murthy R, Taylor R, Lee J, Nabors L . Distress and quality of life in primary high-grade brain tumor patients. Support Care Cancer. 2009; 17(7):793-9. DOI: 10.1007/s00520-008-0551-9. View

Kane R, Farrell A, Saber H, Tang S, Williams G, Jee J . Sorafenib for the treatment of advanced renal cell carcinoma. Clin Cancer Res. 2006; 12(24):7271-8. DOI: 10.1158/1078-0432.CCR-06-1249. View

Plate K, Breier G, Weich H, Risau W . Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature. 1992; 359(6398):845-8. DOI: 10.1038/359845a0. View

Escudier B, Eisen T, Stadler W, Szczylik C, Oudard S, Siebels M . Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007; 356(2):125-34. DOI: 10.1056/NEJMoa060655. View

Strumberg D, Richly H, Hilger R, Schleucher N, Korfee S, Tewes M . Phase I clinical and pharmacokinetic study of the Novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J Clin Oncol. 2004; 23(5):965-72. DOI: 10.1200/JCO.2005.06.124. View

10.

Wilhelm S, Carter C, Tang L, Wilkie D, McNabola A, Rong H . BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004; 64(19):7099-109. DOI: 10.1158/0008-5472.CAN-04-1443. View

11.

Strumberg D, Voliotis D, Moeller J, Hilger R, Richly H, Kredtke S . Results of phase I pharmacokinetic and pharmacodynamic studies of the Raf kinase inhibitor BAY 43-9006 in patients with solid tumors. Int J Clin Pharmacol Ther. 2002; 40(12):580-1. DOI: 10.5414/cpp40580. View

12.

Mizuta E, Tsubotani A . Preparation of mean drug concentration--time curves in plasma. A study on the frequency distribution of pharmacokinetic parameters. Chem Pharm Bull (Tokyo). 1985; 33(4):1620-32. DOI: 10.1248/cpb.33.1620. View

13.

Clark J, Eder J, Ryan D, Lathia C, Lenz H . Safety and pharmacokinetics of the dual action Raf kinase and vascular endothelial growth factor receptor inhibitor, BAY 43-9006, in patients with advanced, refractory solid tumors. Clin Cancer Res. 2005; 11(15):5472-80. DOI: 10.1158/1078-0432.CCR-04-2658. View

14.

Vredenburgh J, Desjardins A, Herndon 2nd J, Dowell J, Reardon D, Quinn J . Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res. 2007; 13(4):1253-9. DOI: 10.1158/1078-0432.CCR-06-2309. View

15.

Brown P, Jensen A, Felten S, Ballman K, Schaefer P, Jaeckle K . Detrimental effects of tumor progression on cognitive function of patients with high-grade glioma. J Clin Oncol. 2006; 24(34):5427-33. DOI: 10.1200/JCO.2006.08.5605. View

16.

Llovet J, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc J . Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008; 359(4):378-90. DOI: 10.1056/NEJMoa0708857. View

17.

Duran I, Hotte S, Hirte H, Chen E, MacLean M, Turner S . Phase I targeted combination trial of sorafenib and erlotinib in patients with advanced solid tumors. Clin Cancer Res. 2007; 13(16):4849-57. DOI: 10.1158/1078-0432.CCR-07-0382. View

18.

Laack N, Brown P, Ivnik R, Furth A, Ballman K, Hammack J . Cognitive function after radiotherapy for supratentorial low-grade glioma: a North Central Cancer Treatment Group prospective study. Int J Radiat Oncol Biol Phys. 2005; 63(4):1175-83. DOI: 10.1016/j.ijrobp.2005.04.016. View

19.

Strumberg D, Awada A, Hirte H, Clark J, Seeber S, Piccart P . Pooled safety analysis of BAY 43-9006 (sorafenib) monotherapy in patients with advanced solid tumours: Is rash associated with treatment outcome?. Eur J Cancer. 2006; 42(4):548-56. DOI: 10.1016/j.ejca.2005.11.014. View

20.

Moore M, Hirte H, Siu L, Oza A, Hotte S, Petrenciuc O . Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors. Ann Oncol. 2005; 16(10):1688-94. DOI: 10.1093/annonc/mdi310. View