A phase i study of temozolomide and everolimus (RAD001) in patients with newly diagnosed and progressive glioblastoma either receiving or not receiving enzyme-inducing anticonvulsants: An NCIC CTG study

Investigational New Drugs

Volumn 30, Issue 6, 2012, Pages 2344-2351

  Mason, Warren P ^a   MacNeil, Mary ^b   Kavan, Petr ^c   Easaw, Jacob ^d   MacDonald, David ^e   Thiessen, Brian ^f   Urva, Shweta ^g   Lwin, Zarnie ^a   McIntosh, Lynn ^h   Eisenhauer, Elizabeth ^h  

^a UNIVERSITY HEALTH NETWORK   (Canada)

^b QUEEN ELIZABETH II HEALTH SCIENCES CENTRE   (Canada)

^c MCGILL UNIVERSITY   (Canada)

^d TOM BAKER CANCER CENTRE   (Canada)

^e London Regional Cancer Centre   (Canada)

^f BRITISH COLUMBIA CANCER AGENCY   (Canada)

^g Novartis Pharmaceuticals Corporation Oncology Business Unit   (United States)

^h Queen's Cancer Research Institute   (Canada)

Author keywords

Chemotherapy; Everolimus; Glioblastoma; Pharmacokinetics; Temozolomide; Toxicities

Indexed keywords

ANTICONVULSIVE AGENT; EVEROLIMUS; TEMOZOLOMIDE;

ADULT; AGED; ANOREXIA; ARTHRALGIA; ARTICLE; CLINICAL ARTICLE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; COUGHING; DIARRHEA; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG ERUPTION; DRUG RESPONSE; EDEMA; EMBOLISM; FATIGUE; FEMALE; GLIOBLASTOMA; HUMAN; LYMPHOCYTE; MALE; MUCOSA INFLAMMATION; NAUSEA; NEUTROPHIL; PHASE 1 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; PRURITUS; RECOMMENDED DRUG DOSE; SIDE EFFECT; THROMBOCYTE; THROMBOSIS; VOMITING;

ADULT; AGED; ANTICONVULSANTS; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BRAIN NEOPLASMS; DACARBAZINE; DRUG COMBINATIONS; FEMALE; GLIOBLASTOMA; HUMANS; IMMUNOSUPPRESSIVE AGENTS; MALE; MIDDLE AGED; PTEN PHOSPHOHYDROLASE; SIROLIMUS; YOUNG ADULT;

EID: 84875530192     PISSN: 01676997     EISSN: 15730646     Source Type: Journal    
DOI: 10.1007/s10637-011-9775-5     Document Type: Article

References (32)

1. Stupp R, Hegi ME, Gilbert MR, Chakravarti A (2007) Chemo-radiotherapy in malignant glioma: standard of care and future directions. J Clin Oncol 25:4127-4136
2. Stupp R, Hegi ME, Mason WP et al (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459-466
3. Ohgaki H, Kleihues P (2007) Genetic pathways to primary and secondary glioblastoma. Am J Pathol 170:1445-1453
4. Louis DN (2006) Molecular pathology of malignant gliomas. Annu Rev Pathol 1:97-117
5. Duerr EM, Rollbrocker B, Hayashi Yet al (1998) PTEN mutations in gliomas and glioneuronal tumors. Oncogene 16:2259-2264
6. Rich JN, Hans C, Jones B et al (2005) Gene expression profiling and genetic markers in glioblastoma survival. Cancer Res 65:4051-4058
7. Smith JS, Tachibana I, Passe SM et al (2001) PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. J Natl Canc Inst 93:1246-1256
8. Chakravarti A, Zhai G, Suzuki Y et al (2004) The prognostic significance of phosphatidylinositol 3-kinase pathway activation in human gliomas. J Clin Oncol 22:1926-1933
9. Cloughesy TF, Yoshimoto K, Nghiemphu P et al (2008) Antitumor activity of rapamycin in a phase I trial for patients with recurrent PTEN-deficient glioblastoma. PLoS Med 5:e8
10. Galanis E, Buckner JC, Maurer MJ et al (2005) Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: a North Central Cancer Treatment Group Study. J Clin Oncol 23:5294-5304
11. Chang SM, Wen P, Cloughesy Tet al (2005) Phase II study of CCI-779 in patients with recurrent glioblastoma multiforme. Investig New Drugs 23:357-361
12. Kreisl TN, Lassman AB, Mischel PS et al (2009) A pilot study of everolimus and gefitinib in the treatment of recurrent glioblastoma (GBM). J Neurooncol 92:99-105
13. Wen PY, Cloughesy T, Kuhn J et al (2009) Phase I/II study of sorafenib and temsirolimus for patients with recurrent glioblastoma (GBM) (NABTC 05-02). J Clin Oncol 27:15S
14. Tanaka K, Sasayama T, Mizukawa K et al (2007) Specific mTOR inhibitor rapamycin enhances cytotoxicity induced by alkylating agent 1-(4-amino-2-methyl- 5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) in human U251 malignant glioma cells. J Neurooncol 84:233-244
15. Motzer RJ, Escudier B, Oudard S et al (2008) Efficacy of ever-olimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372:449-456
16. Dancey J (2010) mTOR signaling and drug development in cancer. Nat Rev Clin Oncol 7:209-219
17. Atkins MB, Yasothan U, Kirkpatrick P (2009) Everolimus. Nat Rev Drug Discov 8:535-536
18. Chan HY, Grossman AB, Bukowski RM (2010) Everolimus in the treatment of renal cell carcinoma and neuroendocrine tumors. Adv Ther 27:495-511
19. O'Donnell A, Faivre S, Burris HA 3rd et al (2008) Phase I phar-macokinetic and pharmacodynamic study of the oral mammalian target of rapamycin inhibitor everolimus in patients with advanced solid tumors. J Clin Oncol 26:1588-1595
20. Sun M, Lughezzani G, Perrotte P, Karakiewicz PI (2010) Treatment of metastatic renal cell carcinoma. Nat Rev Urol 7:327-338
21. Kuhn JG, Chang SM, Wen PY et al (2007) Pharmacokinetic and tumor distribution characteristics of temsirolimus in patients with recurrent malignant glioma. Clin Cancer Res 13:7401-7406
22. Boni J, Leister C, Burns J et al (2007) Pharmacokinetic profile of temsirolimus with concomitant administration of cytochrome p450-inducing medications. J Clin Pharmacol 47:1430-1439
23. Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277-1280
24. Meany HJ, Warren KE, Fox E et al (2009) Pharmacokinetics of temozolomide administered in combination with O6-benzylguanine in children and adolescents with refractory solid tumors. Canc Che-mother Pharmacol 65:137-142
25. Dhodapkar M, Rubin J, Reid JM et al (1997) Phase I trial of temozolomide (NSC 362856) in patients with advanced cancer. Clin Cancer Res 3:1093-1100
26. Newlands ES, Blackledge GR, Slack JA et al (1992) Phase I trial of temozolomide (CCRG 81045: M&B 39831: NSC 362856). Br J Cancer 65:287-291
27. Tabernero J, Rojo F, Calvo E et al (2008) Dose-and schedule-dependent inhibition of the mammalian target of rapamycin pathway with everolimus: a phase I tumor pharmacodynamic study in patients with advanced solid tumors. J Clin Oncol 26:1603-1610
28. Yang L, Clarke MJ, Carlson BL et al (2008) PTEN loss does not predict for response to RAD001 (everolimus) in a glioblastoma orthotopic xenograft test panel. Clin Cancer Res 14:3993-4001
29. Reardon DA, Desjardins A, Vredenburgh JJ et al (2010) Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma. J Neurooncol 96:219-230
30. Gulati N, Karsy M, Albert L et al (2009) Involvement of mTORC1 and mTORC2 in regulation of glioblastoma multiforme growth and motility. Int J Oncol 35:731-740
31. Akhavan D, Cloughesy TF, Mischel PS (2010) mTOR signaling in glioblastoma: lessons learned from bench to bedside. Neuro Oncol 12:882-889
32. Eshleman JS, Carlson BL, Mladek AC et al (2002) Inhibition of the mammalian target of rapamycin sensitizes U87 xenografts to fractionated radiation therapy. Cancer Res 62:7291-7297