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14-08-2017 | Glioblastoma multiforme | Article

Phase II study of bi-weekly temozolomide plus bevacizumab for adult patients with recurrent glioblastoma

Journal: Cancer Chemotherapy and Pharmacology

Authors: Michael A. Badruddoja, Marjorie Pazzi, Abhay Sanan, Kurt Schroeder, Kevin Kuzma, Thomas Norton, Thomas Scully, Daruka Mahadevan, Michael Malek Ahmadi

Publisher: Springer Berlin Heidelberg

Abstract

Purpose

Bevacizumab is an active anti-angiogenic agent in the treatment of recurrent glioblastoma. Temozolomide can prolong survival in patients with newly diagnosed glioblastoma. At recurrence, alternate dosing of temozolomide has shown to further deplete methyl-guanine-methyltransferase (MGMT) conferring added activity for patients who have progressed on the standard dosing regimen. In this study, bevacizumab plus biweekly temozolomide was evaluated for efficacy in adult patients with recurrent glioblastoma.

Methods

Thirty patients with recurrent glioblastoma were treated with bevacizumab on (10 mg/kg i.v.) days 1 and 15 of a 28-day cycle combined with temozolomide (100 mg/m²) on days 1–5 and 15–19 on a 28-day cycle. Responses were assessed at week 4 and then every 8 weeks. MGMT status and quality of life measures were also assessed.

Results

Overall response rate from diagnosis was 51 weeks, the 6-month progression-free survival was 52%, and median time to tumor progression was 5.5 months.

Conclusion

Bevacizumab plus bi-weekly temozolomide was well tolerated and may be a salvage regimen to be considered in a subset of patients with recurrent glioblastoma.

CBTRUS (Central Brain Tumor Registry of the United States) (2015) http://www.cbtrus.org. Accessed 1 April 2015

Johnson DR, O’Neill BP (2012) Glioblastoma survival in the United States before and during the temozolomide era. J Neurooncol 107:359–364CrossRefPubMed

Stupp R, Dietrich PY, Kraljevic SO, Pica A, Maillard I, Maeder P et al (2002) Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol 20:1375–1382CrossRefPubMed

Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE et al (2009) Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 27:4733–4740CrossRefPubMed

Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I et al (2009) Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 27:740–745CrossRefPubMed

Wen PY. Phase II study of prolonged daily temozolomide for low-grade glioma. In Schering-Plough oncology North America Temodar investigator advisory board. 2007. St. Petersburg, FL

Perry JR, Bélanger K, Mason WP, Fulton D, Kavan P, Easaw J et al (2010) Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE Study. J Clin Oncol 28:2051–2057CrossRefPubMed

Gilbert MR, Wang M, Aldape KD, Stupp R, Hegi ME, Jaeckle KA et al (2013) Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. J Clin Oncol 31:4085–4091CrossRefPubMedPubMedCentral

Verhoeff JJC, Lavini C, van Linde ME, Stalpers LJA, Majoie CBLM, Reijneveld JC et al (2010) Bevacizumab and dose-intense temozolomide in recurrent high-grade glioma. Ann Oncol 21:1723–1727CrossRefPubMed

10.

Desjardins A, Reardon DA, Coan A, Marcello J, Herndon JE, Bailey L et al (2012) Bevacizumab and daily temozolomide for recurrent glioblastoma. Cancer 118:1302–1312CrossRefPubMed

11.

Onco Methylome Sciences, Durham, NC

12.

Castle Biosciences, Friendswood, TX

13.

Vlassenbroeck I, Califice S, Diserens AC, Migliavacca E, Straub J, di Stefano I et al (2008) Validation of real-time methylation-specific PCR to determine O⁶-methylguanine-DNA methyltransferase gene promoter methylation in glioma. J Med Diagn 10:332–337

14.

Colman H, Zhang L, Sulman EP, McDonald JM, Shooshtari NL, Rivera A et al (2010) A multigene predictor of outcome in glioblastoma. Neuro Oncol 12(1):49–57CrossRefPubMed

15.

Vredenburgh JJ, Desjardins A, Herndon JE 2nd, Marcello J, Reardon DA, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Sampson J, Wagner M, Bailey L, Bigner DD, Friedman AH, Friedman HS (2007) Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 25(30):4722–4729CrossRefPubMed

16.

Stupp R, Hegi ME, Mason WP, Vandenbent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups, National Cancer Institute of Canada Clinical Trials Group (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(5):459–466CrossRefPubMed

17.

Tolcher AW, Gerson SL, Denis L, Geyer C, Hammond LA, Patnaik A et al (2003) Marked inactivation of O⁶-alkylguanine-DNA alkyltransferase activity with protracted temozolomide schedules. Br J Cancer 88:1004–1011CrossRefPubMedPubMedCentral

18.

Kesari S, Schiff D, Drappatz J, LaFrankie D, Doherty L, Macklin EA et al (2009) Phase II study of protracted daily temozolomide for low-grade gliomas in adults. Clin Cancer Res 15:330–337CrossRefPubMed

19.

Balmaceda C, Peereboom D, Pannullo S, Cheung YKK, Fisher PG, Alavi J et al (2008) Multi-institutional phase II study of temozolomide administered twice daily in the treatment of recurrent high-grade gliomas. Cancer 112:1139–1146CrossRefPubMed

20.

Brandes AA, Tosoni A, Cavallo G, Bertorelle R, Gioia V, Franceschi E et al (2006) Temozolomide 3 weeks on and 1 week off as first-line therapy for recurrent glioblastoma: phase II study from gruppo italiano cooperativo di neuro-oncologia (GICNO). Br J Cancer 95:1155–1160CrossRefPubMedPubMedCentral

21.

Jauch T, Hau P, Bogdahn U (2007) Re-challenge with temozolomide (TMZ) at recurrence in high-grade gliomas (HGG) [abstract 2034]. J Clin Oncol 25(suppl):83s

22.

Wick A, Felsberg J, Steinbach JP, Herrlinger U, Platten M, Blaschke B et al (2007) Efficacy and tolerability of temozolomide in an alternating weekly regimen in patients with recurrent glioma. J Clin Oncol 25:3357–3361CrossRefPubMed

23.

Wick W, Steinbach JP, Küker WM, Dichgans J, Bamberg M, Weller M (2004) One week on/one week off: a novel active regimen of temozolomide for recurrent glioblastoma. Neurology 62:2113–2115CrossRefPubMed

24.

Galanis E, Anderson SK, Lafky JM, Uhm JH, Giannini C, Kumar SK, Kimlinger TK, Northfelt DW, Flynn PJ, Jaeckle KA, Kaufmann TJ, Buckner JC (2013) Phase II study of bevacizumab in combination with sorafenib in recurrent glioblastoma (N0776): a north central cancer treatment group trial. Clin Cancer Res 19(17):4816–4823. doi:10.1158/1078-0432.CCR-13-0708 (Epub 2013 Jul) CrossRefPubMed

25.

Sathornsumetee S, Desjardins A, Vredenburgh JJ, McLendon RE, Marcello J, Herndon JE, Mathe A, Hamilton M, Rich JN, Norfleet JA, Gururangan S, Friedman HS, Reardon DA (2010) Phase II trial of bevacizumab and erlotinib in patients with recurrent malignant glioma. Neuro Oncol 12(12):1300–1310CrossRefPubMedPubMedCentral

26.

Soffietti R, Trevisan E, Bertero L, Cassoni P, Morra I, Fabrini MG, Pasqualetti F, Lolli I, Castiglione A, Ciccone G, Rudà R (2014) Bevacizumab and fotemustine for recurrent glioblastoma: a phase II study of AINO (Italian Association of Neuro-Oncology). J Neurooncol 116(3):533–541CrossRefPubMed

27.

Reardon DA, Desjardin A, Peters KB, Gururangan S, Sampson JH, McLendon RE, Herndon JE, Bulusu A, Threatt S, Friedman AH, Vredenburgh JJ, Friedman HS (2012) Phase II study of carboplatin, irinotecan, and bevacizumab for bevacizumab naïve, recurrent glioblastoma. J Neuro Oncol 107(1):155–164CrossRef

28.

Lassen U, Sorensen M, Gaziel TB, Hasselbalch B, Poulsen HS (2013) Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme. Anticancer Res 33(4):1657–1660PubMed

29.

Reardon DA, Desjardins A, Vredenburgh JJ, Gururangan S, Sampson JH, Sathornsumetee S, McLendon RE, Herndon JE 2nd, Marcello JE, Norfleet J, Friedman AH, Bigner DD, Friedman HS (2009) Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study. Br J Cancer 101(12):1986–1994CrossRefPubMedPubMedCentral

30.

Reardon DA, Desjardins A, Peters KB, Vredenburgh JJ, Gururangan S, Sampson JH, McLendon RE, Herndon JE, Coan A, Threatt S, Friedman AH, Friedman HS (2011) Phase II study of carboplatin, irinotecan and bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy. Cancer 117(23):5351–5358CrossRefPubMedPubMedCentral

31.

Iwamoto FM et al (2009) Pattterns of relapse and prognosis after bevacizumab failure in recurrent gliobmastoma. Neurology 73:1200–1206CrossRefPubMedPubMedCentral

32.

Norden AD et al (2008) Bevacizumab for recurrent malignant gliomas: efficacy, toxicity and patters of recurrence. Neurology 70:779–787CrossRefPubMed