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Erschienen in: Cancer Chemotherapy and Pharmacology 4/2017

14.08.2017 | Original Article

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

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

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 4/2017

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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.
Literatur
2.
Zurück zum Zitat Johnson DR, O’Neill BP (2012) Glioblastoma survival in the United States before and during the temozolomide era. J Neurooncol 107:359–364CrossRefPubMed Johnson DR, O’Neill BP (2012) Glioblastoma survival in the United States before and during the temozolomide era. J Neurooncol 107:359–364CrossRefPubMed
3.
Zurück zum Zitat 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 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
4.
Zurück zum Zitat 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 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
5.
Zurück zum Zitat 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 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
6.
Zurück zum Zitat 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 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
7.
Zurück zum Zitat 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 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
8.
Zurück zum Zitat 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 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
9.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
12.
13.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
32.
Zurück zum Zitat Norden AD et al (2008) Bevacizumab for recurrent malignant gliomas: efficacy, toxicity and patters of recurrence. Neurology 70:779–787CrossRefPubMed Norden AD et al (2008) Bevacizumab for recurrent malignant gliomas: efficacy, toxicity and patters of recurrence. Neurology 70:779–787CrossRefPubMed
Metadaten
Titel
Phase II study of bi-weekly temozolomide plus bevacizumab for adult patients with recurrent glioblastoma
verfasst von
Michael A. Badruddoja
Marjorie Pazzi
Abhay Sanan
Kurt Schroeder
Kevin Kuzma
Thomas Norton
Thomas Scully
Daruka Mahadevan
Michael Malek Ahmadi
Publikationsdatum
14.08.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 4/2017
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-017-3405-7

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