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Erschienen in: Child's Nervous System 6/2019

21.03.2019 | Original Article

Bevacizumab-containing regimen in relapsed/progressed brain tumors: a single-institution experience

verfasst von: Amalia Schiavetti, Giulia Varrasso, Maria Giovanna Mollace, Carlo Dominici, Eva Ferrara, Paola Papoff, Claudio Di Biasi

Erschienen in: Child's Nervous System | Ausgabe 6/2019

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Abstract

Aim

The aim of the study is to assess tumor response, treatment-related toxicities, progression-free survival (PFS), and overall survival (OS) in patients with relapsed/refractory brain tumors treated with bevacizumab-containing regimen.

Methods

Patients that had received I and II line treatments with or without megatherapy were included. Doses and schedule were as follows: bevacizumab (BVZ) 10 mg/kg i.v. with irinotecan (IRI) 150 mg/m2 i.v. every 2 weeks ± temozolamide (TMZ) 200 mg/m2 p.o. daily for 5 days every 4 weeks. TMZ was omitted in heavily pretreated cases.

Results

Between 2013 and 2018, 12 patients (3F/9M), median age 161 months (range 66–348), affected with medulloblastoma (n 7), or low-grade glioma (n 2), or high-grade glioma (n 3), received BVZ/IRI association (median courses 20, range 4–67); 3 of them continued single-agent BVZ (median courses 23, range 8–39). TMZ (median courses 8, range 2–26) was administered in eight patients and then stopped in three of them because of myelotoxicity or lack of compliance. Treatment was well tolerated. After 3 months, two complete responses, two partial responses, seven stable diseases, and one progressive disease were observed. Nine cases experienced an improvement in neurological symptoms. Median time to progression was 11 months (95% confidence interval, 4–18 months). Six-month and 2-year PFS were 75% and 42%, respectively. The OS is 33%; interestingly, two cases (one medulloblastoma and one high-grade glioma) are progression-free off-therapy since 30 and 48 months, respectively.

Conclusions

BVZ/IRI association ± TMZ showed encouraging therapeutic activity and low toxicity in this series of relapsed/refractory brain tumors.
Literatur
1.
Zurück zum Zitat Pizzo PA, Poplack DG (2015) Principles and practice of pediatric oncology, 7th edn. Philadelphia Lippincott Williams & Wilkins, Philadelphia, chapters 29A and 29B, pp 628–699 Pizzo PA, Poplack DG (2015) Principles and practice of pediatric oncology, 7th edn. Philadelphia Lippincott Williams & Wilkins, Philadelphia, chapters 29A and 29B, pp 628–699
2.
Zurück zum Zitat Couec ML, André N, Thebaud E et al (2012) Comité Pharmacologie of the SFCE (2012) Bevacizumab and irinotecan in children with recurrent or refractory brain tumors: toxicity and efficacy trends. Pediatr Blood Cancer 59:34–385CrossRefPubMed Couec ML, André N, Thebaud E et al (2012) Comité Pharmacologie of the SFCE (2012) Bevacizumab and irinotecan in children with recurrent or refractory brain tumors: toxicity and efficacy trends. Pediatr Blood Cancer 59:34–385CrossRefPubMed
3.
Zurück zum Zitat Packer RJ, Jakacki R, Horn M, Rood B, Vezina G, MacDonald T, Fisher MJ, Cohen B (2009) Objective response of multiply recurrent low-grade gliomas to bevacizumab and irinotecan. Pediatr Blood Cancer 52:791–795CrossRefPubMed Packer RJ, Jakacki R, Horn M, Rood B, Vezina G, MacDonald T, Fisher MJ, Cohen B (2009) Objective response of multiply recurrent low-grade gliomas to bevacizumab and irinotecan. Pediatr Blood Cancer 52:791–795CrossRefPubMed
4.
Zurück zum Zitat Gururangan S, Fangusaro J, Poussaint TY, McLendon RE, Onar-Thomas A, Wu S, Packer RJ, Banerjee A, Gilbertson RJ, Fahey F, Vajapeyam S, Jakacki R, Gajjar A, Goldman S, Pollack IF, Friedman HS, Boyett JM, Fouladi M, Kun LE (2014) Efficacy of bevacizumab plus irinotecan in children with recurrent low-grade gliomas--a pediatric brain tumor consortium study. Neuro-Oncology 16:310–317CrossRefPubMed Gururangan S, Fangusaro J, Poussaint TY, McLendon RE, Onar-Thomas A, Wu S, Packer RJ, Banerjee A, Gilbertson RJ, Fahey F, Vajapeyam S, Jakacki R, Gajjar A, Goldman S, Pollack IF, Friedman HS, Boyett JM, Fouladi M, Kun LE (2014) Efficacy of bevacizumab plus irinotecan in children with recurrent low-grade gliomas--a pediatric brain tumor consortium study. Neuro-Oncology 16:310–317CrossRefPubMed
5.
Zurück zum Zitat Kalra M, Heath JA, Kellie SJ et al (2015) Confirmation of bevacizumab activity, and maintenance of efficacy in retreatment after subsequent relapse, in pediatric low-grade glioma. J Pediatr Hematol Oncol 37:341–346CrossRef Kalra M, Heath JA, Kellie SJ et al (2015) Confirmation of bevacizumab activity, and maintenance of efficacy in retreatment after subsequent relapse, in pediatric low-grade glioma. J Pediatr Hematol Oncol 37:341–346CrossRef
6.
Zurück zum Zitat Aguilera D, Mazewski C, Fangusaro J, MacDonald TJ, McNall-Knapp RY, Hayes LL, Kim S, Castellino RC (2013) Response to bevacizumab, irinotecan, and temozolomide in children with relapsed medulloblastoma: a multi-institutional experience. Childs Nerv Syst 29:589–596CrossRefPubMedPubMedCentral Aguilera D, Mazewski C, Fangusaro J, MacDonald TJ, McNall-Knapp RY, Hayes LL, Kim S, Castellino RC (2013) Response to bevacizumab, irinotecan, and temozolomide in children with relapsed medulloblastoma: a multi-institutional experience. Childs Nerv Syst 29:589–596CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Parekh C, Jubran R, Erdreich-Epstein A, Panigrahy A, Bluml S, Finlay J, Dhall G (2011) Treatment of children with recurrent high grade gliomas with a bevacizumab containing regimen. J Neuro-Oncol 103:673–680 Erratum in: J Neurooncol 103:681CrossRef Parekh C, Jubran R, Erdreich-Epstein A, Panigrahy A, Bluml S, Finlay J, Dhall G (2011) Treatment of children with recurrent high grade gliomas with a bevacizumab containing regimen. J Neuro-Oncol 103:673–680 Erratum in: J Neurooncol 103:681CrossRef
8.
Zurück zum Zitat Umeda K, Shibata H, Saida S (2015) Long-term efficacy of bevacizumab and irinotecan in recurrent pediatric glioblastoma. Pediatr Int 57:169–1718CrossRefPubMed Umeda K, Shibata H, Saida S (2015) Long-term efficacy of bevacizumab and irinotecan in recurrent pediatric glioblastoma. Pediatr Int 57:169–1718CrossRefPubMed
9.
Zurück zum Zitat Folkman J (1995) Clinical applications of research on angiogenesis. N Engl J Med 333:1757–1763CrossRef Folkman J (1995) Clinical applications of research on angiogenesis. N Engl J Med 333:1757–1763CrossRef
10.
Zurück zum Zitat Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9:669–676CrossRefPubMed Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9:669–676CrossRefPubMed
11.
Zurück zum Zitat Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342CrossRef Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342CrossRef
12.
Zurück zum Zitat Wills B, Cardona AF, Rojas L et al Latin-American Consortium for the Investigation of Lung Cancer (CLICaP)(2017) Survival outcomes according to TIMP1 and EGFR expression in heavily treated patients with advanced non-small cell lung Cancer who received biweekly irinotecan plus bevacizumab. Anticancer Res 37:6429–6436PubMed Wills B, Cardona AF, Rojas L et al Latin-American Consortium for the Investigation of Lung Cancer (CLICaP)(2017) Survival outcomes according to TIMP1 and EGFR expression in heavily treated patients with advanced non-small cell lung Cancer who received biweekly irinotecan plus bevacizumab. Anticancer Res 37:6429–6436PubMed
13.
Zurück zum Zitat Kang TY, Jin T, Elinzano H, Peereboom D (2008) Irinotecan and bevacizumab in progressive primary brain tumors, an evaluation of efficacy and safety. J Neuro-Oncol 89:113–118CrossRef Kang TY, Jin T, Elinzano H, Peereboom D (2008) Irinotecan and bevacizumab in progressive primary brain tumors, an evaluation of efficacy and safety. J Neuro-Oncol 89:113–118CrossRef
14.
Zurück zum Zitat Zhang G, Huang S, Wang Z (2012) A meta-analysis of bevacizumab alone and in combination with irinotecan in the treatment of patients with recurrent glioblastoma multiforme. J Clin Neurosci 19:1636–1640CrossRefPubMed Zhang G, Huang S, Wang Z (2012) A meta-analysis of bevacizumab alone and in combination with irinotecan in the treatment of patients with recurrent glioblastoma multiforme. J Clin Neurosci 19:1636–1640CrossRefPubMed
15.
Zurück zum Zitat Warren KE, Poussaint TY, Vezina G, Hargrave D, Packer RJ, Goldman S, Wen PY, Pollack IF, Zurakowski D, Kun LE, Prados MD, Rutkowski S, Kieran MW (2013) Challenges with defining response to antitumor agents in pediatric neuro-oncology: a report from the response assessment in pediatric neuro-oncology (RAPNO) working group. Pediatr Blood Cancer 60:1397–1401CrossRefPubMedPubMedCentral Warren KE, Poussaint TY, Vezina G, Hargrave D, Packer RJ, Goldman S, Wen PY, Pollack IF, Zurakowski D, Kun LE, Prados MD, Rutkowski S, Kieran MW (2013) Challenges with defining response to antitumor agents in pediatric neuro-oncology: a report from the response assessment in pediatric neuro-oncology (RAPNO) working group. Pediatr Blood Cancer 60:1397–1401CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Friedman HS, Petros WP, Friedman AH, Schaaf LJ, Kerby T, Lawyer J, Parry M, Houghton PJ, Lovell S, Rasheed K, Cloughsey T, Stewart ES, Colvin OM, Provenzale JM, McLendon RE, Bigner DD, Cokgor I, Haglund M, Rich J, Ashley D, Malczyn J, Elfring GL, Miller LL (1999) Irinotecan therapy in adults with recurrent or progressive malignant glioma. J Clin Oncol 17:1516–1525CrossRefPubMed Friedman HS, Petros WP, Friedman AH, Schaaf LJ, Kerby T, Lawyer J, Parry M, Houghton PJ, Lovell S, Rasheed K, Cloughsey T, Stewart ES, Colvin OM, Provenzale JM, McLendon RE, Bigner DD, Cokgor I, Haglund M, Rich J, Ashley D, Malczyn J, Elfring GL, Miller LL (1999) Irinotecan therapy in adults with recurrent or progressive malignant glioma. J Clin Oncol 17:1516–1525CrossRefPubMed
18.
Zurück zum Zitat Bomgaars LR, Bernstein M, Krailo M, Kadota R, Das S, Chen Z, Adamson PC, Blaney SM (2007) Phase II trial of irinotecan in children with refractory solid tumors: a Children’s Oncology Group Study. J Clin Oncol 25:4622–4627CrossRefPubMed Bomgaars LR, Bernstein M, Krailo M, Kadota R, Das S, Chen Z, Adamson PC, Blaney SM (2007) Phase II trial of irinotecan in children with refractory solid tumors: a Children’s Oncology Group Study. J Clin Oncol 25:4622–4627CrossRefPubMed
19.
Zurück zum Zitat Gururangan S, Chi SN, Young Poussaint T, Onar-Thomas A, Gilbertson RJ, Vajapeyam S, Friedman HS, Packer RJ, Rood BN, Boyett JM, Kun LE (2010) Lack of efficacy of bevacizumab plus irinotecan in children with recurrent malignant glioma and diffuse brainstem glioma: a pediatric brain tumor consortium study. J Clin Oncol 28:3069–3075CrossRefPubMedPubMedCentral Gururangan S, Chi SN, Young Poussaint T, Onar-Thomas A, Gilbertson RJ, Vajapeyam S, Friedman HS, Packer RJ, Rood BN, Boyett JM, Kun LE (2010) Lack of efficacy of bevacizumab plus irinotecan in children with recurrent malignant glioma and diffuse brainstem glioma: a pediatric brain tumor consortium study. J Clin Oncol 28:3069–3075CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Mar N, Desjardins A, Vredenburgh JJ (2015) CCR (2015) 20th anniversary commentary: bevacizumab in the treatment of glioblastoma—the progress and the limitations. Clin Cancer Res 21:4248–4250CrossRefPubMed Mar N, Desjardins A, Vredenburgh JJ (2015) CCR (2015) 20th anniversary commentary: bevacizumab in the treatment of glioblastoma—the progress and the limitations. Clin Cancer Res 21:4248–4250CrossRefPubMed
21.
Zurück zum Zitat Bonney PA, Santucci JA, Maurer AJ, Sughrue ME, McNall-Knapp RY, Battiste JD (2016) Dramatic response to temozolomide, irinotecan, and bevacizumab for recurrent medulloblastoma with widespread osseous metastases. J Clin Neurosci 26:161–163CrossRefPubMed Bonney PA, Santucci JA, Maurer AJ, Sughrue ME, McNall-Knapp RY, Battiste JD (2016) Dramatic response to temozolomide, irinotecan, and bevacizumab for recurrent medulloblastoma with widespread osseous metastases. J Clin Neurosci 26:161–163CrossRefPubMed
22.
Zurück zum Zitat Grill J, Massimino M, Bouffet E, Azizi AA, McCowage G, Cañete A, Saran F, le Deley MC, Varlet P, Morgan PS, Jaspan T, Jones C, Giangaspero F, Smith H, Garcia J, Elze MC, Rousseau RF, Abrey L, Hargrave D, Vassal G (2018) Phase II, open-label, randomized, multicenter trial (HERBY) of bevacizumab in pediatric patients with newly diagnosed high-grade glioma. J Clin Oncol 36:951–958CrossRefPubMed Grill J, Massimino M, Bouffet E, Azizi AA, McCowage G, Cañete A, Saran F, le Deley MC, Varlet P, Morgan PS, Jaspan T, Jones C, Giangaspero F, Smith H, Garcia J, Elze MC, Rousseau RF, Abrey L, Hargrave D, Vassal G (2018) Phase II, open-label, randomized, multicenter trial (HERBY) of bevacizumab in pediatric patients with newly diagnosed high-grade glioma. J Clin Oncol 36:951–958CrossRefPubMed
23.
Zurück zum Zitat Fangusaro J, Gururangan S, Poussaint TY et al (2013) Bevacizumab (BVZ)-associated toxicities in children with recurrent central nervous system tumors treated with BVZ and irinotecan (CPT-11): a Pediatric Brain Tumor Consortium Study (PBTC-022). Cancer 119:4180–4187CrossRefPubMed Fangusaro J, Gururangan S, Poussaint TY et al (2013) Bevacizumab (BVZ)-associated toxicities in children with recurrent central nervous system tumors treated with BVZ and irinotecan (CPT-11): a Pediatric Brain Tumor Consortium Study (PBTC-022). Cancer 119:4180–4187CrossRefPubMed
Metadaten
Titel
Bevacizumab-containing regimen in relapsed/progressed brain tumors: a single-institution experience
verfasst von
Amalia Schiavetti
Giulia Varrasso
Maria Giovanna Mollace
Carlo Dominici
Eva Ferrara
Paola Papoff
Claudio Di Biasi
Publikationsdatum
21.03.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Child's Nervous System / Ausgabe 6/2019
Print ISSN: 0256-7040
Elektronische ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-019-04117-z

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