Exp Clin Endocrinol Diabetes 2021; 129(03): 178-185
DOI: 10.1055/a-1260-3975
Article

Bevacizumab in Aggressive Pituitary Adenomas – Experience with 3 Patients

Katharina Osterhage
1   Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
Roman Rotermund
1   Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
Michael Droste
2   Endocrinology Medicover MVZ, Oldenburg, Germany
,
Judith Dierlamm
3   Department of Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
Wolfgang Saeger
4   Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
Stephan Petersenn
5   ENDOC Center for Endocrine Tumors, Hamburg, Germany
,
Jens Aberle
6   Department of Endocrinology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
Jörg Flitsch
1   Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
› Author Affiliations

Abstract

Objective To investigate bevacizumab as alternative treatment of aggressive pituitary adenomas after exhaustion of standard therapies.

Design and Methods Retrospectively, 3 patients undergoing microscopic transsphenoidal surgery of aggressive pituitary adenomas from 2008 till 2018 that were treated with bevacizumab were identified. Development of disease and treatment were evaluated.

Results Two patients suffered from ACTH-secreting adenomas, one from a non-functioning adenoma. All patients underwent multiple surgical, chemo- and radiotherapeutical approaches including temozolomide, showing favorable results in one patient. Deterioration of clinical condition in all patients led to an individual, palliative attempt of bevacizumab. Patients 1 and 2 showed a decrease of ACTH after first administrations, but therapy had to be ended shortly after due to a further deterioration of their condition. Patient 3 showed a stabilization of the disease for 18 months. Patients died 8, 15 and 7 years after initial diagnosis, respectively, and 2, 4, and 24 months after initiation of bevacizumab therapy, respectively.

Conclusion The demonstrated results suggest a considerable effect of bevacizumab in aggressive pituitary adenomas. The advanced stage of disease in all three patients, the overall short period of administration and just one patient showing a clinical benefit do not allow a general statement on the effectiveness. At the current stage of clinical experience, an approach with bevacizumab can be considered as an individual palliative attempt of treatment, when standard treatments are exhausted. Our results underline the need for further studies to evaluate this drug as potential player in therapy resistant aggressive pituitary tumors.



Publication History

Received: 29 April 2020
Received: 15 July 2020

Accepted: 06 August 2020

Article published online:
07 December 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Osamura RY, Lopes MBS, Grossman A. et al. World Health Organization Classification of Tumours of Endocrine Organs. 4th edn.. IARC, Lyon; p13
  • 2 Chesney K, Memel Z, Pangal DJ. et al. Variability and lack of prognostic value associated with atypical pituitary adenoma diagnosis: A systematic review and critical assessment of the diagnostic criteria. Neurosurgery 2018; 83: 602-610
  • 3 Saeger W, Lüdecke DK, Buchfelder M. et al. Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry. Eur J Endocrinol 2007; 156: 203-216
  • 4 Saeger W. German Pituitary Tumors Registry. https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=DE&Expert=220637
  • 5 Wong A, Eloy J, Liu J. The Role of Bilateral Adrenalectomy in the Treatment of Refractory Cushing's Disease. Neurosurg Focus 2015; 38: E9
  • 6 Fadul CE, Kominsky AL, Meyer LP. et al. Long-term response of pituitary carcinoma to temozolomide. Report of two cases. Journal of Neurosurgery 2006; 105: 621-626
  • 7 Lim S, Shahinian H, Maya MM. et al. Temozolomide: A novel treatment for pituitary carcinoma. Lancet Oncology 2006; 7: 518-520
  • 8 Syro LV, Uribe H, Penagos LC. et al. Antitumour effects of temozolomide in a man with a large, invasive prolactin-producing pituitary neoplasm. Clinical Endocrinology 2006; 65: 552-553
  • 9 Raverot G, Burman P, McCormack AI. et al. European Society of Endocrinology clinical practice guidelines for the management of aggressive pituitary tumours and carcinomas. Eur Endocrinol 2017; 178: G1-G24
  • 10 McCormack A, Dekkers OM, Petersenn S. et al. Treatment of aggressive pituitary tumours and carcinomas: Results of A European Society of Endocrinology (ESE) survey 2016. Eur J Endocrinol 2018; 178: 265-276
  • 11 Bengtsson D, Schrøder HD, Andersen M. et al. Long-term outcome and MGMT as a predictive marker in 24 patients with atypical pituitaryadenomas and pituitary carcinomas given treatment with temozolomide. J Clin Endocrinol Metab 2015; 100: 1689-1698
  • 12 Ortiz LD, Syro LV, Scheithauer BW. et al. Anti-VEGF therapy in pituitary carcinoma. Pituitary. 2012; 15: 445-449
  • 13 Touma W, Hoostal S, Peterson RA. et al. Successful treatment of pituitary carcinoma with concurrent radiation, temozolomide, and bevacizumab after resection. J Clin Neurosci 2017; 41: 75-77
  • 14 Rutkowski MJ, Alward RM, Chen R. et al. Atypical pituitary adenoma: A clinicopathologic case series. J Neurosurg 2018; 128: 1058-1065
  • 15 Del Basso De Caro M, Solari D. et al. Atypical pituitary adenomas: clinical characteristics and role of ki-67 and p53 in prognostic and therapeutic evaluation. A series of 50 patients. Colao Neurosurg Rev 2017; 40: 105-114
  • 16 Lv L, Hu Y, Yin S. et al. Clinically aggressive phenotype: A clinicopathological case series of atypical pituitary adenomas. Clin Neurol Neurosurg 2018; 167: 93-98
  • 17 Lelotte J, Mourin A, Fomekong E. et al. Both invasiveness and proliferation criteria predict recurrence of non-functioning pituitarymacroadenomas after surgery: A retrospective analysis of a monocentric cohort of 120 patients. Eur J Endocrinol 2018; 178: 237-246
  • 18 Zaidi HA, Cote DJ, Dunn IF. et al. Predictors of aggressive clinical phenotype among immunohistochemically confirmed atypicaladenomas. J Clin Neurosci 2016; 34: 246-251
  • 19 Maclean J, Aldridge M, Bomanji J. et al. Peptide receptor radionuclide therapy for aggressive atypical pituitary adenoma/carcinoma: Variable clinical response in preliminary evaluation. Pituitary. 2014; 17: 530-538
  • 20 Waligórska-Stachura J, Gut P, Sawicka-Gutaj N. et al. Growth hormone-secreting macroadenoma of the pituitary gland successfully treated with the radiolabeled somatostatin analog (90)Y-DOTATATE: Case report. J Neurosurg 2016; 125: 346-349
  • 21 Rotman L, Brooks Vaughan T, Hackney J. et al. Long-term survival after transformation of an adrenocorticotropic hormone-secreting pituitary macroadenoma to a silent corticotroph pituitary carcinoma. World Neurosurg 2019; 122: 417-423