Download PDF
Exp Clin Endocrinol Diabetes 2021; 129(03): 186-193
DOI: 10.1055/a-1331-6939
Review

Medical Therapy of Aggressive Pituitary Tumors

Stephan Petersenn
1   ENDOC Center for Endocrine Tumors, Hamburg, Germany
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

The rare aggressive pituitary adenoma presents a special challenge, due to the heterogenous presentation of the disease. The prognosis of aggressive pituitary adenomas has been improved due to recent studies demonstrating clinically-relevant efficacy of temozolomide, which is now considered first-line chemotherapy. However, there is limited data on second-line therapies in patients with treatment failure. This review presents a summary on the potential of medical therapies in aggressive pituitary tumors.

Key words

carcinoma - chemotherapy - temozolomide - bevacizumab - tyrosine kinase inhibitor - everolimus - cyclin-dependent kinase inhibitor - checkpoint inhibitor


Publication History

Received: 09 October 2020
Received: 01 December 2020

Accepted: 07 December 2020

Article published online:
09 March 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Saeger W, Ludecke 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
    CrossrefPubMedGoogle Scholar
  • 2 Raverot G, Burman P, McCormack A. et al. European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas. Eur J Endocrinol 2018; 178: G1-G24
    CrossrefPubMedGoogle Scholar
  • 3 Casanueva FF, Barkan AL, Buchfelder M. et al. Criteria for the definition of Pituitary Tumor Centers of Excellence (PTCOE): A Pituitary Society Statement. Pituitary 2017; 20: 489-498
    CrossrefPubMedGoogle Scholar
  • 4 Miermeister CP, Petersenn S, Buchfelder M. et al. Histological criteria for atypical pituitary adenomas - data from the German pituitary adenoma registry suggests modifications. Acta Neuropathol Commun 2015; 3: 50
    CrossrefPubMedGoogle Scholar
  • 5 Noh TW, Jeong HJ, Lee MK. et al. Predicting recurrence of nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 2009; 94: 4406-4413
    CrossrefPubMedGoogle Scholar
  • 6 Widhalm G, Wolfsberger S, Preusser M. et al. Residual nonfunctioning pituitary adenomas: prognostic value of MIB-1 labeling index for tumor progression. J Neurosurg 2009; 111: 563-571
    CrossrefPubMedGoogle Scholar
  • 7 Trouillas J, Roy P, Sturm N. et al. A new prognostic clinicopathological classification of pituitary adenomas: A multicentric case-control study of 410 patients with 8 years post-operative follow-up. Acta Neuropathol 2013; 126: 123-135
    CrossrefPubMedGoogle Scholar
  • 8 Asioli S, Righi A, Iommi M. et al. Validation of a clinicopathological score for the prediction of post-surgical evolution of pituitary adenoma: Retrospective analysis on 566 patients from a tertiary care centre. Eur J Endocrinol 2019; 180: 127-134
    CrossrefPubMedGoogle Scholar
  • 9 Guaraldi F, Zoli M, Righi A. et al. A practical algorithm to predict postsurgical recurrence and progression of pituitary neuroendocrine tumours (PitNET)s. Clinical Endocrinology 2020; 93: 36-43
    CrossrefPubMedGoogle Scholar
  • 10 Burman P, Lamb L, McCormack A. Temozolomide therapy for aggressive pituitary tumours - current understanding and future perspectives. Rev Endocr Metab Disord 2020; 21: 263-276
    CrossrefPubMedGoogle Scholar
  • 11 Ji Y, Vogel RI, Lou E. Temozolomide treatment of pituitary carcinomas and atypical adenomas: systematic review of case reports. Neuro-Oncology Practice 2016; 3: 188-195
    CrossrefPubMedGoogle Scholar
  • 12 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
    CrossrefPubMedGoogle Scholar
  • 13 Lizzul L, Lombardi G, Barbot M. et al. Long-course temozolomide in aggressive pituitary adenoma: real-life experience in two tertiary care centers and review of the literature. Pituitary 2020; 23: 359-366
    CrossrefPubMedGoogle Scholar
  • 14 Minniti G, Paolini S, Rea MLJ. et al. Stereotactic reirradiation with temozolomide in patients with recurrent aggressive pituitary tumors and pituitary carcinomas. J Neurooncol 2020; 149: 123-130
    CrossrefPubMedGoogle Scholar
  • 15 Heaney AP. Clinical review: Pituitary carcinoma: Difficult diagnosis and treatment. J Clin Endocrinol Metab 2011; 96: 3649-3660
    CrossrefPubMedGoogle Scholar
  • 16 Cornell RF, Kelly DF, Bordo G. et al. Chemotherapy-induced regression of an adrenocorticotropin-secreting pituitary carcinoma accompanied by secondary adrenal insufficiency. Case Reports in. Endocrinology 2013; 2013: 1-10
    PubMedGoogle Scholar
  • 17 AbdelBaki MS, Waguespack SG, Salceda V. et al. Significant response of pituitary carcinoma to carboplatin, leucovorin and fluorouracil chemotherapy: A pediatric case report and review of the literature. Journal of Neuro-Oncology 2017; 135: 213-215
    CrossrefPubMedGoogle Scholar
  • 18 Kaltsas GA, Mukherjee JJ, Plowman PN. et al. The role of cytotoxic chemotherapy in the management of aggressive and malignant pituitary tumors. J Clin Endocrinol Metab 1998; 83: 4233-4238
    CrossrefPubMedGoogle Scholar
  • 19 Lasolle H, Vasiljevic A, Borson-Chazot F. et al. Pasireotide: A potential therapeutic alternative for resistant prolactinoma. Ann Endocrinol (Paris) 2019; 80: 84-88
    CrossrefPubMedGoogle Scholar
  • 20 Coopmans EC, van Meyel SWF, Pieterman KJ. et al. Excellent response to pasireotide therapy in an aggressive and dopamine-resistant prolactinoma. Eur J Endocrinol 2019; 181: K21-K27
    CrossrefPubMedGoogle Scholar
  • 21 Raverot G, Vasiljevic A, Jouanneau E. et al. Confirmation of a new therapeutic option for aggressive or dopamine agonist-resistant prolactin pituitary neuroendocrine tumors. European Journal of Endocrinology 2019; 181: C1-C3
    CrossrefPubMedGoogle Scholar
  • 22 Ortiz LD, Syro LV, Scheithauer BW. et al. Anti-VEGF therapy in pituitary carcinoma. Pituitary 2012; 15: 445-449
    CrossrefPubMedGoogle Scholar
  • 23 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
    CrossrefPubMedGoogle Scholar
  • 24 Rotman LE, Vaughan TB, Hackney JR. 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
    CrossrefPubMedGoogle Scholar
  • 25 Dutta P, Reddy KS, Rai A. et al. Surgery, octreotide, temozolomide, bevacizumab, radiotherapy, and pegvisomant treatment of an aip mutation-positive child. J Clin Endocrinol Metab 2019; 104: 3539-3544
    CrossrefPubMedGoogle Scholar
  • 26 Osterhage K, Rotermund R, Droste M et al. Bevacizumab in aggressive pituitary adenomas – experience with 3 patients. ECED 2020in print
    PubMed
  • 27 Wang Y, He Q, Meng X. et al. Apatinib (YN968D1) and temozolomide in recurrent invasive pituitary adenoma: Case report and literature review. World Neurosurg 2019; 124: 319-322
    CrossrefPubMedGoogle Scholar
  • 28 Jouanneau E, Wierinckx A, Ducray F. et al. New targeted therapies in pituitary carcinoma resistant to temozolomide. Pituitary 2012; 15: 37-43
    CrossrefPubMedGoogle Scholar
  • 29 Donovan LE, Arnal AV, Wang SH. et al. Widely metastatic atypical pituitary adenoma with mTOR pathway STK11(F298L) mutation treated with everolimus therapy. CNS Oncol 2016; 5: 203-209
    CrossrefPubMedGoogle Scholar
  • 30 Zhang D, Way JS, Zhang X. et al. Effect of Everolimus in Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas. J Clin Endocrinol Metab 2019; 104: 1929-1936
    CrossrefPubMedGoogle Scholar
  • 31 Cooper O, Mamelak A, Bannykh S. et al. Prolactinoma ErbB receptor expression and targeted therapy for aggressive tumors. Endocrine 2014; 46: 318-327
    CrossrefPubMedGoogle Scholar
  • 32 Simpson DJ, Frost SJ, Bicknell JE. et al. Aberrant expression of G(1)/S regulators is a frequent event in sporadic pituitary adenomas. Carcinogenesis 2001; 22: 1149-1154
    CrossrefPubMedGoogle Scholar
  • 33 Anderson E, Heller RS, Lechan RM. et al. Regression of a nonfunctioning pituitary macroadenoma on the CDK4/6 inhibitor palbociclib: Case report. Neurosurg Focus 2018; 44: E9
    CrossrefPubMedGoogle Scholar
  • 34 Lin AL, Jonsson P, Tabar V. et al. Marked Response of a Hypermutated ACTH-Secreting Pituitary Carcinoma to Ipilimumab and Nivolumab. J Clin Endocrinol Metab 2018; 103: 3925-3930
    CrossrefPubMedGoogle Scholar
  • 35 Sol B, de Filette JMK, Awada G. et al. Immune checkpoint inhibitor therapy for ACTH-secreting pituitary carcinoma: A new emerging treatment. Eur J Endocrinol 2021; 184: K1-K5
    CrossrefPubMedGoogle Scholar
  • 36 Duhamel C, Ilie MD, Salle H. et al. Immunotherapy in corticotroph and lactotroph aggressive tumors and carcinomas: Two case reports and a review of the literature. J Pers Med 2020; 10: 88
    CrossrefPubMedGoogle Scholar
  • 37 Caccese M, Barbot M, Ceccato F. et al. Rapid disease progression in patient with mismatch-repair deficiency pituitary ACTH-secreting adenoma treated with checkpoint inhibitor pembrolizumab. Anticancer Drugs 2020; 31: 199-204
    CrossrefPubMedGoogle Scholar
  • 38 Losa M, Mazza E, Terreni MR. et al. Salvage therapy with temozolomide in patients with aggressive or metastatic pituitary adenomas: Experience in six cases. Eur J Endocrinol 2010; 163: 843-851
    CrossrefPubMedGoogle Scholar
  • 39 Bush ZM, Longtine JA, Cunningham T. et al. Temozolomide treatment for aggressive pituitary tumors: Correlation of clinical outcome with O(6)-methylguanine methyltransferase (MGMT) promoter methylation and expression. J Clin Endocrinol Metab 2010; 95: E280-E290
    CrossrefPubMedGoogle Scholar
  • 40 Raverot G, Sturm N, de Fraipont F. et al. Temozolomide treatment in aggressive pituitary tumors and pituitary carcinomas: A french multicenter experience. J Clin Endocrinol Metab 2010; 95: 4592-4599
    CrossrefPubMedGoogle Scholar
  • 41 Hirohata T, Asano K, Ogawa Y. et al. DNA mismatch repair protein (MSH6) correlated with the responses of atypical pituitary adenomas and pituitary carcinomas to temozolomide: the national cooperative study by the Japan Society for Hypothalamic and Pituitary Tumors. J Clin Endocrinol Metab 2013; 98: 1130-1136
    CrossrefPubMedGoogle Scholar
  • 42 Bengtsson D, Schroder HD, Andersen M. et al. Long-term outcome and MGMT as a predictive marker in 24 patients with atypical pituitary adenomas and pituitary carcinomas given treatment with temozolomide. J Clin Endocrinol Metab 2015; 100: 1689-1698
    CrossrefPubMedGoogle Scholar
  • 43 Ceccato F, Lombardi G, Manara R. et al. Temozolomide and pasireotide treatment for aggressive pituitary adenoma: expertise at a tertiary care center. J Neurooncol 2015; 122: 189-196
    CrossrefPubMedGoogle Scholar
  • 44 Bruno OD, Juárez-Allen L, Christiansen SB. et al. Temozolomide therapy for aggressive pituitary tumors: Results in a small series of patients from Argentina. Int J of Endocrinol 2015; 2015: 1-8
    CrossrefPubMedGoogle Scholar
  • 45 Losa M, Bogazzi F, Cannavo S. et al. Temozolomide therapy in patients with aggressive pituitary adenomas or carcinomas. Journal of Neuro-Oncology 2016; 126: 519-525
    CrossrefPubMedGoogle Scholar
  • 46 Lasolle H, Cortet C, Castinetti F. et al. Temozolomide treatment can improve overall survival in aggressive pituitary tumors and pituitary carcinomas. Eur J Endocrinol 2017; 176: 769-777
    CrossrefPubMedGoogle Scholar
  • 47 Jordan JT, Miller JJ, Cushing T. et al. Temozolomide therapy for aggressive functioning pituitary adenomas refractory to surgery and radiation: a case series. Neurooncol Pract 2018; 5: 64-68
    PubMedGoogle Scholar
  • 48 Elbelt U, Schlaffer SM, Buchfelder M. et al. Efficacy of temozolomide therapy in patients with aggressive pituitary adenomas and carcinomas-A German survey. J Clin Endocrinol Metab 2020; 105: e660-e675
    CrossrefPubMedGoogle Scholar
  • 49 Petersenn S. Management of aggressive pituitary tumors – A 2019 update. Horm Metab Res 2019; 51: 755-764
    Article in Thieme ConnectPubMedGoogle Scholar