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Temozolomide therapy in patients with aggressive pituitary adenomas or carcinomas

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Abstract

Temozolomide is effective in some patients with progressive pituitary adenoma or carcinoma. We report a survey study of Italian patients treated with Temozolomide because of aggressive pituitary adenoma or carcinoma resistant to standard therapies. Italian endocrinologists were surveyed and asked to participate into the study. A questionnaire was sent to all those who agreed and had used Temozolomide in at least one patient with pituitary tumor. Database was closed in December 2013. A literature review was also performed. Thirty-one patients were included into the analysis. Mean age at start of Temozolomide treatment was 58.3 ± 1.9 years (± standard error). Six of the 31 (19.4 %) Italian patients had a pituitary carcinoma. Twenty-five patients (80.6 %) had disease control during Temozolomide treatment, while 6 patients (19.4 %) had disease progression. Median follow-up after beginning Temozolomide was 43 months. Thirteen patients had tumor growth after stopping Temozolomide. The 2-year progression-free survival was 47.7 % (95 % CI 29.5–65.9 %), while the 2-year disease control duration was 59.1 % (95 % CI 39.1–79.1 %). Eleven patients died of progressive disease and other two patients of unrelated causes. The 2-year and 4-year overall survival rates were 83.9 % (95 % CI 70.7–97.1 %) and 59.6 % (95 % CI 40.0–79.2 %), respectively. Temozolomide is an additional effective therapeutic option for the treatment of aggressive pituitary tumors. The drug is well tolerated and causes few severe adverse effects. Recurrence of the tumor can occur after an initial positive response and usually portends a grim outcome.

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References

  1. Knizhnik AV, Roos WP, Nikolova T, Quiros S, Tomaszowski KH, Kaina B (2013) Survival and death strategies in glioma cells: autophagy, senescence and apoptosis triggered by a single type of temozolomide-induced DNA damage. PLoS ONE 8:e55665

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  2. Marchesi F, Turriziani M, Tortorelli G, Avvisati G, Torino F, De Vecchis L (2007) Triazene compounds: mechanism of action and related DNA repair systems. Pharmacol Res 56:275–287

    Article  PubMed  CAS  Google Scholar 

  3. Kesari S, Schiff D, Drappatz J, LaFrankie D, Doherty L, Macklin EA, Muikansky A, Santagata S, Ligon KL, Norden AD, Ciampa A, Bradshaw J, Levy B, Radakovic G, Ramakrishna N, Black PM, Wen PY (2009) Phase II study of protracted daily temozolomide for low-grade gliomas in adults. Clin Cancer Res 15:330–337

    Article  PubMed  CAS  Google Scholar 

  4. Stupp R, Hegi ME, Mason WP, van den Bent 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 randomized phase III study: 5-year analysis of the EORT-NCIC trial. Lancet Oncol 10:459–466

    Article  PubMed  CAS  Google Scholar 

  5. Ekeblad S, Sundin A, Janson ET, Welin S, Granberg D, Kindmark H, Dunder K, Koziovacki G, Orlefors H, Sigurd M, Oberg K, Eriksson B, Skogseid B (2007) Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors. Clin Cancer Res 13:2986–2991

    Article  PubMed  CAS  Google Scholar 

  6. Devata S, Kim EJ (2012) Neoadjuvant chemotherapy with capecitabine and temozolomide for unresectable pancreatic neuroendocrine tumor. Case Rep Oncol 5:622–626

    Article  PubMed  PubMed Central  Google Scholar 

  7. Fadul CE, Kominsky AL, Meyer LP, Kingman LS, Kinlaw WB, Rhodes CH, Eskey CJ, Simmons NE (2006) Long term response of pituitary carcinoma to temozolomide. J Neurosurg 105:621–626

    Article  PubMed  Google Scholar 

  8. Lim S, Shahinian H, Maya MM, Yong W, Heaney AP (2006) Temozolamide: a novel treatment for pituitary carcinoma. Lancet Oncol 7:518–520

    Article  PubMed  Google Scholar 

  9. McCormack AI, Wass JAH, Grossman AB (2011) Aggressive pituitary tumours: the role of temozolomide and the assessment of MGMT status. Eur J Clin Investig 41:1138–1148

    Article  Google Scholar 

  10. Syro LV, Ortiz L, Scheithauer BW, Lloyd R, Lau Q, Gonzales R, Uribe H, Cusimano M, Kovacs K, Horvath E (2011) Treatment of pituitary neoplasms with temozolomide. Cancer 117:454–462

    Article  PubMed  CAS  Google Scholar 

  11. Wen PY, MacDonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, Van den Bent MJ, Chang SM (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neurooncology working group. J Clin Oncol 10:1963–1972

    Article  Google Scholar 

  12. Curtò L, Torre ML, Ferraù F, Pitini V, Altavilla G, Granata F, Longo M, Hofland LJ, Trimarchi F, Cannavò S (2010) Temozolomide-induced shrinkage of a pituitary carcinoma causing cushing’s disease—report of a case and literature review. Sci World J 10:2132–2138

    Article  Google Scholar 

  13. Losa M, Mazza E, Terreni MR, McCormack A, Gill AJ, Motta M, Cangi MG, Talarico A, Mortini P, Reni M (2010) Salvage therapy with temozolomide in patients with aggressive or metastatic pituitary adenomas: experience in six cases. Eur J Endocrinol 163:843–851

    Article  PubMed  CAS  Google Scholar 

  14. Ceccato F, Lombardi G, Manara R, Emanuelli E, Denaro L, Milanese L, Gardiman MP, Bertorelle R, Scanarini M, D’Avella D, Occhi G, Boscaro M, Zagonel V, Scaroni C (2015) Temozolomide and pasireotide treatment for aggressive pituitary adenoma: expertise at a tertiary care center. J Neurooncol 122:189–196

    Article  PubMed  CAS  Google Scholar 

  15. Bengtsson D, Schrøder HD, Andersen M, Maiter D, Berinder K, Rasmussen UF, Rasmussen AK, Johannsson G, Hoybye C, van der Lely AJ, Petersson M, Ragnarsson O, Burman P (2015) 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 100:1689–1698

    Article  PubMed  CAS  Google Scholar 

  16. Bush ZM, Longtine JA, Cunningham T, Schiff D, Jane JA Jr, Vance ML, Thorner MO, Laws ER Jr, Lopes MB (2010) Temozolomide treatment for aggressive pituitary tumors: correlation of clinical outcome with O6-Methylguanine methyltransferase (MGMT) promoter methylation and expression. J Clin Endocrinol Metab 95:E280–E290

    Article  PubMed  Google Scholar 

  17. Gatenby RA (2009) A change of strategy in the war on cancer. Nature 459:508–509

    Article  PubMed  CAS  Google Scholar 

  18. Ortiz LD, Syro LV, Scheithauer BW, Rotondo F, Uribe H, Fadul CE, Horvath E, Kovacs K (2012) Temozolomide in aggressive pituitary adenomas and carcinomas. Clinics (Sao Paulo) 67(S1):119–123

    Article  Google Scholar 

  19. Whitelaw BC, Dworakowska D, Thomas NW, Barazi S, Riordan-Eva P, King AP, Hampton T, Landau DB, Lipscomb D, Buchanan CR, Gilbert JA, Aylwin SJB (2012) Temozolomide in the management of dopamine agonmist-resistant prolactinomas. Clin Endocrinol (Oxf) 76:877–886

    Article  CAS  Google Scholar 

  20. Raverot G, Sturm N, de Fraipont F, Muller M, Salenave S, Caron P, Chabre O, Chanson P, Cortet-Rudelli C, Assaker R, Dufour H, Gaillard S, François P, Jouanneau E, Passagia JG, Bernier M, Cornélius A, Figarella-Branger D, Trouillas J, Borson-Chazot F, Brue T (2010) Temozolomide treatment in aggressive pituitary tumors and pituitary carcinomas: a French multicenter experience. J Clin Endocrinol Metab 95:4592–4599

    Article  PubMed  CAS  Google Scholar 

  21. Mendola M, Passeri E, Ambrosi B, Corbetta S (2014) Multiple cerebral hemorrhagic foci from metastases during temozolomide treatment in a patient with corticotroph pituitary carcinoma. J Clin Endocrinol Metab 99:2623–2624

    Article  PubMed  CAS  Google Scholar 

  22. Kovacs K, Scheithauer BW, Lombardero M, McLendon RE, Syro LV, Uribe H, Ortiz LD, Penagos LC (2008) MGMT immunoexpression predicts responsiveness of pituitary tumors to temozolomide therapy. Acta Neuropathol 115:261–262

    Article  PubMed  Google Scholar 

  23. Hirohata T, Asano K, Ogawa Y, Takano S, Amano K, Isozaki O, Iwai Y, Sakata K, Fukuhara N, Nishioka H, Yamada S, Fujio S, Arita K, Takano K, Tominaga A, Hizuka N, Ikeda H, Osamura RY, Tahara S, Ishii Y, Kawamata T, Shimatsu A, Teramoto A, Matsuno A (2013) DNA mismatch repair protein (MSH6) correlated with the response 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 98:1130–1136

    Article  PubMed  CAS  Google Scholar 

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Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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Authors and Affiliations

  1. Department of Neurosurgery, Istituto Scientifico San Raffaele, Università Vita-Salute, Via Olgettina 60, 20132, Milan, Italy

    Marco Losa

  2. Section of Endocrinology, Department of Clinical and Experimental Medicine, Ospedale Cisanello, University of Pisa, Pisa, Italy

    Fausto Bogazzi

  3. Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy

    Salvo Cannavo & Lorenzo Curtò

  4. Endocrinology Unit, Department of Medicine, DIMED University-Hospital, Padua, Italy

    Filippo Ceccato & Carla Scaroni

  5. Endocrinologia, Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, Rome, Italy

    Laura De Marinis & Donato Iacovazzo

  6. Endocrinology, Barts and The London School of Medicine, Queen Mary University of London, London, UK

    Donato Iacovazzo

  7. Oncology Unit, Venetian Oncology Institute, Padua, Italy

    Giuseppe Lombardi

  8. Endocrinology and Diabetology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Department of Clinical Sciences and Community Health, University of Milano, Milan, Italy

    Giovanna Mantovani

  9. Department of Oncology, Istituto Scientifico San Raffaele, Università Vita-Salute, Milan, Italy

    Elena Mazza & Michele Reni

  10. Department of Radiation Oncology, Sant’Andrea Hospital, “La Sapienza” University, Rome, Italy

    Giuseppe Minniti

  11. Department of Endocrinology and Metabolic Disease, G.B. Morgagni Hospital, Forlì, Italy

    Maurizio Nizzoli

Authors
  1. Marco Losa
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  2. Fausto Bogazzi
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  3. Salvo Cannavo
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  4. Filippo Ceccato
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  5. Lorenzo Curtò
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  6. Laura De Marinis
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  7. Donato Iacovazzo
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  8. Giuseppe Lombardi
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  9. Giovanna Mantovani
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  10. Elena Mazza
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  11. Giuseppe Minniti
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  12. Maurizio Nizzoli
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  13. Michele Reni
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  14. Carla Scaroni
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Correspondence to Marco Losa.

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Losa, M., Bogazzi, F., Cannavo, S. et al. Temozolomide therapy in patients with aggressive pituitary adenomas or carcinomas. J Neurooncol 126, 519–525 (2016). https://doi.org/10.1007/s11060-015-1991-y

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  • DOI: https://doi.org/10.1007/s11060-015-1991-y

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