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Temozolomide and pasireotide treatment for aggressive pituitary adenoma: expertise at a tertiary care center

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Abstract

Aggressive pituitary adenomas (PAs) are clinically challenging for endocrinologists and neurosurgeons due to their locally invasive nature and resistance to standard treatment (surgery, medical or radiotherapy). Two pituitary-directed drugs have recently been proposed: temozolomide (TMZ) for aggressive PA, and pasireotide for ACTH-secreting PA. We describe the experience of our multidisciplinary team of endocrinologists, neurosurgeons, neuroradiologists, oncologists, otolaryngologists and pathologists with TMZ and pasireotide treatment for aggressive PAs in terms of their radiological shrinkage and genetic features. We considered five patients with aggressive PA, three of them non-secreting (two ACTH-silent and one becoming ACTH secreting), and two secreting (one GH and one ACTH). TMZ was administrated orally at 150–200 mg/m2 daily for 5 days every 28 days to all 5 patients, and 2 of them also received pasireotide 600–900 µg bid sc. We assessed the MRI at the baseline and during TMZ or pasireotide treatment. We also checked for MGMT promoter methylation and IDH, BRAF and kRAS mutations. Considering TMZ, two patients showed PA progression, one stable disease and two achieved radiological and clinical response. Pasireotide was effective in reducing hypercortisolism and mass volume, combined with TMZ in one case. Both treatments were generally well tolerated; one patient developed a grade 2 TMZ-induced thrombocytopenia. None of patients developed hypopituitarism while taking TMZ or pasireotide treatment. No genetic anomalies were identified in the adenoma tissue. TMZ and pasireotide may be important therapies for aggressive PA, alone or in combination.

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Authors and Affiliations

  1. Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, Via Ospedale Civile, 105, 35128, Padua, Italy

    Filippo Ceccato, Marco Boscaro & Carla Scaroni

  2. Department of Experimental and Clinical Oncology, Medical Oncology 1, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy

    Giuseppe Lombardi & Vittorina Zagonel

  3. Neuroradiology, University of Salerno, Salerno, Italy

    Renzo Manara

  4. Department of Otorhinolaryngology and Otologic Surgery, University-Hospital of Padova, Padua, Italy

    Enzo Emanuelli

  5. Neurosurgery, Department of Neurosciences DNS, University-Hospital of Padova, Padua, Italy

    Luca Denaro, Laura Milanese & Domenico D’Avella

  6. Surgical Pathology and Cytopathology Unit, Department of Medicine DIMED, University-Hospital of Padova, Padua, Italy

    Marina Paola Gardiman

  7. Immunology and Molecular Oncology, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy

    Roberta Bertorelle

  8. Neurosurgical Division, University-Hospital of Padova, Padua, Italy

    Massimo Scanarini

  9. Department of Biology, University of Padova, Padua, Italy

    Gianluca Occhi

Authors
  1. Filippo Ceccato
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  2. Giuseppe Lombardi
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  3. Renzo Manara
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  4. Enzo Emanuelli
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  5. Luca Denaro
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  6. Laura Milanese
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  7. Marina Paola Gardiman
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  9. Massimo Scanarini
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  10. Domenico D’Avella
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  11. Gianluca Occhi
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  12. Marco Boscaro
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  14. Carla Scaroni
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Correspondence to Filippo Ceccato.

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Ceccato, F., Lombardi, G., Manara, R. et al. Temozolomide and pasireotide treatment for aggressive pituitary adenoma: expertise at a tertiary care center. J Neurooncol 122, 189–196 (2015). https://doi.org/10.1007/s11060-014-1702-0

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  • DOI: https://doi.org/10.1007/s11060-014-1702-0

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