High response rates and prolonged survival in patients with corticotroph pituitary tumors and refractory Cushing disease from capecitabine and temozolomide (CAPTEM): a case series

Brad E Zacharia, Anthony P Gulati, Jeffrey N Bruce, Arthur S Carminucci, Sharon L Wardlaw, Markus Siegelin, Helen Remotti, Angela Lignelli, Robert L Fine
Neurosurgery 2014, 74 (4): E447-55; discussion E455

BACKGROUND AND IMPORTANCE: Rarely, corticotrophic pituitary tumors take on an aggressive form characterized by rapid growth, invasion into local structures, compression of cranial nerves, and possible spread to distant sites. When conventional surgery, radiation therapy, and hormones fail to control progression and symptoms, alternative therapies are needed. A novel chemotherapeutic regimen of capecitabine and temozolomide (CAPTEM), originally designed in our laboratory, demonstrated dramatic antineoplastic effects against corticotrophic pituitary tumors.

CLINICAL PRESENTATION: We present a case series of 4 patients with aggressive, adrenocorticotrophic hormone--producing pituitary tumors who had previously depleted all surgical, radiation, and hormonal therapies and were then treated with CAPTEM. Dramatic clinical improvements in neurological deficits and Cushing symptoms were evident in all patients after treatment was initiated. Confirmed by radiographic imaging, 2 of 4 patients demonstrated complete regression of disease, 1 patient had a 75% regression, and the fourth patient has ongoing stable disease for > 4.5 years at the time of this writing. Immunohistochemical analysis of patients' tumor samples showed low O-methyguanyl methyltransferase expression and adequate levels of mismatch repair enzymes (MLH-1, MSH-2, MSH-6, and PMS-2), which are important for the in vivo efficacy of CAPTEM.

CONCLUSION: This is the first report of prolonged antitumor response to and radiographic complete remissions as a result of CAPTEM in patients with aggressive pituitary tumors who had exhausted all other therapies.

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