Pituitary carcinomas and aggressive pituitary tumours: merits and pitfalls of temozolomide treatment

Abstract

Summary Pituitary carcinomas are rare, accounting for about 0·2% of all pituitary tumours. They represent a challenge to clinical practice in both diagnosis and treatment. They may present initially as typical pituitary adenomas, with a delayed appearance of aggressive signs, or as aggressive tumours from the outset. Predicting the pituitary tumour behaviour remains difficult: increased mitotic, Ki‐67 and P53 indices might be associated with tumour aggression. The treatment of pituitary carcinomas and aggressive pituitary tumours includes surgery, adjuvant medical treatment, external beam radiotherapy and chemotherapy. Until recently, the treatment of pituitary carcinomas was mainly palliative and did not seem to increase overall survival. Recent case reports have detailed the successful use of temozolomide, an orally administered alkylating agent used to treat malignant gliomas, in the management of pituitary carcinomas and aggressive pituitary tumours. The outcome of treatment might depend on the expression of O 6 ‐methylguanine‐DNA methyltransferase (MGMT), a DNA repair enzyme that potentially interferes with drug efficacy. This review describes the clinical presentation and response to temozolomide in 44 patients with pituitary carcinomas or aggressive pituitary tumours reported in the literature. The results suggest that temozolomide should be considered a drug of major importance in the therapeutic algorithm of aggressive pituitary tumours and pituitary carcinomas. Because of the inconsistency of published data, MGMT expression should probably not be taken as a reason to deny these patients the potential benefit of temozolomide treatment, taking into account the paucity of other available treatments.

THERAPY OF ENDOCRINE DISEASE: The challenges in managing giant prolactinomas

“…In a recent review of available literature, Whitelaw and colleagues reported a good response to TMZ in 15 of 20 aggressive or metastatic prolactinomas and a strong association between negative immunostaining for methylguanine methyltransferase (MGMT) and response to therapy (94). However, such relationship between clinical response and MGMT staining has not been confirmed in all studies (92,93), and because of the very low number of patients with MGMT-positive prolactinoma reported to date (nZ2), candidates for TMZ treatment trial can hardly be selected on this basis.…”

“…Temozolomide (TMZ) is an oral alkylating agent inhibiting tumour cell growth, which has shown some efficacy in pituitary carcinomas and aggressive pituitary tumours (90,91,92,93). TMZ may be a salvage therapeutic option for patients with clinically aggressive giant prolactinomas that remain uncontrolled despite multiple conventional treatment modalities.…”

Giant GH-secreting pituitary adenomas: management of rare and aggressive pituitary tumors

“…Other options in the therapeutic armamentarium for patients with aggressive tumors resistant to the currently available medical treatments include the alkylating agent temozolomide that may be effective for aggressive pituitary tumors and pituitary carcinomas (32,33) resistant to the conventional treatments.…”

Clinical and Neurological Manifestations of Non-Functioning Pituitary Adenomas (NFPA). Is it ok to Suspect an Early Invasiveness?

“…The concepts of aggressiveness and invasion are different [12]; and are not interchangeable. Infrequently, the tumor tissue can affect, in its cavernous segment, the cranial nerves (CN) III, IV, V and VI, by compressing the adjacent neuronal tissue [13].…”