Endocrine Abstracts

Aggressive pituitary tumours, characterized by tumor recurrence and continued progression despite repeated treatments and pituitary carcinomas respond poorly to conventional therapies. The first reports describing the successful use of temozolomide (TMZ), an orally administered alkylating agent used to treat malignant gliomas, in the management of pituitary carcinomas were published in 2006. Following these single case reports small series of patients have detailed the successful use of TMZ, in the management of these pituitary tumours with an initial response in about 40–60% of cases some. Rapid tumour shrinkage or hormonal response to temozolomide treatment is usually observed within weeks after treatment initiation in responding patients. As a consequence, the lack of response after three cycles predicts further resistance to this treatment. Despite these encouraging results, complete tumour regression are exceptional, and secondary resistance are common during follow-up.

O6-methylguanine-DNA methyltransferase (MGMT), a DNA repair system involved in the cellular defence, represents the major mechanism of resistance to temozolomide. It has been suggested that MGMT expression may predict the tumour response to TMZ. Although results are conflicting among publication, it is accepted that low MGMT staining is associated with a high likelihood of treatment response. Owing to the rarity of the condition, contradictory published results, absence of prospective study and lack of other available medical treatments, MGMT status should probably not be taken as a reason to deny these patients the potential benefit of temozolomide. The expression of MLH1, MSH2, MSH6, three proteins of the DNA mismatch repair system, have been examined by IHC in three studies but these results are too preliminary and discordant to guide therapeutic options.

TMZ is not effective for all pituitary carcinomas or aggressive adenomas, and some tumours develop secondary resistance during follow-up. The development of new therapeutic options is therefore necessary. Some case reports suggest the need to associate temozolomide with other chemotherapeutic agents, while other preclinical and clinical studies suggest that new targeted therapies may be useful for controlling pituitary tumour growth.