The role of temozolomide in the treatment of aggressive pituitary adenomas and pituitary carcinomas

Except for aggressive prolactinomas, which are could be treated with dopamin agonists, surgery is the first-line treatment option for most aggressive pituitary adenomas, but usually, due to their size, invasion of surrounding tissues, and high frequency of regrowth, they are difficult to treat with standard treatment paradigms, including surgery and radiotherapy. Pituitary carcinomas are rare tumours, and are defined by aggressive adenomas with brain and/or systemic metastasis. These carcinomas are highly aggressive, resistant to surgery, radiotherapy and systemic chemotherapy, and are associated with poor survival. Recently, temozolomide, an alkylating imidazoltetrazine derivative, chemically related to dacarbazine, have been used successfully in the management of aggressive pituitary adenomas and pituitary carcinomas, resistant to conventional treatments. O-6 methylguanine DNA methyltransferase, a DNA repair enzyme, have been demonstrated to be associated with sensitivity to temozolomide. Temozolomide is considered to be a novel drug in the treatment of aggressive
pituitary adenomas and pituitary carcinomas, with few side effects, however it may cause serious side effects and proper follow-up of patients is essential.

Agresif hipofiz adenomlarý ve hipofiz karsinomlarýn tedavisinde Temozolomide’in rolü

Dopamin agonistleriyle tedavi edilebilen agresif prolaktinomalar dýþýndaki agresif hipofiz adenomlarýnda ilk tedavi seçeneði cerrahidir. Fakat sýklýkla bu tümörlerin çaplarýnýn büyük olmasý, çevre dokulara invazyon yapmasý ve nüks oranlarýnýn yüksek olmasý nedeniyle cerrahi ve radyoterapi gibi standart tedaviler yetersiz kalmaktadýr. Hipofiz karsinomlarý ise nadir görülen tümörler olup agresif hipofiz adenomlarýnýn kraniyospinal veya sistemik metastaz yapmalarý þeklinde tanýmlanýr. Bu karsinomlar oldukça invaziv olup cerrahi, radyoterapi ve kemoterapiye dirençlidirler ve prognozlarý kötüdür. Son zamanlarda, kimyasal olarak dakarbazin ile iliþkili, imidazoltetrazin derivesi alkilleyici bir ajan olan temozolomid agresif hipofiz adenomlarý ve hipofiz karsinomlarýnýn tedavisinde
baþarýyla kullanýlmýþtýr. O-6 metilguanin DNA metiltransferaz bir DNA tamir enzimi olup temozolomid tedavisine yanýtta rolü olduðu gösterilmiþtir. Temezolomid tedavisinin genellikle hafif derecede yan etkileri olmakla birlikte bazen ciddi yan etkilere neden olabileceðinden yakýn takip gerekmektedir. Temozolomid, konvansiyonel tedavilere yanýtsýz ve O-6 metilguanin DNA metiltransferaz düzeyi düþük olan agresif hipofiz adenom ve hipofiz karsinomlarýnda alternatif bir tedavi ajaný olarak düþünülebilir.