Temozolomide treatment of a pituitary carcinoma and two pituitary macroadenomas resistant to conventional therapy.
OBJECTIVE
Aggressive pituitary tumours may be difficult to treat. Temozolomide (TMZ) is an alkylating cytostaticum. In a small number of cases, TMZ therapy has been reported to reduce pituitary tumour size and hormone hypersecretion.


METHODS
We present three patients with pituitary tumours treated with TMZ. One tumour was initially a macroprolactinoma that developed into a mixed GH- and prolactin-secreting carcinoma (patient A). To our knowledge, this is the first published in English literature. Two adenomas, a macroprolactinoma (patient B) and a clinically non-functioning pituitary adenoma (patient C), were highly invasive. The three patients suffered from extensive tumour mass effects, and all tumours were resistant to conventional treatment.


METHODS
TMZ, 150-200 mg/m(2) of body surface area was administered orally for 5 days during each 28-day cycle.


RESULTS
During TMZ therapy, tumour sizes were significantly reduced, hormone levels normalized and symptoms of mass effects decreased in all three cases. The carcinoma was treated from 2004 to 2006 (23 months). Three years after the terminating treatment, the tumour has not regrown and hormone levels are normalized. Immunohistochemical staining for methylguanine DNA methyltransferase (MGMT) was negative in two patients (A and B), and in one patient (C) a few nuclei stained positive.


CONCLUSIONS
TMZ therapy significantly decreased tumour volume, hormone hypersecretion and symptoms in all three patients, corresponding to the pathological findings regarding MGMT. TMZ therapy may be a new option for the treatment of resistant pituitary adenomas.
Hagen
C
C
Department of Endocrinology, Odense University Hospital, 5000 Odense C, Denmark. casperhagen@gmail.com
Schroeder
H D
HD
Hansen
S
S
Hagen
C
C
Andersen
M
M
D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D006728:Hormones / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism; D016612:Paraffin Embedding; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000473:pathology; D049268:Positron-Emission Tomography; D011388:Prolactin / Q000097:blood; D015175:Prolactinoma / Q000188:drug therapy* / Q000473:pathology; D000077204:Temozolomide; D055815:Young Adult
D018906:Antineoplastic Agents, Alkylating; D006728:Hormones; D003606:Dacarbazine; D011388:Prolactin; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide