Salvage therapy with temozolomide in patients with aggressive or metastatic pituitary adenomas: experience in six cases.
OBJECTIVE
The prognosis of either pituitary carcinoma or aggressive pituitary adenoma resistant to standard therapies is poor. We assessed the efficacy of treatment with temozolomide, an oral second-generation alkylating agent, in a consecutive series of six patients with aggressive pituitary adenomas.


METHODS
This was a 1-year prospective study of temozolomide therapy in six consecutive patients with pituitary carcinoma (one case) or atypical pituitary adenoma (five cases) resistant to standard therapies. There were three males and three females. Age at enrollment ranged between 52 and 64 years. Temozolomide was given orally at a dose of 150-200 mg/m(2) per day for 5 days every 4 weeks for a maximum of 12 cycles.


METHODS
Response assessment was based on measurable change in tumor size, as assessed on magnetic resonance imaging, and hormone levels. Response was defined as reduction of at least 50% of tumor size and hormone levels.


RESULTS
Four patients completed the 12 cycles of temozolomide treatment, as planned. Two patients stopped the drug after 3 and 6 months respectively because of the progression of disease. Two patients responded to temozolomide, while the remaining two patients had stable disease. Immunohistochemistry for O(6)-methylguanine-DNA methyltransferase (MGMT) in tumor sample showed a partial association with treatment response.


CONCLUSIONS
Temozolomide treatment has a wide range of efficacy in patients with pituitary carcinoma or locally aggressive pituitary adenoma. Positive staining for MGMT seems likely to predict a lower chance of response.
Losa
Marco
M
Pituitary Unit, Department of Neurosurgery, Istituto Scientifico San Raffaele, Università Vita-Salute, Via Olgettina 60, 20132 Milano, Italy. losa.marco@hsr.it
Mazza
Elena
E
Terreni
Maria Rosa
MR
McCormack
Ann
A
Gill
Anthony J
AJ
Motta
Micaela
M
Cangi
Maria Giulia
MG
Talarico
Anna
A
Mortini
Pietro
P
Reni
Michele
M
D000236:Adenoma / Q000188:drug therapy* / Q000201:enzymology; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy / Q000201:enzymology; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D011446:Prospective Studies; D016879:Salvage Therapy; D000077204:Temozolomide
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide