Thursday, August 6, 2009

Temozolomide treatment of a pituitary carcinoma and two pituitary macroadenomas resistant to conventional therapy

Casper Hagen, Henrik Schroeder, Steinbjorn Hansen, Claus Hagen and Marianne Andersen

C Hagen, Department of Endocrinology, Odense University Hospital, Odense C, Denmark
H Schroeder, Department of Pathology, Odense University Hospital, Odense C, Denmark
S Hansen, Department of Oncology, Odense University Hospital, Odense C, Denmark
C Hagen, Department of Endocrinology, Odense University Hospital, Odense C, Denmark
M Andersen, Department of Endocrinology, Odense University Hospital, Odense C, Denmark

Correspondence: Casper Hagen, Email: casperhagen@gmail.com

Abstract

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.

DESIGN: We present three patients with pituitary tumours treated with TMZ. One tumour was initially a macroprolactinoma that developed into a mixed GH and PRL- 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 (NFA) (patient C), were highly invasive. The three patients suffered from extensive tumour mass effects, and all tumours were resistant to conventional treatment.

METHOD: TMZ, 150-200 mg/m2 of body surface area was administered orally for 5 days during each 28 day cycle.

RESULT: 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). 3 years after terminating treatment, 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.

CONCLUSION: 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.

From http://www.eje.org/cgi/content/abstract/EJE-09-0389v1