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Skull Base Brain Tumor Research

Temodar: Novel Treatment for Pituitary Carcinoma
By Yong Zhu, Hrayr Shahinian, Behrooz Hakimian, Vivien Bonert, Stephen Lim, Anthony Heaney

Although pituitary tumors are common, pituitary carcinoma is extremely rare, occurring in 0.1-0.2% of cases. Patients with systemic metastases show poorer survival than those with craniospinal spread, and most die within a year of diagnosis. We describe a 65 year-old male who presented with headache and erectile dysfunction in 1987 with an elevated serum prolactin (PRL) level of 200 ng/ml. Bromocriptine treatment improved his symptoms, and normalized serum PRL level. In 1998 he represented with sudden onset headache, vomiting, pre-syncope, and hypopituitarism. MRI revealed pituitary fossa hemorrhage, serum PRL was elevated at 2,000 ng/ml, and pituitary apoplexy was diagnosed. Following transsphenoidal surgery, serum PRL level fell to 600 ng/ml, and after a further endoscopic resection of residual tumor, serum PRL again normalized. One year later, serum PRL rose to 232 ng/ml, he commenced cabergoline treatment (0.5 mg twice weekly), gradually increasing to 3 mg twice weekly. However, serum PRL continued to rise (2,656 ng/ml), the patient underwent further pituitary tumor debulking, at which time, the optic nerve was noted to be infiltrated with tumor. Following representation with neck pain one year later, he underwent two additional resections of skull-base metastatic droplet tumors, and received pituitary and cranial radiation (5,200 Gy), as cranio-cervical junctional tumor was compressing the medulla. Despite these aggressive measures, extensive residual pituitary tumor remained in the brain-stem and pituitary fossa region, and serum PRL increased further to 7,300 ng/ml. He became increasingly incapacitated, and hospice care was considered. In light of his rapidly progressive life-threatening pituitary tumor, he was commenced on the novel alkylating agent, temozolomide (Temodar), given in monthly cycles (400 mg PO qd x 5 days). One month following temozolomide treatment, serum prolactin level reduced to 6,722 ng/ml, and then fell progressively over the ensuing 12 month treatment period to 219 ng/ml, without significant side effects. Serial MRI of the pituitary fossa and cranio-cervical tumor masses also demonstrated significant tumor shrinkage (~30%). 15 months following initiation of temozolomide therapy, pituitary fossa and cranio-cervical tumor masses and serum PRL has remained stable, and he is now fully ambulatory. We propose temozolomide treatment as a novel therapeutic option in managing these rare cases of locally advanced pituitary carcinoma.