Background:

Temozolomide now has an established role in the treatment of aggressive pituitary tumours, but efficacy and safety data are limited to case reports and small series with short-term followup.   

Objective and Methods:

To report longer-term followup data on a large international cohort of patients with aggressive pituitary tumours treated with temozolomide. Clinical and pathological data were collected from clinicians in France, Australia, Italy, UK and USA.

Results:

A total of 34 patients (25 male, 9 female) of mean age 52.7 years (24 adenomas, 10 carcinomas) of various subtypes (ACTH 14, PRL 13, PRL-GH 3, GH 2, NF 2) were studied. These tumours were clinically and pathologically aggressive: average number of surgeries 2.5 and radiotherapy courses 1.5, Ki67 >3% in 20/24 cases. Patients underwent an average of 8.9 cycles of temozolomide with 60% experiencing no adverse effects. A hormonal response was reported in 61%, and radiological response in 67.7%, all by 3 months of treatment except one case. Seventeen patients with response have been followed for a mean of 36 months. One responder had disease progression at 6 months on temozolomide, the remaining 16 completed treatment. Six remain stable off treatment (6-15 months) whilst 10 have developed recurrence between 4 months and 4 years later. In 3 patients, a second course of temozolomide was not successful. When trialed, subsequent treatment with pasireotide, everolimus or alternative chemotherapy was not effective. Six of 22 (27%) responding patients have died, compared with 8 of 12 (67%) non-responding patients.

Conclusion:

Amongst this large cohort of aggressive pituitary tumours, the use of temozolomide is associated with high initial response rates, and commonly stable disease for many months after treatment cessation. Unfortunately, tumour re-growth ultimately occurs in the majority of responding patients. This study suggests that mortality may be reduced in patients who respond to temozolomide.