Endocrine Abstracts

Background: Temozolomide is an alkylating chemoterapic agent that ties a methyl to guanine, causing a base-pair mismatch and a DNA damage, resulting in cell death. Due to its lipophilic nature and its ability to cross the blood-brain barrier, this drug was originally used for malignant gliomas and later for aggressive pituitary tumors and carcinomas. Temozolomide is now recommended as first-line chemotherapy by the recently published ESE Clinical Practice Guidelines. Here we present our experience with temozolomide in three patients with aggressive and invasive ACTH-secreting pituitary tumors.

Patients: PT1 (female, 65 years-old) after two surgical interventions (pathology: ACTH-staining pituitary adenoma) and several medical therapies, underwent a severe relapse in hypercortisolism associated with worsening of general conditions and increase in tumor remnants. Temozolomide was started, leading to a sudden control of hypercortisolism. One month later PT1 underwent gamma-knife radiosurgery. Temozolomide was withdrawn after five cycles for hematological side effects. After 5 years, hypercortisolism is still in remission and a signisficant reduction in tumor remnants was documented. PT2 (male, 50 years-old) a few months after pituitary surgery (pathology: ACTH-staining pituitary atypical adenoma, Ki-67>4–5%) underwent severe relapse of hypercortisolism; temozolomide (in association with capecitabine, ‘CAPTEM’) was started with pasireotide, leading to a rapid control of disease. Six months later PT2 was treated with external-beam radiotherapy. CAPTEM was withdrawn after 12 cycles, pasireotide was withdrawn 1 month later and hydrocortisone was started for the development of hypocortisolism. PT3 (male, 50 years-old) had been treated with four surgical interventions and a course of external-beam radiotherapy. MRI revealed tumor remnants in the right cavernous sinus and above the sellar region, compressing the right subnuclear and temporo-mesial regions and the right-inferior cerebellar pedunculus; furthermore a meningeal metastasis was spotted above the clivus, protruding in the prebulbar cysterna. PT3 underwent 15 cycles of CAPTEM gaining an overall good control in hypercortisolism and a reduction in tumor and metastasis size. PT3 remained in remission of disease for 3 years.

Conclusion: Therapy with temozolomide (alone or in combination with capecitabine) was highly effective in controlling hypercortisolism in the short term; moreover, in association with radiotherapy, temozolomide proved effective in reducing pituitary mass and prolonging remission of disease. It can be considered for different categories of patients: patients (as PT1) with severe/repeated recurrence of disease; patients (as PT2) with histologically aggressive tumors in whom surgery was not complete and hypercortisolism relapses; patients (as PT3) with pituitary carcinoma.