Temozolomide for aggressive ACTH pituitary tumors: failure of a second course of treatment.

Introduction: Temozolomide (TMZ) is an oral alkylating agent that has been used over the past 8 years to treat aggressive pituitary tumors resistant to conventional therapy. To date, only 25 patients treated with TMZ for ACTH producing pituitary tumors (14 adenomas and 11 carcinomas) have been reported.

Materials And Methods: We present a retrospective review of the medical records of three patients with aggressive ACTH producing adenomas treated with TMZ. In the three cases there was evidence of progression to conventional therapy before starting TMZ. We used the conventional scheme for the treatment of gliomas until completing 7, 12 and 6 cycles respectively. Reduction in tumor size was evident after the 3rd, 5th and 4th cycle of TMZ and progression free survival was 25, 19 and more than 12 months in the three patients respectively. Improvement of the ocular and visual symptoms was evident after the 4th cycle of treatment in all cases. Normalization of urinary free cortisol levels was achieved after the 3rd and 9th cycle in the two cases with hypercortisolism. Two of the three patients received a second course of treatment when the disease progressed but it did not stop tumor progression. The principal side effects were G3 neutropenia, G1 and G2 thrombocytopenia, G1 lymphopenia, asthenia and nausea.

Conclusion: The treatment with TMZ is effective and safe in patients with aggressive corticotrophin tumors resistant to conventional therapy. Nevertheless once the disease progresses, a second course of treatment does not seem to be effective.