Early Recognition and Initiation of Temozolomide Chemotherapy for Refractory, Invasive Pituitary Macroprolactinoma with Long-Term Sustained Remission

OBJECTIVE: Invasive, medically refractory, and multiply recurrent pituitary adenomas pose a rare, but nevertheless significant, challenge for conventional management modalities. Temozolomide (TMZ) has been reported to be useful as an adjunctive treatment for some patients. We describe the efficacy of TMZ when used early in the management of invasive prolactinoma. CASE DESCRIPTION: A 56-year-old man presented with an invasive, refractory macroprolactinoma for which long-term dopamine agonists, stereotactic radiosurgery, and multiple transsphenoidal surgical resections had failed. He had experienced persistent hyperprolactinemia and tumor progression. Thus, TMZ was started. During the 11 cycles of TMZ therapy, the patient's prolactin level decreased from 696 ng/mL to 15.2 ng/mL, with a > 90% decrease in tumor size. Nearly 6 years after discontinuing chemotherapy, the patient remained in sustained remission (prolactin level, 3.1 ng/mL) requiring only 1.5 mg of cabergoline weekly, without radiographic or clinical evidence of tumor recurrence. CONCLUSIONS: We conclude that TMZ can be efficacious in the management of medically and surgically refractory, invasive atypical prolactinomas, resulting in normalization of the prolactin levels and control of the tumor size. We encourage the inclusion of TMZ in the management of refractory, recurrent, and invasive prolactinomas, as a fourth-line treatment strategy, after dopamine agonist treatment, transsphenoidal resection, and radiation therapy. We especially advocate the early use of TMZ for aggressive and otherwise refractory prolactinomas.