Temozolomide for corticotroph pituitary adenomas refractory to standard therapy

To highlight the potential of temozolomide (TMZ) to induce rapid tumor regression in patients with aggressive corticotroph adenomas (CA) that are refractory to surgery and radiation therapy and to review use of TMZ in other pituitary tumors. We present a case of a 56-year-old male with a 3 cm CA treated with transphenoidal surgery (TSS) and conventional radiotherapy in the same year. His hypercortisolemia recurred 11 years later with rapid tumor growth (to 4.2 × 2.5 cm) and he underwent a second TSS with good resection. The tumor recurred 6 months later with ophthalmoplegia. Over 16 months he underwent an additional three surgeries (two TSS, one craniotomy) and repeated conventional radiotherapy. Ki67 staining index on surgical specimens was 5-6%. Temozolomide is an oral alkylating agent approved for glioblastoma multiforme treatment that has only recently shown promise in treating some pituitary tumors. In this patient TMZ was started at 150 mg/m²/day, titrated to 200 mg/m ²/day, taken 5 days per month. The only significant side effect was moderate nausea. After 10 weeks, the tumor showed a remarkable 60% regression with objective improvement in ophthalmoplegia. Treatment of aggressive CAs represents a therapeutic challenge and in some cases surgical debulking and radiotherapy are of limited success. Few reports of CAs responsive to TMZ have been reported in the literature. To our knowledge, this case represents the most rapid robust CA shrinkage response reported to date. Further randomized clinical trials of TMZ in the treatment of aggressive pituitary adenomas are warranted.