Effects of CAPTEM (Capecitabine and Temozolomide) on a Corticotroph Carcinoma and an Aggressive Corticotroph Tumor.

Corticotroph carcinomas and aggressive corticotroph tumors can be resistant to conventional therapy, including surgery, radiotherapy, and medical treatment. Recent evidence suggests that temozolomide (an oral alkylating agent) administered with capecitabine (pro-drug of 5-fluorouracil) may improve progression-free survival in patients with high-risk corticotroph tumors and carcinomas. This led to the use of capecitabine and temozolomide (CAPTEM) in two patients, one with a corticotroph carcinoma and the other with an aggressive corticotroph tumor, as well the in vitro analysis of capecitabine and 5-fluorouracil on cell growth and hormone production. Both patients had previous surgical and radiation therapy. The first patient developed leptomeningeal spread 2 years after his radiation treatment. He had 12 cycles of CAPTEM, which resulted in tumor control associated with clinical and radiological improvement. Twenty-seven months later, CAPTEM was restarted for disease recurrence with ongoing tumor response. The second patient had a rapid tumor regrowth 2 years after his third surgical resection. He was treated with 12 cycles of CAPTEM, which led to tumor shrinkage with no tumor regrowth 22 months after cessation of therapy. Experiments using mouse ACTH-producing pituitary tumor AtT20 cells demonstrated that treatment with 5-fluorouracil in combination with temozolomide had an additive effect in reducing cell viability and ACTH production in the culture medium. Our patients and experimental data in AtT20 cells support CAPTEM as a potential treatment option for aggressive corticotroph tumors and carcinomas. However, a prospective clinical trial is required to determine whether CAPTEM is superior to temozolomide in the treatment of these tumors.