Temozolomide in aggressive pituitary tumours and pituitary carcinomas

Abstract

Survival for patients with aggressive pituitary tumours (APT) and pituitary carcinomas (PC) has significantly improved following the increasing use of temozolomide (TMZ) since the first reports of response in 2006. TMZ was established as first line chemotherapy for APT/PC in the 2018 ESE guidelines on the management of APT/PC. There is no controversy over its use as salvage therapy however there is increasing interest in exploring TMZ use earlier in the treatment algorithm for APT/PC. Overall response rates as reported in systematic reviews are around 40% but stable disease in another 25% illustrates the clinical effectiveness of TMZ. Response is higher among functional compared to non-functional tumours. Where maximal radiation thresholds have not been reached in a patient, combination radiotherapy and TMZ appears more effective. Whether combination TMZ and capecitabine (CAPTEM) offers increased benefit remains uncertain particularly given added toxicity. O6-methyl guanine DNA methyl transferase (MGMT) status is important in determining response to treatment, although examination via immunohistochemistry versus PCR-based promoter-methylation analysis remains somewhat controversial. Optimal duration of TMZ treatment has still not been determined although longer treatment courses have been associated with increased progression-free survival. Treatment options following disease progression after TMZ remain unclear but include a second course of TMZ, immunotherapy and targeted oncological agents such as bevacizumab and lapatinib as well as peptide receptor radionuclide treatment (PRRT). An experienced pituitary multidisciplinary team is essential to all management decisions in patients with APT/PC.