Status of temozolomide use without insurance coverage in patients with aggressive pituitary neuroendocrine tumors

The 2017 World Health Organization classification described aggressive pituitary neuroendocrine tumor (PitNET) as "a tumor with strong invasiveness and rapid growth, which is difficult to treat with surgery, radiation therapy, or drug therapy," which remains a challenge in the treatment of pituitary tumors. Currently, temozolomide (TMZ) is the first-line treatment for aggressive PitNET. However, it is not yet covered by insurance in Japan. Additionally, O6-Methylguanine-DNA Methyltransferase (MGMT) expression can lead to treatment resistance, further complicating treatment selection. We previously demonstrated the effectiveness of combination therapy with capecitabine (CAPTEM) in several cases of aggressive PitNETs. The present study described our experiences with TMZ in 13 patients with aggressive PitNETs (including four patients administered CAPTEM). Pathological examination revealed eight corticotroph, four lactotroph, and one somatotroph tumors. Of these, seven patients are still receiving treatment, and six patients have terminated treatment. The reasons for discontinuation were poor efficacy (three patients), financial reasons (two patients), and patient preference (one patient). No patients required treatment discontinuation owing to adverse events. Furthermore, one case of a lactotroph tumor, which achieved remission with CAPTEM but was discontinued after three years for financial reasons, remains in remission on imaging and maintained normal PRL levels for 15 months after discontinuation. The most significant issue is off-label use. Concern exists that financial constraints may prevent future patients from using TMZ.