Radiotherapy with concurrent temozolomide for the management of extraneural metastases in pituitary carcinoma

Abstract

Background Pituitary carcinomas (PC) are uncommon neuroendocrine tumors, accounting for 0.1% of all pituitary tumors. The diagnosis of PC is based on the presence of metastases from a pituitary adenoma, and not by local invasion or pathological features alone. PC is typically resistant to therapy, with a median overall survival (OS) of only 31 months. There is no standard treatment for PC, but maximal safe resection and radiation are performed when possible. Encouraging preliminary data on the use of temozolomide (TMZ)-based therapy has been previously reported. Methods We report the response to therapy and safety of radiation with concurrent temozolomide (RT/TMZ) in 2 adult patients with heavily pretreated PC and extraneural metastases. Results Both patients had prior history of pituitary macroadenoma. At the time of diagnosis of PC, Ki-67% was 24.2% and 10%, with positive p53 staining in one case. Metastatic sites included lymph nodes, liver and bone. Case-1 received RT/TMZ to the tumor bed in the skull base and to the metastases in the cervical lymph nodes. Case-2 received RT/TMZ to recurrent tumor involving portacaval lymph nodes. Both patients achieved excellent long-term control of the sites of treated extraneural metastases, with no significant acute or delayed toxicity. Conclusions RT/TMZ was safely delivered and might provide sustained control of extraneural metastases in PC. Although this retrospective report has limitations, RT/TMZ can be considered as a therapeutic option for the management of extraneural metastases in PC.

European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas

“…The response rate was 76%, i.e., higher than that reported with TMZ alone. However, some of the patients had not received prior RT (11,125,126,127).…”

Treatment of aggressive pituitary tumours and carcinomas: results of a European Society of Endocrinology (ESE) survey 2016

“…Subsequent larger studies, still with limited number of patients: 13 (19), 24 (2), 31 (13) and 41 (14) patients have described lower response rates, about 45%, likely reflecting an early publication bias of patients with successful outcomes. In most cases, TMZ has been used as a single agent, others have used TMZ in combination with other drugs, such as capecitabine (20) or concurrent with radiotherapy (21,22,23), which is the standard treatment for glioblastomas (15). Whether such combinations result in an improved outcome in patients with APT, compared to monotherapy, has not been ascertained.…”

Pituitary carcinoma: The University of Texas MD Anderson Cancer Center experience

“…Our experience suggests that a multimodality approach involving a combination of surgical resection, radiotherapy and chemotherapy (particularly TMZ-based) correlates with better outcome (2-year OS rate 71%, 3-year OS rate 59%, 5-year OS rate 35%), compared with previous reports in the literature (Table 2). 1, 6, 7, 21…”

“…Further reports described the effective use of TMZ combined with capecitabine in recurrent and metastatic PNETs 11, 12, 21, 36-38 . The addition of capecitabine to TMZ (CAPTEM) is based on the theory that sequential pretreatment with capecitabine may potentiate the cytotoxicity of TMZ by synergistically depleting thymidine, leading to apoptosis.…”

“…Nevertheless, response to standard treatment is usually transient and PC recurrence is common, with a reported median overall survival (OS) of 1 year. 1, 6 Improved outcome has been recently reported with the use of chemotherapy in recurrent pituitary neuroendocrine tumors, 1, 7 especially temozolomide (TMZ) 8-18 as a single agent, in combination with capecitabine 19 or concurrently with radiotherapy 20, 21 . Recent practice guidelines for the management of aggressive pituitary tumors and PC have recommended temozolomide as first line chemotherapy.…”