How and when to use temozolomide to treat aggressive pituitary tumours

Abstract

Temozolomide is an oral chemotherapy used to treat aggressive pituitary tumours since 2006. It is inexpensive and well tolerated, the main side effects are fatigue, nausea and cytopenia. Overall the studies demonstrate approximately 70% response rate for temozolomide, if response is defined radiologically as complete, partial response or stable disease. Using the more stringent criteria of complete or partial response, the success rate is near 40%. Functioning tumours respond more frequently than non-functioning tumours. Tumours which are depleted of methyl guanine methyltransferase (MGMT), as assessed by immunohistochemistry, also are more likely to respond. Temozolomide has an established role in treating pituitary tumours which have demonstrated metastases or which are refractory and progressing, despite all conventional treatment (so-called salvage treatment). The challenge is to offer temozolomide earlier in the pathway if appropriate. Tumours which demonstrate aggressive clinical behaviour (defined as clinically relevant growth despite optimal treatment) should be considered for temozolomide. One common situation when this might occur is tumour progression after surgery and radiotherapy. It is unnecessary to wait until salvage treatment is required. Anticipated (but not yet demonstrated) aggressive behaviour can be regarded as a potential indication for temozolomide, but there is currently insufficient evidence to recommend this. Ideally a trial should assess this potential indication. Early treatment could be considered in selected cases when high levels of proliferation and invasion were demonstrated, causing significant clinical concern.

Characteristic of Tumor Regrowth After Gamma Knife Radiosurgery and Outcomes of Repeat Gamma Knife Radiosurgery in Nonfunctioning Pituitary Adenomas

“…Recently, an international survey of clinical practice (27) recommended temozolomide as first line chemotherapeutic treatment of aggressive pituitary tumors or pituitary carcinomas. As previous reported, 69% (28) of patients could obtain complete response, partial response or stable disease. The success rate of clear tumor volume reduction (complete response or partial response) was 42% (28).…”

“…As previous reported, 69% (28) of patients could obtain complete response, partial response or stable disease. The success rate of clear tumor volume reduction (complete response or partial response) was 42% (28). There was rare data about radiotherapy for aggressive pituitary adenomas.…”

Aggressive Cushing’s Disease: Molecular Pathology and Its Therapeutic Approach

“…However, some recent studies have suggested that early use of temozolomide in these patients could result in a better outcome ( 88 , 121 ). In this regard, high-grade tumors on MRI, such as invasiveness and increasing tumor size, and pathological findings, including high MIB1-labeling index, could be a sign of temozolomide initiation after surgery under RT ( 130 , 131 ). However, patients administered with temozolomide in the early stage are relatively rare.…”

“…Tumors resistant to TMZ chemotherapy have been shown in a certain number of refractory pituitary tumors ( 130 ). Thus, a predictive marker for resistance to temozolomide needs to be identified.…”

Case Report: Temozolomide Treatment of Refractory Prolactinoma Resistant to Dopamine Agonists

“…Obviously, the effect of TMZ treatment has a strong correlation with the expression of MGMT in glioma (24,25). Specifically, the lower the degree of MGMT expression, the better the tumor's response to TMZ treatment.…”