Temozolomide therapy for aggressive pituitary tumours – current understanding and future perspectives

“…In patients failing surgery and radiation with ongoing tumor progression or detection of metastases, the 2018 ESE guidelines suggest systemic therapy with temozolomide as first-line chemotherapy. Temozolomide is an alkylating chemotherapeutic drug characterized by almost 100 % bioavailability after oral administration, and a good penetrance into the central nervous system [10]. It is usually applied with a dose of 150 − 200 mg/m 2 for 5 days every 28 days, starting with the lower dose and increasing in subsequent cycles depending on tolerability.…”

Section: Chemotherapy Temozolomidementioning

confidence: 99%

Medical Therapy of Aggressive Pituitary Tumors

Petersenn¹

2021

Exp Clin Endocrinol Diabetes

View full text Add to dashboard Cite

The rare aggressive pituitary adenoma presents a special challenge, due to the heterogenous presentation of the disease. The prognosis of aggressive pituitary adenomas has been improved due to recent studies demonstrating clinically-relevant efficacy of temozolomide, which is now considered first-line chemotherapy. However, there is limited data on second-line therapies in patients with treatment failure. This review presents a summary on the potential of medical therapies in aggressive pituitary tumors.

show abstract

“…Silencing through other mechanisms or genetic variants of MGMT may explain some of the discordances. (139,140). In pituitary tumours, the preferred method to measure MGMT should be by IHC (17,140).…”

Section: Is Mgmt Associated With the Response To Temozolomide?mentioning

confidence: 99%

“…Although MGMT seem to be a main determinant of TMZ effect, other mechanisms of resistance have been considered. Acquired resistance during treatment might occur due to drug-or radiotherapy-induced epigenetic changes or by selection of pre-existing resistant cell clones (139). Heterogeneous MGMT distribution in the tumour might result in an initial or partial response, i.e.…”

Section: Is Mgmt Associated With the Response To Temozolomide?mentioning

confidence: 99%

“…In our study 2/24 patients stopped TMZ after the first cycle due to side effects (hearing loss and urinary tract infection plus extreme fatigue respectively), which is in line with the ESE survey in which 11% of patients stopped TMZ due to side-effects (most frequently bone marrow suppression). Side-effects are otherwise mostly mild (fatigue and nausea/vomiting most common) and in responders tolerating TMZ a prolonged duration of > 12 months might be favourable in terms of survival (129,139,143,144). Discontinuation of TMZ followed by a second attempt is generally accompanied by a lesser response, (16,(128)(129)(130).…”

Section: What Is the Long-term Outcome After Tmz Treatment And What To Do If Tmz Fails?mentioning

confidence: 99%

See 1 more Smart Citation

Cushing’s disease and aggressive pituitary tumours : Aspects on epidemiology, treatment, and long-term follow-up

Bengtsson

2021

Linköping University Medical Dissertations

View full text Add to dashboard Cite

This thesis focuses on clinical and epidemiological aspects of aggressive pituitary tumours/carcinomas and Cushing's disease. Pituitary carcinomas account for only 0.1-0.2% of the tumours originating from the anterior pituitary gland and are defined solely by the event of distant metastases, whereas aggressive pituitary tumours are defined by their clinical behaviour of rapid/progressive growth despite optimal treatment with surgery, radiotherapy and medical agents. The prognosis for individuals with aggressive tumours/carcinomas has been poor with few treatment options. However, case reports indicated better outcomes after treatment with the alkylating agent temozolomide. In study I and III, we investigated 24 patients (16 aggressive tumours and 8 carcinomas) given treatment with temozolomide. We found an initial response rate (tumour regression ≥30%) in 10/21 evaluable patients, with complete regression in two carcinomas. Favourable response was associated with low tumour expression of the DNA repair protein MGMT; in responders median 9% (range 5-20%) vs non-responders median 93% (50-100%). Our results also indicated a longer survival in patients with low MGMT. Out of 11 patients with MGMT >10%, nine died with an estimated median survival of 26 months (95% CI 14-38), whereas only 1/6 patients with lower MGMT died from tumour progression during a follow-up of median 83 months (range 12-161).

show abstract

Temozolomide therapy for aggressive pituitary tumours – current understanding and future perspectives

Cited by 24 publications

References 98 publications

Case Report: A Case of Pituitary Carcinoma Treated With Sequential Dual Immunotherapy and Vascular Endothelial Growth Factor Inhibition Therapy

Case Report: A Case of Pituitary Carcinoma Treated With Sequential Dual Immunotherapy and Vascular Endothelial Growth Factor Inhibition Therapy

Medical Therapy of Aggressive Pituitary Tumors

Cushing’s disease and aggressive pituitary tumours : Aspects on epidemiology, treatment, and long-term follow-up

Contact Info

Product

Resources

About