High Response Rates and Prolonged Survival in Patients With Corticotroph Pituitary Tumors and Refractory Cushing Disease From Capecitabine and Temozolomide (CAPTEM)

Zacharia, Brad E.; Gulati, Anthony P.; Bruce, Jeffrey N.; Carminucci, Arthur; Wardlaw, Sharon L.; Siegelin, Markus D.; Remotti, Helen; Lignelli, Angela; Fine, Robert L.

doi:10.1227/neu.0000000000000251

Cited by 82 publications

(51 citation statements)

References 32 publications

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“…In this patient, MGMT remained low. In other studies (25,105), MSH6, MLH1, MSH2 and PMS2 did not predict the effect of TMZ.…”

Section: -Dna Mismatch Repair (Mmr) Proteinsmentioning

confidence: 73%

“…A study using treatment with capecitabine before TMZ (CAPTEM) found a partial response of long duration in 4 out of 4 corticotroph tumours, of which one was a carcinoma (105). In studies with NET cell lines, the authors had observed a synergistic apoptosis when TMZ had been given after pretreatment with capecitabine compared with TMZ alone.…”

Section: Combination Of Tmz With Other Drugsmentioning

confidence: 99%

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

Raverot

Burman

McCormack

et al. 2018

European Journal of Endocrinology

477

583

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Background: Pituitary tumours are common and easily treated by surgery or medical treatment in most cases. However, a small subset of pituitary tumours does not respond to standard medical treatment and presents with multiple local recurrences (aggressive pituitary tumours) and in rare occasion with metastases (pituitary carcinoma). The present European Society of Endocrinology (ESE) guideline aims to provide clinical guidance on diagnosis, treatment and follow-up in aggressive pituitary tumours and carcinomas. Methods: We decided upfront, while acknowledging that literature on aggressive pituitary tumours and carcinomas is scarce, to systematically review the literature according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The review focused primarily on first-and second-line treatment in aggressive pituitary tumours and carcinomas. We included 14 single-arm cohort studies (total number of patients = 116) most on temozolomide treatment (n = 11 studies, total number of patients = 106). A positive treatment effect was seen in 47% (95% CI: 36-58%) of temozolomide treated. Data from the recently performed ESE survey on aggressive pituitary tumours and carcinomas (165 patients) were also used as backbone for the guideline. In patients responding to first-line temozolomide, we suggest continuing treatment for at least 6 months in total. Furthermore, the guideline offers recommendations for patients who recurred after temozolomide treatment, for those who did not respond to temozolomide and for patients with systemic metastasis.

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“…In this patient, MGMT remained low. In other studies (25,105), MSH6, MLH1, MSH2 and PMS2 did not predict the effect of TMZ.…”

Section: -Dna Mismatch Repair (Mmr) Proteinsmentioning

confidence: 73%

Section: Combination Of Tmz With Other Drugsmentioning

confidence: 99%

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

Raverot

Burman

McCormack

et al. 2018

European Journal of Endocrinology

477

583

View full text Add to dashboard Cite

show abstract

“…Approximately 20 corticotroph tumors have been treated with temozolomide in the literature, 3 of which were SCA carcinomas which did not maintain response to temozolomide [22,35,54]. One group reported use of a combined regimen of temozolomide and capecitabine in a patient with an SCA which did lead to a reduction in tumor size [65].…”

Section: Managementmentioning

confidence: 99%

Silent corticotroph adenomas

2018

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Purpose-Silent corticotroph adenomas (SCAs) comprise 20% of all corticotroph adenomas and 3-19% of nonfunctioning adenomas (NFAs). As they do not manifest clinical or biochemical hypercortisolism, they are diagnosed after pathologic examination of resected tumor tissue demonstrates positive ACTH expression. While preoperative features are similar to those of NFAs, SCAs may have more cavernous sinus invasion. Further, patients with SCAs tend to have more frequent and earlier recurrences than those with NFAs, often necessitating multiple surgeries and other modalities of treatment. This article reviews the incidence, pathogenesis, and clinical behavior of SCAs.Methods-A systematic literature review was performed using PubMed for information regarding silent corticotroph adenomas.Results-Up to date findings regarding epidemiology, pathogenesis, pathology, clinical presentation, postoperative course, and management of patients with SCAs are presented.Conclusions-This review highlights the necessity of rigorous monitoring for recurrences and hypopituitarism in patients with SCAs.

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“…Increased risk of secondary malignancies (particularly leukemia and lymphoma) has been reported with prolonged administration of alkylating agents such as TMZ. It is currently unclear which regimen offers the best efficacy and which is associated with a reduced risk of secondary malignancy [121], whereas there are no data to support whether TMZ can be used alone or in combination with other medications such as pasireotide or capecitabine [122,123,124]. …”

Section: Treatmentmentioning

confidence: 99%

Aggressive Pituitary Tumors

et al. 2015

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Pituitary adenomas are common intracranial tumors that are mainly considered as benign. Rarely, these tumors can exhibit an aggressive behavior, characterized by gross invasion of the surrounding tissues, resistance to conventional treatment leading to early and frequent recurrences. Even more rarely, pituitary tumors can give rise to cerebrospinal or systemic metastases qualifying as pituitary carcinomas according to the latest WHO definition. In the same classification, a subset of tumors with relatively distinct histopathological features was identified and defined as atypical adenomas designated to follow a more aggressive clinical course. This classification, although clinically useful, does not provide an accurate correlation between histopathological findings and the clinical behavior of these tumors, neither is it adequate to convey the precise features of ‘aggressive' tumors. Thus, ‘aggressive' pituitary adenomas need to be properly defined with clinical, radiological, histological and molecular markers in order to identify patients at increased risk of early recurrence or subsequent tumor progression. At present, no single marker or classification system of pituitary tumor aggressiveness exists, and clinically useful information in the literature is insufficient to guide diagnostic and therapeutic decisions. Treatment of patients with aggressive pituitary tumors is challenging since conventional treatments often fail, necessitating multiple surgical procedures with additional radiotherapy. Although traditional chemotherapy applied in other neuroendocrine tumors has not been shown to be efficacious, newer agents, particularly temozolomide, have shown promising results and are currently used despite the lack of data from a randomized prospective trial. Molecular targeted therapies such as mTOR and epidermal growth factor inhibitors have also been applied and might prove to be useful in the management of these patients. In the present review, we provide information regarding the epidemiology and clinical, histopathological and molecular features of aggressive pituitary tumors using recent employed definitions. In addition, we review currently employed therapeutic means providing a therapeutic algorithm and highlight the need to identify more specific disease-related and prognostic markers and the necessity for central registration of these tumors.

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High Response Rates and Prolonged Survival in Patients With Corticotroph Pituitary Tumors and Refractory Cushing Disease From Capecitabine and Temozolomide (CAPTEM)

Abstract: This is the first report of prolonged antitumor response to and radiographic complete remissions as a result of CAPTEM in patients with aggressive pituitary tumors who had exhausted all other therapies.

Cited by 82 publications

References 32 publications

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

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

Silent corticotroph adenomas

Aggressive Pituitary Tumors

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