Temozolomide (Temodar®) and capecitabine (Xeloda®) treatment of an aggressive corticotroph pituitary tumor

Thearle, Marie S.; Freda, Pamela U.; Bruce, Jeffrey N.; Isaacson, Steven R.; Lee, Yoomi; Fine, Robert L.

doi:10.1007/s11102-009-0211-1

Cited by 61 publications

(59 citation statements)

References 31 publications

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“…For example, proton therapy (30), bevacizumab (31), mammalian target of rapamycin inhibitor (Everolimus) (32), TMZ, and pasireotide (33), and TMZ and capecitabine (34) have been reported. Additional clinical trials to assess optimal regimens are needed.…”

Section: Discussionmentioning

confidence: 99%

DNA Mismatch Repair Protein (MSH6) Correlated With the Responses of Atypical Pituitary Adenomas and Pituitary Carcinomas to Temozolomide: The National Cooperative Study by the Japan Society for Hypothalamic and Pituitary Tumors

Hirohata

Asano

Ogawa

et al. 2013

The Journal of Clinical Endocrinology &Amp; Metabolism

109

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Section: Discussionmentioning

confidence: 99%

DNA Mismatch Repair Protein (MSH6) Correlated With the Responses of Atypical Pituitary Adenomas and Pituitary Carcinomas to Temozolomide: The National Cooperative Study by the Japan Society for Hypothalamic and Pituitary Tumors

Hirohata

Asano

Ogawa

et al. 2013

The Journal of Clinical Endocrinology &Amp; Metabolism

109

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“…Did not tolerate addition of etoposide and cisplatin. Patient entered hospice and died 1 month later NS Thearle et al[50] …”

mentioning

confidence: 99%

Temozolomide for corticotroph pituitary adenomas refractory to standard therapy

et al. 2010

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To highlight the potential of temozolomide (TMZ) to induce rapid tumor regression in patients with aggressive corticotroph adenomas (CA) that are refractory to surgery and radiation therapy and to review use of TMZ in other pituitary tumors. We present a case of a 56-year-old male with a 3 cm CA treated with transphenoidal surgery (TSS) and conventional radiotherapy in the same year. His hypercortisolemia recurred 11 years later with rapid tumor growth (to 4.2 × 2.5 cm) and he underwent a second TSS with good resection. The tumor recurred 6 months later with ophthalmoplegia. Over 16 months he underwent an additional three surgeries (two TSS, one craniotomy) and repeated conventional radiotherapy. Ki67 staining index on surgical specimens was 5-6%. Temozolomide is an oral alkylating agent approved for glioblastoma multiforme treatment that has only recently shown promise in treating some pituitary tumors. In this patient TMZ was started at 150 mg/m²/day, titrated to 200 mg/m²/day, taken 5 days per month. The only significant side effect was moderate nausea. After 10 weeks, the tumor showed a remarkable 60% regression with objective improvement in ophthalmoplegia. Treatment of aggressive CAs represents a therapeutic challenge and in some cases surgical debulking and radiotherapy are of limited success. Few reports of CAs responsive to TMZ have been reported in the literature. To our knowledge, this case represents the most rapid robust CA shrinkage response reported to date. Further randomized clinical trials of TMZ in the treatment of aggressive pituitary adenomas are warranted.

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“…In addition, the minimum stably effective concentration of TMZ (250 µM) in this study is above that reasonably achievable clinically (100 µM) (32). This may help explain why some patients with invasive pituitary adenoma are resistant to TMZ alone (18) and rapidly respond to the combination chemotherapy regimen of TMZ and capecitabine (33). Meanwhile, some caution must be exercised in extrapolating these results to the in vivo situation.…”

Section: Discussionmentioning

confidence: 70%

Effect of temozolomide on cell viability in gonadotroph adenoma cell lines

Liu²,

Yao³

et al. 2011

Oncol Rep

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Abstract. Invasive pituitary adenomas are usually refractory to routine neurosurgery, radiosurgery or medications, and alternative therapies are needed. The effects of temozolomide (TMZ) on the inhibition of gonadotroph adenoma cell viability and hormone secretion were evaluated. Cell viability and IC 50 values were evaluated after αT3-1 cells were treated with TMZ (31.25-1000 µM) or vehicle for 0-72 h. Cell cycle changes and the extent of apoptosis were detected using flow cytometry, TUNEL and TEM. The molecular mechanism of TMZ action was investigated by the Caspase-Glo ® assay and immunoblotting. Gonadotropin secretion was assessed using an immunoassay system. TMZ dose-and time-dependently suppressed cell proliferation (P<0.01 vs. control, 250 µM, 24 h) and induced S-phase accumulation and G2/M-phase arrest (P<0.05 vs. control, 250 µM, 24 h). Early apoptotic cells increased following a 24-h TMZ incubation (P<0.001 vs. control, 250 µM), consistent with TEM and TUNEL detection that exhibited morphological features of apoptosis. TMZ (250 µM) increased the level of caspase-3/7 by 6-fold, caspase-9 by 7-fold and caspase-8 by 3-fold after a 24-h incubation, while it attenuated Bcl-2 expression (P<0.001 vs.control) and raised the proteolysis of PARP. Both FSH and LH levels were significantly decreased by TMZ (P<0.01 vs. control, 250 µM, 24 h). TMZ inhibited cell proliferation and hormone secretion, and induced cell cycle arrest and apoptotic cell death in gonadotroph adenoma cells via both death receptor and mitochondrial pathways, suggesting that it may represent a useful medical management strategy of invasive gonadotroph adenomas.

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Temozolomide (Temodar®) and capecitabine (Xeloda®) treatment of an aggressive corticotroph pituitary tumor

Cited by 61 publications

References 31 publications

DNA Mismatch Repair Protein (MSH6) Correlated With the Responses of Atypical Pituitary Adenomas and Pituitary Carcinomas to Temozolomide: The National Cooperative Study by the Japan Society for Hypothalamic and Pituitary Tumors

DNA Mismatch Repair Protein (MSH6) Correlated With the Responses of Atypical Pituitary Adenomas and Pituitary Carcinomas to Temozolomide: The National Cooperative Study by the Japan Society for Hypothalamic and Pituitary Tumors

Temozolomide for corticotroph pituitary adenomas refractory to standard therapy

Effect of temozolomide on cell viability in gonadotroph adenoma cell lines

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