Phase II Study of Temozolomide and Thalidomide in Patients With Metastatic Neuroendocrine Tumors

Kulke, Matthew H.; Stuart, Keith; Enzinger, Peter C.; Ryan, David P.; Clark, Jeffrey W.; Muzikansky, Alona; Vincitore, Michele; Michelini, Ann; Fuchs, Charles S.

doi:10.1200/jco.2005.03.6046

Cited by 473 publications

(274 citation statements)

References 20 publications

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“…Recent clinical trials have demonstrated that patients with pancreatic neuroendocrine tumors more often benefit from temozolimide-based therapies compared with neuroendocrine tumors from non-pancreatic sites of origin. 26,27 Thus, an immunohistochemical marker that can reliably determine the primary site of origin for a metastatic neuroendocrine tumor would have tremendous diagnostic utility. …”

Section: Discussionmentioning

confidence: 99%

PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from ileal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma

et al. 2011

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PAX (paired box) genes encode a family of transcription factors that regulate organogenesis in a variety of organs. Very little is known about the role of PAX8 in endocrine cell development and the expression of PAX8 in neuroendocrine tumors. The purpose of this study was to analyze PAX8 immunohistochemical expression in gastroenteropancreatic and pulmonary well-differentiated neuroendocrine tumors to determine whether PAX8 can reliably distinguish pancreatic neuroendocrine tumors from neuroendocrine tumors of other anatomic sites and other pancreatic non-ductal neoplasms. In total, 221 well-differentiated neuroendocrine tumors were evaluated: 174 primary neuroendocrine tumors (66 pancreatic, 31 ileal, 21 pulmonary, 20 gastric, 17 rectal, 11 appendiceal, and 8 duodenal) and 47 neuroendocrine tumors metastatic to the liver (31 pancreatic, 11 ileal, 2 pulmonary, 2 duodenal, and 1 rectal). Fifteen solid-pseudopapillary neoplasms and six acinar cell carcinomas of the pancreas were also evaluated. PAX8 was positive in 49/66 (74%) primary pancreatic neuroendocrine tumors. PAX8 expression did not correlate with World Health Organization categorization, grade, size, functional status, or the presence of liver or lymph node metastasis. PAX8 expression was identified in 0/31 (0%) ileal, 0/21 (0%) pulmonary, 2/20 (10%) gastric, 5/17 (29%) rectal, 1/11 (9%) appendiceal, and 6/8 (75%) duodenal neuroendocrine tumors. PAX8 was positive in 4/15 (27%) solid-pseudopapillary neoplasms of the pancreas, whereas all acinar cell carcinomas (0/6) lacked immunoreactivity. Among liver metastases, only pancreatic neuroendocrine tumors (20/31, 65%) were PAX8 positive, whereas no cases of ileal (0/11), pulmonary (0/2), duodenal (0/2), and rectal (0/1) neuroendocrine tumor metastases were PAX8 positive. PAX8 is expressed in primary and metastatic pancreatic well-differentiated neuroendocrine tumors, and its expression can reliably distinguish pancreatic from ileal and pulmonary well-differentiated neuroendocrine tumors. Duodenal neuroendocrine tumors and a subset of rectal, gastric, and appendiceal neuroendocrine tumors may also express PAX8. PAX8 expression can distinguish pancreatic neuroendocrine tumors from acinar cell carcinomas, but its utility in distinguishing neuroendocrine tumors from solid-pseudopapillary neoplasms is limited.

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Section: Discussionmentioning

confidence: 99%

PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from ileal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma

et al. 2011

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“…17 Temozolomide is accepted as an essential component of adjuvant therapy in the treatment of glioblastoma multiforme and other tumors of the central nervous system. [30][31][32] Recent reports indicate its efficacy in advancedstage, malignant neuroendocrine neoplasia 33,34 and in melanoma. 35 The standard therapeutic dose of temozolomide is 150 to 200 mg/m 2 daily for 5 of every 28 days.…”

Section: Temozolomidementioning

confidence: 99%

Treatment of pituitary neoplasms with temozolomide

Syro

Ortíz

Scheithauer

et al. 2010

Cancer

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Temozolomide, an orally administered alkylating agent, is used to treat malignant gliomas. Recent reports also have documented its efficacy in the treatment of pituitary adenomas and carcinomas. Temozolomide methylates DNA and thereby exhibits an antitumor effect. O 6 -methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme, removes alkylating adducts induced by temozolomide, counteracting its effects. The authors of this review conducted a Medline database search regarding temozolomide in the treatment of pituitary tumors. Demographic characteristics, tumor types, and therapeutic responses were noted in all patients. Data regarding MGMT immunoexpression, which was documented in some studies, were correlated with information regarding clinical and radiologic responses. To date, there have been 19 reported cases of adenohypophyseal tumors treated with temozolomide, including 13 adenomas and 6 carcinomas. Ten of those 13 adenomas responded favorably, and 2 nonresponsive tumors had highlevel MGMT immunoexpression. All 6 carcinomas responded to therapy, but data regarding MGMT expression were available for only 3 patients, and each had low MGMT expression. In 2 adenomas, morphologic studies were performed both before and after the patients received temozolomide. The responsive tumor had necrosis, hemorrhage, fibrosis, and neuronal differentiation. The nonresponsive tumor had no changes. There have been no reported complications attributable to temozolomide. The current results indicated that temozolomide is efficacious in the treatment of aggressive pituitary adenomas and pituitary carcinomas. Evidence indicated that low-level MGMT immunoexpression is correlated with a favorable response. A significant proportion of pituitary adenomas and carcinomas had low MGMT immunoexpression. Cancer 2011;117:454-62.

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“…Temozolomide (Table 3) [22][23][24][25][26][27][28][29] Temozolomide is an oral alkylating agent that is used to treat glioblastoma and melanoma. Because the side-effects of temozolomide are mild and it is an oral drug, temozolomide chemotherapy is expected to be less stressful for patients, and several studies of combination therapies with other drugs have been conducted in addition to a study of temozolomide alone.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic chemotherapy for pancreatic neuroendocrine tumors

Okusaka¹,

Ueno²,

Morizane³

et al. 2015

J Hepato Biliary Pancreat

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Advanced neuroendocrine tumors are incurable, and most patients will succumb to the disease. Chemotherapies with cytotoxic agents such as streptozocin, 5-fluorouracil, or temozolomide have been frequently used as drug therapies for neuroendocrine tumors. Streptozocin, which is the only approved cytotoxic agent available for the treatment of this disease in many countries, has been considered a key agent for the treatment of advanced neuroendocrine tumors based on the results of phase III studies. However, the widespread acceptance of streptozocin-based chemotherapy for this indication has been limited by concerns regarding toxicity. Recent prospective and retrospective studies showed the promising activity of a temozolomide-based regimen, although an adequate prospective controlled study defining the role of temozolomide in the treatment of neuroendocrine tumors is lacking. The promising activity of cytotoxic agents awaits confirmation; solid evidence-based recommendations and treatment decisions are needed for the optimal use of chemotherapy against this disease.

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Phase II Study of Temozolomide and Thalidomide in Patients With Metastatic Neuroendocrine Tumors

Abstract: Orally administered temozolomide and thalidomide seems to be an active regimen for the treatment of neuroendocrine tumors. In this 29-patient study, this regimen appeared more active in pancreatic endocrine tumors than in carcinoid tumors.

Cited by 473 publications

References 20 publications

PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from ileal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma

PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from ileal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma

Treatment of pituitary neoplasms with temozolomide

Cytotoxic chemotherapy for pancreatic neuroendocrine tumors

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