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Background: Metastatic neuroendocrine tumors of the thymus are exceedingly rare with an annual incidence of approximately 0.2 per 1,000,000. They are highly resistant to therapy and there have been no reports of an objective radiographic response to treatment., Materials and Methods: The authors retrospectively evaluated 3 patients with progressive, metastatic neuroendocrine tumors of the thymus who were treated with a combination of capecitabine and temozolomide. Radiographic scans were evaluated and response assessed using RECIST criteria., Results: One patient experienced a partial radiographic response, another patient experienced a minor response and the third patient experienced stable disease as the best response to treatment., Conclusion: The combination of capecitabine and temozolomide appears to be active in a rare neuroendocrine malignancy that is generally refractory to systemic therapy. Prospective multicenter trials are needed to validate this strategy., (Copyright © 2013 S. Karger AG, Basel.)

Background: Gastrointestinal neuroendocrine tumors (NETs) are heterogeneous neoplasms that vary in mortality according to location of primary tumor and stage of disease. Past analyses of survival suggest a trend towards improving longevity among patients with metastatic mid-gut NETs., Methods: We evaluated all cases of metastatic NETs of the mid-gut seen in our institution between 1999 and 2003, measuring survival from time of diagnosis of distant metastatic disease. Median and 5-year survival rates were estimated using Kaplan-Meier methodology. We assessed the impact of various prognostic factors including age, gender, hepatic cytoreductive surgery, and operative resection of the primary tumor., Results: 146 cases of metastatic mid-gut NETs were identified. The median overall survival was 103 months and the 5-year survival rate was 75%. Most patients (91%) received octreotide therapy. Other medical treatments included hepatic artery embolization, chemotherapy, and peptide receptor radiotherapy. Primary tumor resection was performed in 69% of cases, and hepatic cytoreductive surgery in 22% of cases. A median survival of 95 months was observed among patients who did not undergo cytoreductive surgery. Operative resection of the primary tumor was not associated with a significant survival advantage., Conclusions: Median overall survival is 103 months (8.5 years) in patients with metastatic mid-gut NETs. Among patients who are not candidates for hepatic cytoreductive surgery, median survival is 95 months (7.9 years). Resection of the primary tumor does not appear to be associated with a survival benefit in the metastatic setting., (Copyright 2009 S. Karger AG, Basel.)

Background/aims: The use of chemoradiation in the management of locally advanced pancreatic endocrine tumors has not been reported in the medical literature. Patients with unresectable tumors are often included in trials of systemic chemotherapy, and use of external beam radiation has been only described in few case reports. Given the sensitivity of pancreatic endocrine tumors to cytotoxic agents including streptozocin, doxorubicin and 5-FU, we have hypothesized that the combination of concurrent and sequential chemotherapy and radiation will yield higher response rates than acheivable with chemotherapy alone., Methods: Six patients with locally advanced pancreatic endocrine tumors were treated with a protocol consisting of radiation concurrent with infusional 5-FU (or capecitabine) along with induction and consolidation chemotherapy (streptozocin and doxorubicin). We retrospectively determined the objective radiographic response rate., Results: The objective response rate was 80%. With a median follow-up of 29 months, all six patients in the study have had continued reduction in tumor size from the time of the first posttreatment scan to the most recent scan. None of the patients have experienced local or metastatic disease progression. Treatment was well tolerated with minimal toxicity., Conclusion: The combination of concurrent and sequential chemoradiotherapy appears to be a highly effective treatment for locally advanced pancreatic endocrine tumors., (Copyright 2007 S. Karger AG, Basel.)

OctreoTher ((90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide, a.k.a. (90)Y-SMT 487) consists of a somatostatin peptide analogue (Tyr(3)-octreotide), coupled with a complexing moiety (DOTA), and labeled with a tightly bound beta-emitter (yttrium-90). By targeting somatostatin receptor-positive tumors (as imaged by OctreaScan it may deliver a tumoricidal dose of radiation. Phase I clinical trials, conducted in patients with neuroendocrine tumors, established the safety and tolerability of the dose selected for further study and demonstrated the capacity of OctreoTher to deliver radiation doses to tumors that resulted in significant neuroendocrine tumor shrinkage. Novartis-sponsored phase II studies will soon begin to test the efficacy of OctreoTher in breast and small cell lung cancer. A fixed-dose regimen of 120 mCi/cycle x 3 cycles administered with concomitant amino acid infusion has been chosen for the study. Phase I data and published literature support that this fixed dose regimen will be safely tolerated., (Copyright 2000 S. Karger AG, Basel)

Somatostatin receptors (SS-R) have been identified in membrane homogenates or tissue sections from several hundred human tumors. SS-R have been found in most neuroendocrine tumors, i.e. GH- and TSH-producing pituitary tumors, endocrine gastroenteropancreatic (GEP) tumors, paragangliomas, pheochromocytomas, medullary thyroid carcinomas (MTC) and small cell lung carcinomas. SS-R have also been found in the majority of malignant lymphomas, in several brain tumors (all meningiomas, most astrocytomas) and in breast tumors. The majority of tumors expressing SS-R are rather differentiated, e.g. astrocytomas in contrast to glioblastomas, but exceptions exist such as high grade malignant lymphomas. An inverse relationship exists between SS-R and receptors for epidermal growth factor in lung tumors, glial tumors and most breast tumors, whereas meningiomas express both receptors simultaneously. A minority of tumors such as ovarian tumors, MTC and insulinomas, express a subtype of SS-R, characterized by low affinity for the octapeptide SS analog octreotide. The function of SS-R in human tumors differs according to tumor type, SS-R in pituitary and GEP tumors mediate hormone secretion inhibition, and have possibly some antiproliferative effects. In meningiomas, however, activation of SS-R inhibits forskolin-stimulated adenylate cyclase activity, and weakly stimulates proliferation. Although SS-R seem to mediate antiproliferative effects in animal models and cell lines of lymphomas, breast and lung tumors, such an effect has not yet been convincingly documented in human primary tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

In a phase I study, a monthly regimen of dianhydrogalactitol 60 mg/m2 X 1 day, VP-16-213 60 mg/m2 X 3 days, and cis-platinum 20 mg/m2 X 3 days produced clinically acceptable toxicity. The program is suitable for outpatient administration and may have a role in the management of selected patients with advanced cancer.