Streptozocin–Doxorubicin, Streptozocin–Fluorouracil, or Chlorozotocin in the Treatment of Advanced Islet-Cell Carcinoma

Moertel, Charles G.; Lefkopoulo, Myrto; Lipsitz, Stuart R.; Hahn, Richard G.; Klaassen, David J.

doi:10.1056/nejm199202203260804

Cited by 860 publications

(447 citation statements)

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“…Somatostatin analogues have proven successful in ameliorating symptoms of the carcinoid syndrome but its benefit in survival is unclear (Saltz et al, 1993). Streptozocin and DTIC-based regimens have been tested with only modest activity and may also be associated with significant toxicity (Moertel and Hanley, 1979;Engstrom et al, 1984;Moertel et al, 1992;Bukowski et al, 1994;Rivera and Ajani, 1998;Cheng and Saltz, 1999;Ramanathan et al, 2001;McCollum et al, 2004;Sun et al, 2005). As conventional systemic approaches remain insufficient and highly toxic, there is an obvious need for novel therapies in this tumour population.…”

Section: Discussionmentioning

confidence: 99%

“…Conventional chemotherapy has not shown a significant activity in advanced NEC, except for islet cell carcinomas (ICC) where streptozocin-based combinations with either 5-fluorouracil or doxorubicin have produced partial remissions in 40 -60% of selected patients (Moertel et al, 1982;Moertel et al, 1992). However, carcinoid tumours (CT) seem to be quite chemo-resistant, with response rates of o10% and a median 5-year survival of 18% (Oberg, 2001).…”

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confidence: 99%

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A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas

et al. 2006

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Standard cytotoxic treatments for neuroendocrine tumours have been associated with limited activity and remarkable toxicity. A phase II study was designed to evaluate the efficacy, safety and pharmacodynamics of temsirolimus in patients with advanced neuroendocrine carcinoma (NEC). Thirty-seven patients with advanced progressive NEC received intravenous weekly doses of 25 mg of temsirolimus. Patients were evaluated for tumour response, time to progression (TTP), overall survival (OS) and adverse events (AE). Twenty-two archival specimens, as well as 13 paired tumour biopsies obtained pretreatment and after 2 weeks of temsirolimus were assessed for potential predictive and correlative markers. The intent-to-treat response rate was 5.6% (95% CI 0.6 -18.7%), median TTP 6 months and 1-year OS rate 71.5%. The most frequent drug-related AE of all grades as percentage of patients were: fatigue (78%), hyperglycaemia (69%) and rash/desquamation (64%). Temsirolimus effectively inhibited the phosphorylation of S6 (P ¼ 0.02). Higher baseline levels of pmTOR (phosphorylated mammalian target of rapamycin) (P ¼ 0.01) predicted for a better response. Increases in pAKT (P ¼ 0.041) and decreases in pmTOR (P ¼ 0.048) after treatment were associated with an increased TTP. Temsirolimus appears to have little activity and does not warrant further single-agent evaluation in advanced NEC. Pharmacodynamic analysis revealed effective mTOR pathway downregulation.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas

et al. 2006

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“…Streptozocin (Table 1) [1][2][3][4][5][6][7][8][9][10][11][12][13][14] Streptozocin is a nitrosourea alkylating agent that is known to be taken up into cells by the glucose transport protein GLUT2 and to cause cell damage. Because GLUT2 is strongly expressed in pancreatic beta cells, streptozocin has been widely used to create animal models of diabetes mellitus.…”

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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“…While chemotherapy remains frequently used in neuroendocrine tumors [1,2], sunitinib [3] and everolimus [4] have been more recently approved expanding treatment options for patients with advanced/metastatic pancreatic neuroendocrine tumors. Mixing standard options including surgery and chemotherapy with novel therapies has become a common challenge for physicians in charge of treatment for patients with neuroendocrine tumors.…”

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confidence: 99%