Cox proportional hazard analysis of sunitinib (SU) efficacy across subgroups of patients (pts) with progressive pancreatic neuroendocrine tumors (NET).

Raymond, Éric; Niccoli, Patricia; Raoul, Jean-Luc; Bang, Yeonghak; Borbath, Ivan; Lombard‐Bohas, Catherine; Valle, J. W.; Patyna, Shem; Chao, Richard C.; Donghui, LU

doi:10.1200/jco.2010.28.15_suppl.4031

Cited by 9 publications

(3 citation statements)

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“…Patients treated with sunitinib also showed a signifi cant delay in time to deterioration in emotional and physical functioning [92]. Moreover, sunitinib resulted in a clinically meaningful improvement in PFS across all subgroups studied, including number of prior treatments and previous or concomitant use of somatostatin analogues [93].…”

Section: Sunitinib In Gep-netsmentioning

confidence: 98%

Advances in the therapy of gastroenteropancreatic-neuroendocrine tumours (GEP-NETs)

et al. 2010

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Neuroendocrine tumours (NET) of the digestive tract comprise a broad range of malignancies. The therapeutic approach to these tumours has not evolved as it did in other tumour types in the last two decades. The deeper knowledge of the underlying molecular biology behind the growth of neuroendocrine cells has brought much information to light. We now know that somatostatin analogues may not only be considered as symptomatic treatment but also as antitumour agents. Sunitinib, a tyrosine kinase (TK) inhibitor with antiangiogenic and antitumoural properties, has been shown to induce significant improvement in progression-free survival in a randomised trial conducted in well-differentiated pancreatic islet-cell NETs. The relevance of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway seems to be crucial in gastroenteropancreatic (GEP)-NETs. In fact, mTOR inhibitors have shown activity in uncontrolled trials, and large, randomised trial results will be available shortly. In this article, we summarise the most recent available data on medical therapy for GEPNETs.

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Section: Sunitinib In Gep-netsmentioning

confidence: 98%

Advances in the therapy of gastroenteropancreatic-neuroendocrine tumours (GEP-NETs)

et al. 2010

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“…Everolimus and sunitinib have been the first novel-targeted agents to demonstrate significant clinical benefit in a randomized fashion in these tumors and we have incorporated them in our daily clinical armamentarium [6][7][8]. Moreover, other targeted agents like bevacizumab, pazopanib, and sorafenib are under clinical investigation and will hopefully be effective in extending the survival of patients with advanced GEP-NETs.…”

Section: Future Approaches: Realistic or Illusionmentioning

confidence: 99%

“…Moreover, several molecular-targeted agents like everolimus, sunitinib, temsirolimus, bevacizumab, sorafenib, or pazopanib among others have demonstrated clinical activity not only in GEP-NETs but also against other endocrine-derived tumors such as thyroid cancer [6][7][8][9][10][11][12][13][14][15]. We are changing the natural history of GEP-NETs by increasing overall survival with new targeted agents.…”

Section: Introductionmentioning

confidence: 99%

Gastroenteropancreatic neuroendocrine tumor cancer stem cells: do they exist?

Grande

Capdevila

Barriuso

et al. 2011

Cancer Metastasis Rev

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Neuroendocrine tumors (NETs) comprise a broad range of neoplasms that share biological and embryological origin. A deeper knowledge in the underlying molecular biology that results in the development and spread of NETs has allowed the use of novel-targeted therapies against angiogenesis and intracellular pathways, key checkpoints that govern growth, and proliferation of these tumors. Unfortunately, the possibility of cure is still far for patients with advanced stages. Cancer stem cells (CSCs) are present in most solid tumors. Nevertheless, there is limited evidence for the presence of CSCs in NETs. In this review, we will discuss the embryonic origin and possible existence of a gastroenteropancreatic neuroendocrine cancer stem cell. Here, we summarize the body of evidence supporting the presence of active embryological pathways like Notch, Wnt-β-catenin, Hedgehog, or transforming growth factor-β in NETs. New therapeutic approaches in the field of CSCs seem to have a clear role in the treatment of medulloblastomas and basal cell carcinomas, but their future value in other solid tumor types including NETs remains unclear.

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A phase I study of bevacizumab (B) in combination with everolimus (E) and erlotinib (E) in advanced cancer (BEE)

Bullock

Petros

Younis

et al. 2010

Cancer Chemother Pharmacol

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Purpose-VEGF, mTOR, and EGFR inhibitors have demonstrated anti-tumor and antiangiogenic effects alone and in combination with each other. This study evaluated the safety, tolerability, and pharmacokinetics of bevacizumab, everolimus and erlotinib combination.Methods-Doublet therapy consisted of bevacizumab at 10mg/kg every 14 days and everolimus 5mg daily which escalated to 10mg daily. Erlotinib 75mg daily was added to the phase II dose recommended phase II dose (RPTD) of bevacizumab and everolimus. Dose limiting toxicity (DLT) was assessed in Cycle 1.Results-Forty-eight patients with advanced solid malignancies were evaluable for DLT and efficacy. No DLTs were observed in the doublet dose escalation. Two DLTs (grade 3 mucositis and grade 3 rash) were observed with the addition of erlotinib 75mg daily. Consequently, triplet doses were adjusted and were better tolerated. Four patients had a partial response. Median progression-free survival (PFS) for the doublet therapy was 6.0 months (0.5-32+ months) and 5.5 months (0.8-27+ months) for the triplet therapy. Systemic exposure of everolimus was significantly higher in combination with erlotinib (476 ± 161 ng*hr/mL) compared to when given alone (393 ± 156 ng*hr/mL; p = 0.020).Conclusions-The RPTD for the doublet therapy is bevacizumab 10 mg/kg every 14 days and everolimus 10 mg daily, and the RPTD for the triplet therapy is bevacizumab 5mg/kg every 14 days, everolimus 5mg and erlotinib 75mg daily. Prolonged disease stability was demonstrated in tumors known to respond to mTOR inhibition and potentially resistant to VEGF blockade.

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Cox proportional hazard analysis of sunitinib (SU) efficacy across subgroups of patients (pts) with progressive pancreatic neuroendocrine tumors (NET).

Cited by 9 publications

References 0 publications

Advances in the therapy of gastroenteropancreatic-neuroendocrine tumours (GEP-NETs)

Advances in the therapy of gastroenteropancreatic-neuroendocrine tumours (GEP-NETs)

Gastroenteropancreatic neuroendocrine tumor cancer stem cells: do they exist?

A phase I study of bevacizumab (B) in combination with everolimus (E) and erlotinib (E) in advanced cancer (BEE)

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