Capecitabine Plus Erlotinib in Gemcitabine-Refractory Advanced Pancreatic Cancer

Kulke, Matthew H.; Blaszkowsky, Lawrence S.; Ryan, David P.; Clark, Jeffrey W.; Meyerhardt, Jeffrey A.; Zhu, Andrew X.; Enzinger, Peter C.; Kwak, Eunice L.; Muzikansky, Alona; Lawrence, Colleen; Fuchs, Charles S.

doi:10.1200/jco.2007.11.8521

Cited by 158 publications

(92 citation statements)

References 38 publications

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“…Gemcitabine plus oxaliplatin (GEMOX), oxaliplatin plus capecitabine (XELOX), capecitabine plus erlotinib, docetaxel plus gefitinib, and FOLFOX have been tested in gemcitabine-refractory pancreatic cancer patients and showed disease control rates of 19 -53% and a median OS range of 2.9 -6.7 months (Tsavaris et al, 2005;Demols et al, 2006;Kulke et al, 2007;Xiong et al, 2008;Brell et al, 2009;Novarino et al, 2009). Recently, another oxaliplatinbased regimen, 5-FU/FA plus oxaliplatin (OFF), was shown to offer significantly improved survival compared with 5-FU/FA (FF) in a phase III trial (CONKO 003) (Pelzer et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…To date, few studies have assessed second-line chemotherapy, primarily because of poor prognosis (Nakachi et al, 2007) and because of the limited life expectancy of those with advanced pancreatic cancer after failure of first-line chemotherapy (Kozuch et al, 2001;Tsavaris et al, 2005;Kulke et al, 2007;Xiong et al, 2008;Novarino et al, 2009). There is, therefore, a growing unmet need for a second-line chemotherapy regimen to treat patients with gemcitabine-refractory pancreatic cancer (Boeck and Heinemann, 2008;Kang and Saif, 2008).…”

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confidence: 99%

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A randomised phase II study of modified FOLFIRI.3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer

et al. 2009

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BACKGROUND: Only a few clinical trials have been conducted in patients with advanced pancreatic cancer after failure of first-line gemcitabine-based chemotherapy. Therefore, there is no current consensus on the treatment of these patients. We conducted a randomised phase II study of the modified FOLFIRI.3 (mFOLFIRI.3; a regimen combining 5-fluorouracil (5-FU), folinic acid, and irinotecan) and modified FOLFOX (mFOLFOX; a regimen combining folinic acid, 5-FU, and oxaliplatin) regimens as second-line treatments in patients with gemcitabine-refractory pancreatic cancer. METHODS: The primary end point was the 6-month overall survival rate. The mFOlFIRI.3 regimen consisted of irinotecan (70 mg m À2 ; days 1 and 3), leucovorin (400 mg m À2 ; day 1), and 5-FU (2000 mg m À2 ; days 1 and 2) every 2 weeks. The mFOLFOX regimen was composed of oxaliplatin (85 mg m À2 ; day 1), leucovorin (400 mg m À2 ; day 1), and 5-FU (2000 mg m À2 ; days 1 and 2) every 2 weeks. RESULTS: Sixty-one patients were randomised to mFOLFIRI.3 (n ¼ 31) or mFOLFOX (n ¼ 30) regimen. The six-month survival rates were 27% (95% confidence interval (CI) ¼ 13 -46%) and 30% (95% CI ¼ 15 -49%), respectively. The median overall survival periods were 16.6 and 14.9 weeks, respectively. Disease control was achieved in 23% (95% CI ¼ 10 -42%) and 17% patients (95% CI ¼ 6 -35%), respectively. The number of patients with at least one grade 3/4 toxicity was identical (11 patients, 38%) in both groups: neutropenia (7 patients under mFOLFIRI.3 regimen vs 6 patients under mFOLFOX regimen), asthaenia (1 vs 4), vomiting (3 in both), diarrhoea (2 vs 0), and mucositis (1 vs 2). CONCLUSION: Both mFOLFIRI.3 and mFOLFOX regimens were tolerated with manageable toxicity, offering modest activities as second-line treatments for patients with advanced pancreatic cancer, previously treated with gemcitabine.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

A randomised phase II study of modified FOLFIRI.3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer

et al. 2009

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“…Certain data are in favor of second-line therapy (12), whereas others do not encourage its use (13). Based on phase II data, a median survival of 4-6 months after the initiation of second-line treatment may be achieved with salvage chemotherapy in selected patients (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Use of gemcitabine as a second-line treatment following chemotherapy with folfirinox for metastatic pancreatic adenocarcinoma

et al. 2017

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Abstract. There is a lack of prospective data about second-line treatments for metastatic pancreatic ductal adenocarcinoma patients. This is partially due to recent changes in first-line chemotherapy treatments. Despite this dearth of information, 50.0% of the patients who experience failure with first-line folinic acid, 5-fluorouracil, irinotecan and oxaliplatin (folfirinox) treatment are eligible for additional chemotherapy.

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“…Despite improved multimodal therapeutic regimens, its prognosis has improved only marginally, resulting in a total 5-year survival rate, which is still as low as 5% (1). More recently, agents targeted against molecular determinants of cancer cells or tumor vessels, or both, have been tested successfully in clinical trials to expand the therapeutic spectrum (2)(3)(4). However, to take full advantage of targeted therapies, it is essential to achieve a more profound knowledge of the molecular determinants of tumor development and progression.…”

Section: Introductionmentioning

confidence: 99%

EFEMP1 Expression Promotes In vivo Tumor Growth in Human Pancreatic Adenocarcinoma

Seeliger¹,

Čamaj²,

Ischenko³

et al. 2009

Molecular Cancer Research

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The progression of pancreatic cancer is dependent on local tumor growth, angiogenesis, and metastasis. EFEMP1, a recently discovered member of the fibulin family, was characterized with regard to these key elements of pancreatic cancer progression. Differential gene expression was assessed by mRNA microarray hybridization in FG human pancreatic adenocarcinoma cells and L3.6pl cells, a highly metastatic variant of FG. In vivo orthotopic tumor growth of EFEMP1-transfected FG cells was examined in nude mice. To assess the angiogenic properties of EFEMP1, vascular endothelial growth factor (VEGF) production of tumor cells, endothelial cell proliferation and migration, and tumor microvessel density were analyzed in response to EFEMP1. Further, tumor cell apoptosis, cell cycle progression, and resistance to cytotoxic agents were quantitated by propidium iodide staining and flow cytometry. In microarray hybridization, EFEMP1 was shown to be significantly up-regulated in L3.6pl cells compared with FG cells. Concordantly, EFEMP1 transfection of FG cells stimulated orthotopic and metastatic tumor growth in vivo. EFEMP1 expression resulted in a stimulation of VEGF production by tumor cells and an increased number of CD31-positive microvessels. Endothelial cell proliferation and migration were not altered by EFEMP1, indicating an indirect angiogenic effect. Further, EFEMP1 expression decreased apoptosis and promoted cell cycle progression in response to serum starvation or exposure to gemcitabine, 5-fluorouracil, and irinotecan. EFEMP1 has protumorigenic effects on pancreatic cancer in vivo and in vitro mediated by VEGF-driven angiogenesis and antiapoptotic mechanisms. Hence, EFEMP1 is a promising candidate for assessing prognosis and individualizing therapy in a clinical tumor setting. (Mol Cancer Res 2009;7(2):189-98)

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Capecitabine Plus Erlotinib in Gemcitabine-Refractory Advanced Pancreatic Cancer

Cited by 158 publications

References 38 publications

A randomised phase II study of modified FOLFIRI.3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer

A randomised phase II study of modified FOLFIRI.3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer

Use of gemcitabine as a second-line treatment following chemotherapy with folfirinox for metastatic pancreatic adenocarcinoma

EFEMP1 Expression Promotes In vivo Tumor Growth in Human Pancreatic Adenocarcinoma

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