Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group

Moore, Malcolm J.; Goldstein, David; Hamm, John; Figer, Arié; Hecht, J. Randolph; Gallinger, Steven; Au, Heather-Jane; Murawa, P.; Walde, David; Wolff, Robert A.; Campos, Daniel; Lim, Robert; Ding, Keyue; Clark, Gary M.; Voskoglou-Nomikos, Theodora; Ptasynski, Mieke; Parulekar, Wendy R.

doi:10.1200/jco.2006.07.9525

Cited by 3,452 publications

(2,535 citation statements)

References 33 publications

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“…Recent advances in the clinical management of this disease, especially new chemotherapeautic reagents, such as gemcitabine (Burris et al, 1997), have improved patient outcome. In addition, recent progress in molecular cancer biology has led to the development of new molecular targeting therapies for pancreatic cancer; some of these new drugs, such as erlotinib, an epidermal growth factor receptor inhibitor (Moore et al, 2007), have already shown clinical benefits. However, the efficacy of these new therapies has not been sufficient enough, with only a few months' improvement in median survival time, and additional molecular targets are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells

et al. 2007

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Pancreatic cancer still remains one of the most lethal diseases and establishment of new therapy is needed. The purpose of this study is to find novel factors involved in pancreatic cancer progression by proteomic approach. We compared pre-and postoperative serum protein profiling obtained from pancreatic cancer patients who had curative pancreatectomy using surface-enhanced laser desorption ionization time-of-flight mass spectrometry. The peak intensity levels of both 6630 and 6420 Da were significantly higher in the preoperative serum than in the postoperative serum (Po0.002). Sequential amino acid analysis identified these proteins to be apolipoprotein C-1 (ApoC-1). The high level of ApoC-1 in preoperative serum significantly correlated with poor prognosis. Furthermore, ApoC-1 was abundantly expressed in pancreas neoplastic epithelium, and was detected in the culture medium of the pancreatic cancer cell line in vitro, which suggests that cancer cells secrete ApoC-1. Inhibition of ApoC-1 expression by short interfering RNA suppressed cell proliferation and induced apoptosis of pancreatic cancer cells. The specific expression of ApoC-1 and its role in preventing from spontaneous apoptosis in pancreatic cancer cells suggest that ApoC-1 contributes to the aggressiveness of pancreatic cancer and will be useful as a new therapeutic target.

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Section: Introductionmentioning

confidence: 99%

Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells

et al. 2007

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“…Both of which showed an improved efficacy with gemcitabine/capecitabine combination with the UK study showing statistically superior survival advantage over gemcitabine alone (P ¼ 0.026) . However, more recently, erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, plus gemcitabine has also been reported to improve survival over gemcitabine alone (Moore et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Gastrazole (JB95008), a novel CCK2/gastrin receptor antagonist, in the treatment of advanced pancreatic cancer: results from two randomised controlled trials

et al. 2006

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Gastrin has been shown to be a growth stimulant in pancreatic cancer cells. Gastrazole is a potent and selective gastrin receptor antagonist. Two randomised blinded trials were conducted to assess the effect of gastrazole in advanced pancreatic cancer. Patients with biopsy-proven, inoperable pancreatic carcinoma were recruited. Trial A compared protracted venous infusion (PVI) gastrazole with PVI placebo, whereas trial B compared PVI gastrazole with PVI fluorouracil (5-FU). Eighteen patients were randomised in trial A. Gastrazole produced significantly better survival compared to placebo (median 7.9 months vs 4.5 months; 1-year survival: 33 vs 11%, respectively; log rank P ¼ 0.02). No difference in toxicity was seen between gastrazole and placebo, except central venous catheter and pump complications. Ninety-eight patients were randomised in trial B. No significant survival difference was detected between gastrazole and 5-FU (median: 3.6 vs 4.2 months; 1-year survival: 13.2 vs 26.2%, respectively; log rank P ¼ 0.42). Toxicity of gastrazole was mild with significantly less diarrhoea (P ¼ 0.03), stomatitis (Po0.001) and hand -foot syndrome (Po0.001) compared to 5-FU. Quality of life (QoL) assessment showed similar QoL between gastrazole and 5-FU at baseline and no significant differences occurred with treatment either between arms or within arms. Compared to placebo, patients with advanced pancreatic cancer treated with gastrazole appeared to live longer, albeit in a very small trial and will require confirmation with large-scale randomised data. However, it did not produce survival advantage over PVI 5-FU. Lack of toxicity for gastrazole may allow its combination with cytotoxic drugs.

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“…Only erlotinib, an inhibitor of the epidermal growth factor receptor and recently (September 2013) Abraxane (paclitaxel albumin-bound nanoparticles) have been approved by the FDA in combination with gemcitabine due to the significant improvement in patient survival and delay in tumor growth [5][6][7]. Due to its rather hydrophilic character, gemcitabine is unable to passively diffuse across the plasma membrane but it is transported into the cell by either human equilibrative (hENT) or sodiumgradient nucleoside transporters.…”

Section: Introductionmentioning

confidence: 99%

Peptide-functionalized nanoparticles for selective targeting of pancreatic tumor

Valetti¹,

Maione

Mura

et al. 2014

Journal of Controlled Release

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Chemotherapy for pancreatic cancer is hampered by the tumor physio-pathological complexity. Here we show a targeted nanomedicine using a new ligand, the CKAAKN peptide, which had been identified by phage display, as an efficient homing device within the pancreatic pathological microenvironment. Taking advantage of the squalenoylation platform, the CKAAKN peptide was conjugated to squalene (SQCKAAKN) and then co-nanoprecitated with the squalenoyl prodrug of gemcitabine (SQdFdC) giving near monodisperse nanoparticles (NPs) for safe intravenous injection. By interacting with a novel target pathway, the Wnt-2, the CKAAKN functionalization enabled nanoparticles: (i) to specifically interact with both tumor cells and angiogenic vessels and (ii) to simultaneously promote pericyte coverage, thus leading to the normalization of the vasculature likely improving the tumor accessibility for the therapy. All together, this approach represents a unique targeted nanoparticle design with remarkable selectivity towards pancreatic cancer and multiple mechanism of action. Graphical abstract

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Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group

Abstract: To our knowledge, this randomized phase III trial is the first to demonstrate statistically significantly improved survival in advanced pancreatic cancer by adding any agent to gemcitabine. The recommended dose of erlotinib with gemcitabine for this indication is 100 mg/d.

Cited by 3,452 publications

References 33 publications

Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells

Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells

Gastrazole (JB95008), a novel CCK2/gastrin receptor antagonist, in the treatment of advanced pancreatic cancer: results from two randomised controlled trials

Peptide-functionalized nanoparticles for selective targeting of pancreatic tumor

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