Metastatic Pancreatic Cancer 2008: Is the Glass Less Empty?

Nieto, Jacqueline; Grossbard, Michael L.; Kozuch, Peter

doi:10.1634/theoncologist.2007-0181erratum

Cited by 16 publications

(19 citation statements)

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“…It is the fifth leading cause of cancer-related death in Japan and the fourth in the United States, accounting for an estimated Ͼ23,000 deaths per year in Japan and Ͼ33,000 in the United States (2,3). Because the majority of patients have distant metastases even at their first presentation (4,5), the main therapeutic modality for pancreatic cancer is systemic chemotherapy, and gemcitabine monotherapy is the current standard (6). Gemcitabine treatment has significantly improved the median survival time of patients with advanced pancreatic cancer (7).…”

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confidence: 99%

Survival Prediction for Pancreatic Cancer Patients Receiving Gemcitabine Treatment

Matsubara

Ono

Honda

et al. 2010

Molecular & Cellular Proteomics

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Although gemcitabine monotherapy is the standard treatment for advanced pancreatic cancer, patient outcome varies significantly, and a considerable number do not benefit adequately. We therefore searched for new biomarkers predictive of overall patient survival. Using LC-MS, we compared the base-line plasma proteome between 29 representative patients with advanced pancreatic cancer who died within 100 days and 31 patients who survived for more than 400 days after receiving at least two cycles of the same gemcitabine monotherapy. Identified biomarker candidates were then challenged in a larger cohort of 304 patients treated with the same protocol using reverse-phase protein microarray. Among a total of 45,277 peptide peaks, we identified 637 peaks whose intensities differed significantly between the two groups (p < 0.001, Welch's t test). Two MS peaks with the highest statistical significance (p ‫؍‬ 2.6 ؋ 10 ؊4 and p ‫؍‬ 5.0 ؋ 10 ؊4) were revealed to be derived from ␣ 1 -antitrypsin and ␣ 1 -antichymotrypsin, respectively. The levels of ␣ 1 -antitrypsin (p ‫؍‬ 8.9 ؋ 10 ؊8) and ␣ 1 -antichymotrypsin (p ‫؍‬ 0.001) were significantly correlated with the overall survival of the 304 patients. We selected ␣ 1 -antitrypsin (p ‫؍‬ 0.0001), leukocyte count (p ‫؍‬ 0.066), alkaline phosphatase (p ‫؍‬ 8.3 ؋ 10 ؊8 ), and performance status (p ‫؍‬ 0.003) using multivariate Cox regression analysis and constructed a scoring system (nomogram) that was able to identify a group of high risk patients having a short median survival time of 150 days (95% confidence interval, 123-187 days; p ‫؍‬ 2.0 ؋ 10 ؊15 , log rank test). The accuracy of this model for prognostication was internally validated and showed good calibration and discrimination with a bootstrap-corrected concordance index of 0.672. In conclusion, an increased level of ␣ 1 -antitrypsin is a biomarker that predicts short overall survival of patients with advanced pancreatic cancer receiving gemcitabine monotherapy. Although an external validation study will be necessary, the current model may be useful for identifying patients unsuitable for the standardized therapy. Molecular & Cellular Proteomics 9:695-704, 2010.

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confidence: 99%

Survival Prediction for Pancreatic Cancer Patients Receiving Gemcitabine Treatment

Matsubara

Ono

Honda

et al. 2010

Molecular & Cellular Proteomics

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“…A phase II efficacy component was incorporated in the phase I/II study by allowing additional treatment cycles to be given if the patient had equal or less than grade I toxicity. The principal investigator was also allowed to recommend surgical resection/debulking, and Rexin-G was continued if residual disease was found by histological examination or PET-CT scan (11). An amendment to the New Investigational Drug application was approved by the FDA (BB-IND#11586) in July, 2007, and the clinical protocol (C07-105) was reviewed and approved by the Western Institutional Review Board, Olympia, WA 98502.…”

Section: Case Study and Methodsmentioning

confidence: 99%

Pathotropic targeting advances clinical oncology: Tumor-targeted localization of therapeutic gene delivery

Гордон¹

2010

Oncol Rep

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Abstract. The advent of pathotropic (disease-seeking) targeting has transported genetic medicine across the threshold of history with the progressive clinical validation of Rexin-G, a tumor-targeted nanosized anti-cancer agent. Achieving noteworthy single-agent efficacy and survival benefits in otherwise intractable cancers, the molecular biotechnology platform has stimulated intense interest in the underlying mechanisms-of-action. This report exhibits the effective localization of Rexin-G nanoparticles within a metastatic liver lesion, as observed upon its surgical excision. IntroductionRexin-G is a pathotropically-targeted replication-incompetent retroviral vector encoding a dominant-negative mutant form of the human cyclin G1 gene, an essential component of the executive cell cycle control pathways that are fundamental to cell growth (1,2). By targeting and thus aborting this critical regulatory component of the cell's universal replication machinery, Rexin-G is invariably lethal to cancer cells derived from all three germ layers, including their associated proliferative vasculature, which empowers Rexin-G with potent anti-angiogenic properties (3,4), as well as broad spectrum tumoricidal activity (5-7). Each therapeutic nanoparticle incorporates a highly efficient and exquisitely specific targeting function to seek out and accumulate in cancerous tissues, using the abnormal or 'pathological' properties of the disease itself, specifically, the newly exposed collagenous proteins associated with cancer growth, metastasis, and tumor-associated blood vessel formation (8). The first targeted genetic medicine of its kind to be tested in the clinic (9), Rexin-G has achieved regulatory approval in the Philippines for the treatment of all chemoresistant solid tumors, and is approaching regulatory approval in the USA for pancreatic cancer, osteosarcoma, and soft tissue sarcomas, where it has been granted FDA Fast Track designation and Orphan Drug status, respectively.The clinical performance of Rexin-G is a function of the multiple levels of safety and efficacy embodied in its design engineering (1), as is its broad-spectrum anti-cancer activity (10). In terms of safety: i) the stealth vector platform allows repeated infusions without untoward immune responses; ii) the limitations of the retroviral platform become a virtue, as the vector is capable of enforcing gene expression in proliferative/dividing cells only; iii) the growth-associated designer gene is active against cancer cells and proliferative vasculature but not against normal non-dividing cells; and iv) the pathotropic accumulation in cancerous tissues essentially sequesters the vector away from non-target organs. In terms of efficacy: i) the cell cycle gene knockout provides for broadspectrum anti-cancer activity; while ii) the anti-angiogenic activity destroys tumor-associated vasculature; and iii) the pathotropic targeting leads to accumulation and high local concentrations where it is needed most, i.e., in the tumor microenvironment.In this communication...

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“…The treatment of M1 PDAC usually includes symptom-directed palliative therapies with or without chemotherapy (78), with very low survival rates. It appears that for patients with M1 PDAC the quality of life is by far more important than the quantity of life (79).…”

Section: Resection For M1 Pdacmentioning

confidence: 99%

Onco-surgical Strategies in Pancreatic Ductal Adenocarcinoma

Popescu¹,

Dumitraşcu²

2017

SGO

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Pancreatic ductal adenocarcinoma (PDAC) is an important healthcare problem because is a leading cause of death by cancer. PDAC is a highly lethal disease with a very dismal prognosis. Most patients present advanced disease at diagnosis. The management of a patient diagnosed with PDAC should be discussed in a multidisciplinary team in high-volume centers. Pancreatectomy represents the single hope of long-term survival for a patient with PDAC but the resectability rate is less than 20% of the cases. Several progresses were observed in the last years regarding the surgical and oncological approach for PDAC. The aim of the paper is to make a brief review of the current onco-surgical strategies available for patients with PDAC.

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Metastatic Pancreatic Cancer 2008: Is the Glass Less Empty?

Cited by 16 publications

References 0 publications

Survival Prediction for Pancreatic Cancer Patients Receiving Gemcitabine Treatment

Survival Prediction for Pancreatic Cancer Patients Receiving Gemcitabine Treatment

Pathotropic targeting advances clinical oncology: Tumor-targeted localization of therapeutic gene delivery

Onco-surgical Strategies in Pancreatic Ductal Adenocarcinoma

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