Phase II Trial of Cetuximab, Gemcitabine, and Oxaliplatin Followed by Chemoradiation With Cetuximab for Locally Advanced (T4) Pancreatic Adenocarcinoma: Correlation of <i>Smad4(Dpc4)</i> Immunostaining With Pattern of Disease Progression

Crane, Christopher H.; Varadhachary, Gauri R.; Yordy, John S.; Staerkel, Gregg; Javle, Milind; Safran, Howard; Haque, Waqar; Hobbs, Bridgett D.; Krishnan, Sunil; Fleming, Jason B.; Das, Prajnan; Lee, Jeffrey E.; Abbruzzese, James L.; Wolff, Robert A.

doi:10.1200/jco.2010.33.8038

Cited by 260 publications

(186 citation statements)

References 17 publications

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“…In patients who had local-only disease, 22 % had loss of Smad-4 immunolabeling at autopsy, whereas 78 % of patients with metastatic disease had Smad-4 loss at autopsy (p =0.032) [46]. This finding was validated in a series of patients enrolled in phase II chemoradiation trial for locally advanced pancreatic cancer, where Smad-4 expression was significantly correlated with a local pattern of failure [47]. Further confirmatory studies are needed, but this marker has potential use as an early indicator for patients who may require more aggressive local-regional therapy upfront.…”

Section: The Era Of Modern Radiotherapysupporting

confidence: 52%

The role of adjuvant chemoradiation in the treatment of pancreatic cancer

2013

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The high rates of mortality due to pancreatic cancer have shown minimal improvement over the past few decades. Even in the most favorable subset of patients, those who are able to receive a pancreatoduodenectomy, outcomes are poor. In addition to high rates of distant metastases, pancreatic cancer is locally aggressive, with high recurrence rates postresection. The role of adjuvant treatment using chemoradiation has been shown to improve local control and survival in pancreatic cancer, but its role remains unclear compared with chemotherapy alone given the high rates of distant failure. This review will present the historically important trials utilizing adjuvant chemoradiation, discuss more contemporary studies, and outline the future direction and results of more recent reports utilizing novel chemotherapeutic agents and advanced radiotherapy techniques in the adjuvant setting.

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Section: The Era Of Modern Radiotherapysupporting

confidence: 52%

The role of adjuvant chemoradiation in the treatment of pancreatic cancer

2013

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“…3 This was supported by the report of a correlation of the pattern of disease-related death and SMAD-4 expression in locally advanced pancreatic cancer in a cohort of patients treated on a phase II trial at The University of Texas MD Anderson Cancer Center. 4 This trial could be the first step in the validation of SMAD-4 as a medically necessary biomarker in pancreatic cancer treatment.…”

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confidence: 99%

Is Personalization of Care Coming to Pancreatic Oncology?

Crane

2012

Ann Surg Oncol

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The results of a phase II trial evaluating adjuvant treatment using a novel way of administering gemcitabine with radiation in patients with resected pancreatic cancer are presented in this issue of the Annals of Surgical Oncology. The trial was designed to evaluate local tumor control as the primary endpoint, using historical local tumor control rates of less than 60 % derived from results reported from cooperative group trials and seeking to show a 2-year local tumor control rate of over 80 % with this novel regimen. The authors reported that the local tumor control rate was apparently improved, without impacting overall survival.

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“…Importantly, the majority of human epithelial cancers are marked by functional activation of growth factors and receptors of the EGFR. Targeting the EGFR is currently available for the treatment of different types of epithelial cancers, such as non-small-cell lung cancer, squamous cell carcinoma of the head and neck, colorectal cancer, and pancreatic cancer (3)(4)(5)(6). The treatment demonstrated that EGFR inhibitors bind to the extracellular domain of the EGFR when it is in the inactive configuration, compete for receptor binding by occluding the ligand-binding region, and thereby directly block ligand-induced EGFR tyrosine kinase activation on cancer cells (7,8).…”

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confidence: 99%