Changing the Paradigm in Conducting Randomized Clinical Studies in Advanced Pancreatic Cancer: An Opportunity for Better Clinical Development

Medical Oncology Department, Vall d'Hebron University Hospital, Barcelona, Spain.
Journal of Clinical Oncology (Impact Factor: 18.43). 10/2009; 27(33):5487-91. DOI: 10.1200/JCO.2009.23.3098
Source: PubMed

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    • "Novel biologic agents have failed categorically—the suite of negative pancreatic cancer trials evaluating cytotoxic and biologic agents, either alone or in combinations, leaves gemcitabine monotherapy as the current standard of care for all but the very best of performance status patients. A thoughtful editorial recently published in the Journal of Clinical Oncology has outlined the trials and tribulations of pancreatic cancer research and has suggested modifications to improve clinical trial design and outcomes including: consideration of randomized phase II designs, better patient selection and stratification, questioning gemcitabine as the backbone treatment, better and quicker access to completed trial results, and the identification of surrogate endpoints similar to three year DFS in metastatic colon cancer [45]. "
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    ABSTRACT: Pancreatic cancer is one of the most lethal cancers, where curative surgical resections are rare and less than 5% of patients experience long-term survival. Despite numerous clinical trials, improvements in the systemic treatment of this disease have been limited. Gemcitabine, a nucleoside analogue, is still considered the standard of care chemotherapy for most patients in the advanced disease setting. To exert its cytotoxic effects, gemcitabine must enter cells via nucleoside transporters, most notably human equilibrative nucleoside transporter 1 (hENT1). Increasingly strong evidence suggests hENT1 is a prognostic biomarker in gemcitabine-treated pancreatic cancer, and may well be a predictive biomarker of gemcitabine efficacy. In this review, we synthesize the literature surrounding hENT1 in pancreatic cancer, identify the key outstanding questions, and suggest strategies to prospectively evaluate the clinical utility of hENT1 in future clinical studies.
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    ABSTRACT: Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.
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