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Optimum Cytotoxic Therapy for Advanced Pancreatic Cancer

  • Sameer P. Desai
  • Mark M. Zalupski
Part of the M. D. Anderson Solid Tumor Oncology Series book series (MDA)

The effectiveness of treatment for pancreatic cancer is limited by the combination of early metastases and de novo resistance to cytotoxic therapies, rendering most patients candidates for palliative systemic therapy. Despite more than four decades of study, the benefit of systemic therapy is limited to a minority of patients and the impact on survival is marginal. In the pre-gemcitabine era, 5-fluorouracil (5FU) was commonly used, either alone or as a component of combination therapy. Based on low response rates, toxicity, and minimal impact on survival, some even questioned the use of cytotoxic treatment. However, following initial studies, gemcitabine quickly became a standard treatment for pancreatic cancer based on the combination of tolerability and symptom control. While acknowledging an overall improvement with gemcitabine, there clearly remains a need for more effective therapies. Increasingly, phase I and II studies have been performed in this disease, investigating dose and schedule questions of gemcitabine delivery and/or the addition of one or more drugs to gemcitabine. Reports from many of these trials describe improved efficacy or increased tolerance. Confirmatory phase III studies, however, have generally defined these apparent gains as either modest or nonexistent. The rapid introduction of a wide array of targeted agents into the clinic is leading to a new generation of studies, bringing hope to the many patients suffering from this difficult disease.

The goals of therapy in pancreatic cancer include symptom control and improved survival. Recent phase III trials emphasized overall survival as the primary endpoint. As data have accumulated, phase III trials have increased in size to identify disappointingly small improvements in survival as statistically significant. Additionally, as options for treatment increase, second-line therapy may have an impact on a survival endpoint, as has been demonstrated in colorectal cancer. Quality of life (QOL) measures support the use of treatment as compared to supportive care only in advanced disease but are difficult to interpret in phase II and III trials due to subjectivity, therapy related toxicities and patient attrition. Clinical benefit response (CBR), a measure of performance status (PS), pain intensity and control, and weight, have been employed in pancreatic cancer trials but its use requires initial symptoms and a somewhat subjective assessment of PS and pain control. Progression-free survival often parallels QOL and CBR but is subject to the inherent difficulties in objectively defining progression and the intervals at which disease is evaluated.

Keywords

Pancreatic Cancer Clin Oncol Febrile Neutropenia Advanced Pancreatic Cancer Best Supportive Care 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science + Business Media, LLC 2008

Authors and Affiliations

  • Sameer P. Desai
    • 1
  • Mark M. Zalupski
    • 1
  1. 1.Division of Hematology-OncologyUniversity of MichiganAnn ArborUSA

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