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Nonmetastatic Pancreatic Cancer: Many Trials, Little Progress

Technische Universität München, München, Germany

To the Editor:

The phase II trial by Small et al¹ investigates full-dose gemcitabine with concurrent radiation therapy in patients with nonmetastatic pancreatic cancer. The rationale of this approach was to combine local disease control (radiation) with systemic disease control (gemcitabine). Local disease control in pancreatic cancer is of little relevance, given that the vast majority of patients die of metastatic disease. Nonetheless, the authors are correct in stating that "both localized treatment and systemic control for patients with nonmetastatic but unresectable disease might enhance overall survival and improve the possibility for curative surgical resection." This approach is usually termed neoadjuvant therapy.

Phase I/II trials of neoadjuvant therapy in pancreatic cancer will not advance patient care as long as we do not have solid evidence that neoadjuvant therapy is of any benefit (or at least not harmful) for pancreatic cancer patients. There are numerous phase I/II trials of neoadjuvant therapy in pancreatic cancer² whose conclusions can be copied and pasted: "this regimen is feasible and safe and additional randomized trials are warranted." Unfortunately, none of the published articles followed up on their suggestion of a randomized trial. Besides the ethical considerations, one must also look at the direct and indirect health care costs of those trials. It is not encouraging to state that "a trial using a similar protocol plus bevacizumab" is currently ongoing,¹ as one already knows the concluding remarks of this study.

We need some progress in pancreatic cancer therapy—a disease so difficult to treat that a drug (gemcitabine) with a 5% to 10% response rate^1,3 is considered "effective."¹ Neoadjuvant therapy would have the potential to move us forward, with surgical resections being noncurative in the vast majority of patients,⁴ and adjuvant therapies not being possible in a significant number of patients.⁵

Neoadjuvant therapy "might enhance overall survival and improve the possibility for curative surgical resection" in pancreatic cancer: it might, or it might not. We need different trials to answer this relevant question.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Small W Jr, Berlin J, Freedman GM, et al: Full-dose gemcitabine with concurrent radiation therapy in patients with nonmetastatic pancreatic cancer: A multicenter phase II trial. J Clin Oncol 26:942-947, 2008[Abstract/Free Full Text]

2. Kleeff J, Friess H, Buchler MW: Neoadjuvant therapy for pancreatic cancer. Br J Surg 94:261-262, 2007[CrossRef][Medline]

3. Yip D, Karapetis C, Strickland A, et al: Chemotherapy and radiotherapy for inoperable advanced pancreatic cancer. Cochrane Database Syst Rev 3:CD002093, 2006[Medline]

4. Esposito I, Kleeff J, Bergmann F, et al: Most pancreatic cancer resections are R1 resections. Ann Surg Oncol 15:1651-1660, 2008[Abstract/Free Full Text]

5. Wayne JD, Abdalla EK, Wolff RA, et al: Localized adenocarcinoma of the pancreas: The rationale for preoperative chemoradiation. Oncologist 7:34-45, 2002[Abstract/Free Full Text]

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  William Small, Jr, Jordan Berlin, Gary M. Freedman, Andre A. Konski, Theodore S. Lawrence, Mark S. Talamonti, Mary F. Mulcahy, A. Bapsi Chakravarthy, Mark M. Zalupski, Philip A. Philip, Timothy J. Kinsella, Nipun B. Merchant, John P. Hoffman, Al B. Benson, III, and Cornelius J. McGinn
  JCO 2008 26: 3100-3101 [Full Text]

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  William Small, Jr, Jordan Berlin, Gary M. Freedman, Theodore Lawrence, Mark S. Talamonti, Mary F. Mulcahy, A. Bapsi Chakravarthy, Andre A. Konski, Mark M. Zalupski, Philip A. Philip, Timothy J. Kinsella, Nipun B. Merchant, John P. Hoffman, Al B. Benson, Steven Nicol, Rong M. Xu, John F. Gill, and Cornelius J. McGinn
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