Adjuvant therapy for pancreatic adenocarcinoma: What have we learned since 1985?

Purpose: To review developments relevant to pancreatic adjuvant therapy since the publication of the Gastro-intestinal Tumor Study Group (GITSG) trial of adjuvant therapy for pancreatic cancer in 1985. Results: Our understanding of the pathology, surgical management, clinical and pathologic prognostic factors, potential importance of adjuvant therapy, and optimal design of adjuvant therapies have all undergone major evolution. Available data suggest: (1) the morbidity of pancreaticoduodenectomy has been reduced substantially, especially in major referral centers; (2) physicians, patients, and families recognize the importance of clinical trials and substantial numbers of patients are available for such trials; (3) factors such as tumor size, margin status, nodal involvement, histologic differentiation, and blood loss at surgery have an impact on postoperative outcomes; (4) the use of gemcitabine and patient-specific, anatomic planning for conformal radiotherapy has the potential to radically alter the adjuvant paradigm; (5) vaccine therapies have completed Phase I testing and are being incorporated into Phase 11 trials; and (6) careful application of relevant statistical principles is necessary to avoid the execution of ambiguous or uninterpretable trials. Conclusions: The need for effective adjuvant therapy is undisputed, because surgery alone is inadequate. In-creasing numbers of patients are undergoing and recovering from surgery who are willing to consider clinical trials. Major cooperative group and single-institution efforts recently completed, ongoing, or currently planned using improved stratification for prognostic subsets, translational approaches based on molecular biology and/or genetic engineering, and newer chemoradiotherapeutic regimens are rapidly changing the landscape of this clinical arena into one of promise and possibility. (C) 2003 Elsevier Inc.