PREFACE

Pancreatic cancer is among the most dreaded cancers due to its refractoriness to conventional antineoplastic treatment. This malignancy's aggressive nature is now challenging researchers to use

pancreatic cancer as a model to test novel therapeutic approaches. New modalities are emerging based on increased understanding of the molecular events that underlie the pathobiology of this disease.

In the first chapter, King et al describe genetic alterations that are common in pancreatic cancer and relates these to the clinical behavior of this malignancy. Advances in molecular pathology will form the basis for screening family members with heritable pancreatic cancer, early diagnosis, choice of treatment based on the molecular composition of tumors, novel treatment modalities and gene therapy.

The role of laparascopy in the management of the pancreatic cancer is discussed by Iannitti et al in the third chapter of this special issue.

Heywood et al then give a historical review of surgical therapy for pancreatic cancer. Disease-free and overall survival with single modality therapy based on surgical procedure are described. Iannitti then reviews the emerging role of laparoscopy in staging, assessment for resectability and palliation. By detecting intraperitoneal disease, laparoscopy has the potential of sparing patients major abdominal surgery in whom metastatic deposits are not apparent by CT scan. Laparoscopy may also define optimal candidates for chemoradiation.

Regine et al review the role of adjuvant therapy following surgical resection. In this timely review, the negative results of the recent European Organization for the Research and Treatment of Cancer are balanced with data from the Gastrointestinal Study Group. The newly activated Radiation Therapy Oncology Group (RTOG)/Intergroup adjuvant trial is also described. Accrual to this newly opened trial, evaluating gemcitabine to reduce systemic relapse, is a current priority for those involved in the care of patients with pancreatic cancer.

Breslin et al then review the M.D. Anderson Cancer Center's provocative data on neoadjuvant chemoradiation for pancreatic cancer. Based on their sentinel work, neoadjuvant treatment may become the new standard in potentially resectable pancreatic cancer. Neoadjuvant treatment has the potential to increase resectability, decrease local recurrence and improve survival. The use of gemcitabine as a radiosensitizer is also described.

Paclitaxel as a radiation sensitizer is then described by Safran et al from the Brown University Oncology. Paclitaxel may synchronize cells in the most radiosensitive phase of the cell cycle and activate p53 independent apoptotic pathways. Based on encouraging phase I/II data, paclitaxel and concurrent radiation is being evaluated by the RTOG in a national phase II study for locally advanced pancreatic cancer. Willett et al then review the Massachusetts General Hospital (MGH) experience with intraoperative radiation. Preclinical rationale, technical aspects and clinical data are described. The current approaches to treatment at MGH are described.

Unfortunately, the majority of patients with pancreatic cancer develop systemic metastases. Blaszkowsky gives a comprehensive review on single agent and combination chemotherapy and hormone

therapy, and introduces the potential role of biologic and gene therapy. Butera et al then review novel, non-cytotoxic approaches, that are emerging as important new treatment modalities for pancreatic cancer. The use of farnesyl transferase inhibitors, matrix metalloproteinase inhibitors and Her-2/neu antibodies are described. In the final chapter, Pearson et al gives a comprehensive review on ongoing and planned gene therapy approaches in pancreatic cancer.

Important new treatment modalities are therefore rapidly emerging in pancreatic cancer. These innovations are bringing new treatment options for clinicians and renewed hope for patients.

Howard Safran M.D.
Brown University Oncology Group