Adjuvant therapy for pancreatic cancer: back to the future

Abstract

Purpose: The role of adjuvant therapy in the management of pancreatic cancer, resected with curative intent, remains controversial. This editorial review updates the status of adjuvant therapy in this context and introduces the first North American co-operative group study in this arena in roughly 20 years.

Results: To the extent that there has been a "standard" of care in this context, it has been defined in large part by the early work of the Gastrointestinal Study Group (GITSG). Their trial was activated in the mid 1970's using split course radiation therapy and bolus 5-FU. In the intervening 20 + years the morbidity/mortality of pancreaticoduodenectomy (PDD) has been dramatically reduced; concurrently, understanding of prognostic factors impacting on outcomes for resected patients has been significantly enhanced. In major centers the mortality of PDD is roughly 1% and survival has been shown to correlate with a number of factors including tumor size, nodal involvement, and margin status. With currently available techniques doses of continuous course radiation therapy in the range of 50-55 Gy to sites of pancreatic tumor resection and adjacent lymph node regions have been given in a number of trials with acceptable morbidity. 5-FU sequencing and administration have been advanced and gemcitabine, an agent with clear radiosensitizing properties, has been approved for use against pancreatic cancer.

Conclusions: Following PDD increasing numbers of physiologically intact patients are confronting the survival statistics associated with resected pancreatic cancer. Their interest in improved therapeutic outcomes, combined with the noted improvements in radiation and chemotherapeutic management, has set the stage for renewed and intensified study. Accordingly, the intergroup mechanism of the Cancer Therapy and Evaluation Program (CTEP) of the NCI has designed, approved, and activated a modern Phase III, adjuvant protocol incorporating recently gained knowledge in this management context. Prospective randomization will be utilized to compare gemcitabine and 5-FU as single agents before and after chemoradiotherapy with 5-FU. Successful and timely completion of this newly activated intergroup study, RTOG 97-04, will establish a current, cooperative group experience, data base, and standard in the context of adjuvant therapy for pancreatic cancer and serve to provide momentum for further studies.