Non-surgical treatments of pancreatic cancer

Abstract

Although pancreatic cancer (PC) continues to be a formidable disease, numerous treatment strategies are evolving and it is hoped that these will result in improved patient survival. Only surgical resection offers the opportunity for cure, but the prognosis of resected patients remains unfavorable because of postoperative recurrence. Accordingly, to improve the survival of PC patients, it is essential to develop effective non-surgical treatments for this disease. Radiotherapy (RT) alone does not have a significant clinical impact in PC, but when combined with chemotherapy (CHT), it provides a survival benefit in both locally unresectable and adjuvant settings of PC. However, to establish optimal methods of combining RT with CHT, newer approaches, such as specialized RT techniques and new CHT agents, are actively being pursued. CHT for PC has only limited value in clinical practice, because of the lack of any agent with a truly high level of activity. The identification of more effective new agents is therefore a high priority, and the enrollment of PC patients with metastatic disease into well designed clinical trials is essential. The novel nucleoside analog, gemcitabine, appears to have the potential to produce better results than those achieved over the last 35 years with 5-fluorouracil (5-FU). Moreover, increased understanding of the biology of PC should facilitate the development of entirely novel treatment options. We must continue to actively search for more effective nonsurgical treatments for PC.

A phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with locally advanced pancreatic cancer

“…Currently, concomitant external beam radiotherapy and chemotherapy has been accepted as the standard therapy for patients with locally advanced nonresectable PC (Okada, 1999), because randomized trials have demonstrated improved survival with CRT compared with that by either radiation alone or chemotherapy alone (Moertel et al, 1969(Moertel et al, , 1981Gastrointestinal Tumor Study Group, 1988), although the role of adjuvant CRT for patients with resectable PC remains controversial. To intensify the treatment efficacy, various anticancer agents, and radiation schedules are being examined in clinical trials.…”

“…Among these patients, roughly half are diagnosed with locally advanced disease radiographically confined to the pancreas and surrounding tissues (Okada, 1999). In the patients with locally advanced PC, prospective randomized trials conducted by Moertel et al (1969) and the Gastrointestinal Tumor Study Group (GITSG) (Moertel et al, 1982;Gastrointestinal Tumor Study Group, 1988) have demonstrated that the combination of radiotherapy and chemotherapy (chemoradiotherapy; CRT) resulted in significantly better survival than either radiotherapy alone or chemotherapy alone.…”

“…In patients with resectable PC, the randomised controlled trial conducted by GITSG demonstrated a significant survival advantage for patients receiving adjuvant CRT (Gastrointestinal Tumor Study Group, 1987), but the European Study Group for Pancreatic Cancer (ESPAC) trial failed to show the survival benefit of adjuvant CRT (Neoptolemos et al, 2001). Thus, CRT is presently accepted as the standard treatment for locally advanced PC (Okada, 1999), but the role of adjuvant CRT for patients with resectable PC remains controversial. However, optimal CRT regimens have not yet been determined, although various anticancer agents and radiation schedules are being examined in clinical trials.…”

Phase II study of radiotherapy combined with gemcitabine for locally advanced pancreatic cancer

“…For patients with locally advanced pancreatic cancer, chemoradiotherapy has been accepted as standard treatment because the results of previous randomised trials have indicated that concurrent external-beam radiation therapy and 5-fluorouracil (5-FU) therapy results in a significantly longer survival time than radiotherapy (Moertel et al, 1969;Gastrointestinal Tumor Study Group, 1981) or chemotherapy alone (Gastrointestinal Tumor Study Group, 1988). In attempts to improve the efficacy of the treatment, numerous trials using modified approaches of chemoradiotherapy have been conducted (Chakravarthy and Abrams, 1997;Okada, 1999). However, there has not yet been a regimen that has demonstrated superiority over conventional chemoradiotherapy performed in randomised controlled trials.…”

Phase I Study of Hyperfractionated Radiation Therapy with Protracted 5-Fluorouracil Infusion in Patients with Locally Advanced Pancreatic Cancer

“…In the treatment of locally advanced, unresectable pancreatic cancer, radiotherapy with concomitant chemotherapy has been the treatment of choice since it offers better survival rates when compared to treatment by radiotherapy or chemotherapy alone [1, 2]. However, improvement in chemoradiotherapy for pancreatic cancer is necessary because chemoradiotherapy has achieved only modest improvements in median survival and minimal increases in long-term survival [3]. …”