New therapies for pancreatic cancer: current standard.

With regard to resectable disease, two recent phase III randomized trials showed that postoperative chemotherapy, either 5fluorouracil or gemcitabine, significantly prolongs overall and disease-free survival with respect to observation alone [1, 2]. A Radiation Therapy Oncology Group (RTOG) phase III randomized trial showed significantly better survival after gemcitabine chemotherapy with respect to continuous infusion 5-fluorouracil in the subgroup of patients with pancreatic head cancer [3]. However, in this trial the dose of 5fluorouracil was suboptimal, representing about 60% of the potential dose previously used in advanced disease [4] and a definitive conclusion about the superiority of gemcitabine can not be drawn. The findings from these trials confirmed that failure to prevent metastases represents the main pattern of disease recurrence even in the early stages of pancreatic carcinoma. While local recurrence is also the rule, isolated local failure occurred in less than one-third of cases. Accordingly, systemic chemotherapy appears to have a stronger rationale as a first postoperative therapy with respect to local treatment and either gemcitabine alone or full dose 5-fluorouracil may be considered a standard. An ongoing European Study Group of Pancreatic Cancer (ESPAC-3) trial comparing gemcitabine to 5-fluorouracilleucovorin postoperative chemotherapy should provide further information for resolving this controversy. The use of postoperative combination chemotherapy outside of clinical trials is unjustified. No firm conclusion about the role of modern chemoradiation after systemic chemotherapy is possible because no information from phase III trials is available. In fact, randomized trials comparing chemoradiation with observation used outdated modalities, for both radiation and chemotherapy, and administered this local treatment as an upfront postoperative treatment [2, 5, 6]. Despite these methodological pitfalls, controversial results were observed. Thus, it is the author's opinion that modern chemoradiation after systemic chemotherapy has a role in the therapeutic management of this disease. An ongoing European Organisation for Research and Treatment of Cancer (EORTC) trial, comparing four cycles of gemcitabine with two cycles of gemcitabine followed by chemoradiation will contribute to better clarifying this issue.