Pancreatic Cancer

With the diagnosis of pancreatic cancer, the ma-jority of patients are faced with an unexpected tragedy. There is a persistently low rate of curabil¬ity, a so-called case fatality rate of around 95%.
Complete resection is the prerequisite for cu-ration, but only one-fifth of the patients are con¬sidered for surgical therapy. Even so, only about half of these individuals finally undergo success¬ful, complete resection. Whereas nowadays sur¬gery can be performed with low rates of periop-erative morbidity and mortality at experienced high-volume centers, postoperative relapses are observed frequently. Neoadjuvant strategies to improve surgical resectability and the overall cure rate remain experimental, but due to the re¬sults of different trials, adjuvant treatments strat¬egies are becoming standard worldwide. Trans¬atlantic differences in the interpretation of study results with the use of chemoradiation probably will be overcome by the recent results of adjuvant chemotherapy in patients with adenocarcinoma of the pancreas, which have shown significant benefit in relapse-free survival, 3- and 5-year survival, and therefore—most likely—cure [1]. Ongoing studies will definitely clarify the role and kind of chemotherapy to be recommended for patients resected completely (R0) and those with microscopic involvement of the resection margin (R1).
For the majority of patients with nonresect-able, locally advanced, metastasized, or relapsing pancreatic cancer, progress has been limited for several years. It took more than 10 years from the approval of gemcitabine for the treatment of ad¬vanced adenocarcinoma of the pancreas—and a great number of large-scaled phase III trials—be-fore a second improvement in systemic therapy was implemented in patient care.
Erlotinib, a tyrosine kinase inhibitor blocking epidermal growth factor (EGF) receptor-medi¬ated downstream signaling, succeeded in im¬proving outcome in patients with advanced pan¬creatic cancer when applied in combination with gemcitabine, with a hazard ratio of 0.8 resulting in a 7% excess in 1-year survival as compared to gemcitabine plus placebo [2]. Due to this study, erlotinib obtained approval in the United States and Europe and is on the way to finding its place in routine treatment.
Confirming former nonsignificant results of gemcitabine in combination with capecitabine, it was recently demonstrated that this combination of cytotoxic drugs improved median and 1-year survival in a prospective randomized but non-placebo-controlled trial [3].
The impact of these data for standard care of patients with adenocarcinoma of the pancreas cancer needs to be defined. As adverse effects of cytotoxic drugs and targeted therapies differ, tai-loring patient-specific first-line therapy has be-come a challenge for oncologists.
An improvement in quality of life, estimated by the clinical benefit response, occurs in a rel-evant proportion of patients due to first-line therapy with gemcitabine [4]. Therefore an in-creasing number of patients with pancreatic can-cer progressing while on first-line therapy need to be considered for second-line therapy, based on their good performance status. The identifi¬cation of principally active cytotoxic drugs, such as oxaliplatin (together with folinic acid and fluorouracil) or taxanes, antibodies, and small molecules, such as erlotinib and sorafenib, offer second-line treatment alternatives that have to undergo evaluation in clinical trials. Initial re¬sults favor oxaliplatin-based therapy [5, 6].

These small steps forward in the systemic therapy of pancreatic cancer give rise to some prudent optimism. In order to alter the perspec-tives of patients with pancreatic cancer, further understanding of the basic aspect of disease development as well as methods for screening or early diagnosis of this disease have to be de-veloped. It is the aim of this issue of Recent Re¬sults in Cancer Research to compile the available knowledge concerning pancreatic cancer.