Advanced pancreatic cancer still has a dismal prognosis. For the past 15 years, gemcitabine has been the standard of care for this disease providing clinical benefit and a median overall survival of slightly more than 6 months. Many compounds have been examined in combination with gemcitabine, but only the addition of the epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib, led to a significant improvement in overall survival of the patients.1 However, the absolute improvement was only in the range of several days in the intention to treat population. A subgroup of patients, namely those who developed a skin rash in response to erlotinib, seemed to benefit more from the addition of the drug. Recently, a combination of 5-fluorouracil, oxaliplatin and irinotecan, the so-called FOLFIRINOX regimen, showed for the first time a marked improvement of overall survival (OS) in patients with metastatic pancreatic cancer compared with single-agent gemcitabine.2 This finding has two implications: Pancreatic cancer is not as chemotherapy-resistant as previously thought, and gemcitabine may not be the ideal combination partner for other chemotherapeutic agents in pancreatic cancer. How to proceed after failure of first-line chemotherapy in pancreatic cancer is still an open question.

Heinemann and colleagues3 investigated a sequential treatment with conventionally dosed gemcitabine, or capecitabine plus erlotinib, followed by the comparator cytostatic …