Combination chemotherapy with gemcitabine and S-1 for advanced pancreatic cancer

The incidence and mortality of pancreatic cancer has increased very rapidly in Japan. The five-year survival rate is still poor at less than 10%, because it is commonly considered to be linked to a high incidence of distant metastasis even at the initial diagnosis as well as to the tumor's resistance to anticancer agents. Although gemcitabine has been the most widely used chemotherapeutic agent in patients with advanced pancreatic cancer (APC), gemcitabine monotherapy has obvious limitations. Therefore, various combinations with other agents have been investigated to improving the survival of patients with APC. Under these circumstances, we conducted a phase I /II trial of gemcitabine with S-1, an oral fluorouracil derivative, to determine the maximum tolerated dose and to evaluate the activity and toxicity of such a combination in patients with APC. S-1 was administered orally twice daily each day for 14 days and gemcitabine on days 8 and 15 of each cycle, and this cycle was repeated every 21 days. As a result, S-1 30 mg/m2 orally twice daily and gemcitabine 1,000 mg/m2 were selected as the recommended dose. The toxicities observed were mainly hematological ones with mild non-hematological toxicities. An encouragingly high response rate was observed. This result is very promising, but the survival benefit in comparison with gemcitabine monotherapy needs to be confirmed in a future randomized clinical trial.