A phase III trial in Japanese patients with stage I-III pancreatic cancer shows that postoperative (adjuvant) treatment with a chemotherapy drug called S-1 substantially increases overall survival rates compared to treatment with the standard postoperative drug gemcitabine.

The findings point to  a more effective treatment option for a subset of patients with pancreatic cancer, particularly for Asian patients. (Previous studies have shown that S-1 has more harmful side effects in Caucasian patients.) “Our survival data were much stronger than expected.

Based on these results, we hope that guidelines for standard postoperative therapy for pancreatic cancer in Japan will be changed to replace gemcitabine with S-1as singleagent therapy,” said lead author Katsuhiko Uesaka, MD, PhD, medical deputy director at Shizuoka Cancer Center Hospital.

The drug could also be a promising treatment option for Asian patients in other parts of the world. S-1 is currently available in several Asian countries and most of Europe, though it is not yet approved in the United States. 

In the United States, pancreatic cancer is the fourth leading cause of cancer-related death. More than half of cases are diagnosed at an advanced stage, for which the 5-year survival rate is below 2 percent.

Because pancreatic cancer is typically detected after it has spread beyond the pancreas, only 20-30 percent of patients are candidates for surgery.

Following surgery patients typically receive the adjuvant chemotherapy drug gemcitabine, which has
been shown to lengthen survival by several months compared to surgery alone. In Asian patients with inoperable pancreatic cancer, previous studies have suggested that outcomes with S-1 are comparable to outcomes with gemcitabine.

In the present study, conducted in Japan, investigators randomly assigned 385 patients to postoperative treatment with gemcitabine or S-1. An interim analysis of trial data found that patients who received S-1 had a 44 percent lower risk of death than patients who received gemcitabine.

The two-year survival rates were 70 percent and 53 percent for S-1 and gemcitabine, respectively. Relapse rates were also lower in theS-1 arm. The two year relapsefree survival rates were 49 percent and 29 percent for S-1 and gemcitabine, respectively. S-1 was well-tolerated, with over 70 percent of patients completing the therapy. 

Based on these interim analysis findings, the safety and efficacy committee that monitors this trial recommended early reporting of the results to speed adoption of S-1 as the new standard postoperative treatment for patients with pancreatic cancer.

The investigators will continue to follow the study participants for at least five years. Due to metabolic differences between Asian and Caucasian ethnic groups, gastrointestinal side effects of S-1 are more severe among Caucasians, requiring use of lower doses of the drug for Caucasian patients.

For those reasons, the findings of this study are not immediately applicable to non-Asian populations, but Uesaka hopes that similar studies of S-1 as adjuvant therapy for pancreatic cancer will soon be conducted in Europe and the United States among Caucasian patients, with adjustment of S-1 dose. 

S-1 is an oral chemotherapy drug prescribed in Japan to treat stomach, colorectal, pancreatic, biliary, head and neck, non-small cell lung, and metastatic breast cancer. While it is not yet approved in the United States, a phase III clinical trial exploring S-1 for treatment of patients with stomach cancer is already under way.

Source: ASCO