Adjuvant chemotherapy with the oral fluoropyrimidine S-1 improved survival versus standard postoperative gemcitabine in Asian patients with pancreatic cancer, according to an interim analysis from a phase III trial conducted in Japan.
Katsuhiko Uesaka, MD, PhD
Adjuvant chemotherapy with the oral fluoropyrimidine S-1 improved survival versus standard postoperative gemcitabine in Asian patients with pancreatic cancer, according to an interim analysis from a phase III trial conducted in Japan. The data were presented at a press briefing ahead of the 2013 Gastrointestinal Cancers Symposium, held from January 24-26 in San Francisco, California.
“S-1 may be considered the new standard treatment for resected pancreatic cancer patients, at least in Japan,” said lead author Katsuhiko Uesaka, MD, PhD, medical deputy director at Shizuoka Cancer Center Hospital in Japan.
It has not yet been determined whether the survival benefit with adjuvant S-1 will be experienced in Caucasian populations. However, it is known that, compared with Asians, Caucasians receiving S-1 develop more severe gastrointestinal toxicities due to metabolic differences between the populations. For this reason, lower doses of S-1 might be required in Caucasian patients, which could affect the drug’s efficacy.
“The results that were presented are very impressive, and I think will lead to a lot more discussion as to whether or not S-1 can be developed in the US population…I think it will have to come to a clinical trial to really determine that,” said Kenneth H. Yu, MD, of Memorial Sloan-Kettering Cancer Center, who is an expert in treating pancreatic cancer and presented a separate study at the press briefing.
In their phase III study, Uesaka et al randomized 378 Japanese patients with stage I-III pancreatic cancer to adjuvant chemotherapy with S-1 (80 mg -120 mg/day, 4 weeks on, 2 weeks off, for 4 courses; n = 187) or gemcitabine (1000 mg/m2 on days 1, 8, and 15, repeated every 4 weeks for 6 courses; n = 191).
At the first interim analysis (180 deaths), the risk of death was 44% lower in the S-1 arm versus the gemcitabine group (hazard ratio = 0.56; 95% CI, 0.42-0.74; P <.0001). The 2-year overall survival rate was 70% with S-1 versus 53% with gemcitabine.
Toxicities with S-1 were manageable overall, and more than 70% of patients receiving the drug completed treatment. In the category of grade 3/4 toxicities, rates of leukopenia, thrombocytopenia, anemia, and elevated aspartate aminotransferase (AST) levels were higher with gemcitabine, and rates of fatigue and anorexia were higher with S-1.
The positive interim results led an independent data monitoring committee to recommend publishing the data to accelerate approval of S-1 in this setting. The researchers plan to continue following patients in the trial for a minimum of 5 years.
S-1 is an oral formulation that consists of three pharmacological compounds: tegafur, gimeracil, and oteracil. In the bloodstream, cells convert tegafur into 5-fluorouracil (5-FU), which is FDA-approved to treat pancreatic cancer. The additional components, gimercal and oteracil, are included to enhance the efficacy and control the side effects of tegafur.
In Japan, S-1 is approved to treat several cancers, including stomach, colorectal, pancreatic, biliary, head and neck, non—small cell lung, and metastatic breast. While the drug has no FDA-approved indications, “[S-1] is in clinical development with the potential for future licensing in the United States,” according to Neal J. Meropol, MD, who moderated the Gastrointestinal Cancers Symposium press briefing and is the Lester E. Coleman, Jr Professor of Cancer Research and Therapeutics, and chief of the Division of Hematology and Oncology, at University Hospitals Case Medical Center and Case Western Reserve University in Cleveland, Ohio.
Uesaka K, Fukutomi A, Boku N, et al. Randomized phase III trial of adjuvant chemotherapy with gemcitabine versus S-1 for patients with resected pancreatic cancer (JASPAC-01 study). Presented at: 10th Annual Gastrointestinal Cancers Symposium; January 24-26, 2013; San Francisco, CA. Abstract 145.