1. Patients who received adjuvant S-1 had prolonged overall survival and relapse-free survival compared to those who were managed with clinical observation.

2. The most common grade 3-4 adverse events in the S-1 group were neutropenia and biliary tract infection.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Biliary tract cancer has a reported 5-year overall survival of approximately 30-50%. The study (ASCOT) aimed to analyze the use of S-1, a combination oral anti-cancer drug, as adjuvant therapy following the resection of biliary tract malignancies. Patients with confirmed biliary tract cancer were randomized to either observation or 4 cycles of S-1. Treatment was administered orally twice daily for 4 weeks with 2 weeks of rest. This study found that the 3-year overall survival rate was higher in the S-1 group compared to the observation-only group. In addition, the relapse-free survival rate was higher in the S-1 group. Overall, treatment with S-1 was well tolerated. The most common grade 3-4 adverse events in the S-1 group were low neutrophil count and biliary tract infection. Limitations of this study include the potential lack of generalizability as the experiments were conducted only in Japan. Nevertheless, this study provides promising evidence for the use of adjuvant S-1 following the resection of biliary tract cancer.

Click to read the study in The Lancet

Relevant Reading: Effect of Adjuvant Chemotherapy With Fluorouracil Plus Folinic Acid or Gemcitabine vs Observation on Survival in Patients With Resected Periampullary Adenocarcinoma

In-Depth [randomized controlled trial]: This phase 3 drug trial (ASCOT) evaluated the use of adjuvant S-1 versus observation in resected biliary tract cancer. Eligibility criteria included age 20-80 years old with histologically confirmed adenocarcinoma or adenosquamous carcinoma that had undergone no local residual tumour resection or microscopic residual tumour resection. A total of 440 participants were randomly assigned 1:1 to either observation (n = 222) or adjuvant S-1 (n = 218). S-1 was administered orally twice daily for 4 cycles (4 weeks on followed by 2 weeks of rest). Dosing was based on body surface area (40 mg, 50 mg, or 60 mg). The primary endpoint was overall survival. Study results demonstrate the 3-year overall survival was lower in the observation group (adjusted HR 0.69, 95% CI 0.51-0.94, one-sided p=0.0080) at 67.6% versus 77.1% in the S-1 group. Relapse-free survival was also lower in the observation group compared to S-1 (HR 0.80, 0.61-1.04, two-sided p=0.088). A total of 150 of 207 (72%) in the S-1 group completed treatment. In the safety analysis, the most common grade 3-4 adverse events in the S-1 group were neutropenia (14%) and biliary tract infection (7%). Other common adverse events were anemia, decreased platelet counts, hypoalbuminemia, and increased liver enzymes.

Image: PD

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