Gemcitabine, Cisplatin, and Durvalumab for Alpha-Fetoprotein-Producing Cancer of Unknown Primary Suspected from the Biliary Tract: A Case Report.

INTRODUCTION: Cancer of unknown primary (CUP) often presents with distant metastases, and chemotherapy remains the standard treatment. Chemotherapeutic regimens are selected based on tumor marker profiles and immunohistochemical staining of tumor cells, with the most suitable agents chosen according to the presumed primary site. Until recently, chemotherapy for biliary tract cancer has typically consisted of a combination of gemcitabine and cisplatin (CDDP). However, immune checkpoint inhibitors (ICIs) have also been introduced in recent years. CASE PRESENTATION: We report the case of a 67-year-old man who was found to have elevated serum alpha-fetoprotein (AFP) levels and enlarged lymph nodes at the hepatic on abdominal-pelvic CT. EUS-FNA/B and laparotomy biopsy of the lymph nodes confirmed a diagnosis of AFP-producing adenocarcinoma. Immunohistochemical staining demonstrated positivity for CA19-9, CK19, and CK20, suggesting a biliary tract origin. After initial chemotherapy treatment, the regimen was switched to a combination of gemcitabine, combination of gemcitabine and cisplatin, and durvalumab (GCD), and treatment was continued. Six months after initiating GCD therapy, the patient achieved a partial response on CT imaging and was transitioned to durvalumab monotherapy for maintenance. Tumor shrinkage persisted, and maintenance therapy with durvalumab alone was successfully sustained for 24 months. Following subsequent disease progression, rechallenge with GCD therapy again proved effective, and a 3-year overall survival was achieved. CONCLUSION: Although CUP generally carries a poor prognosis, GCD therapy may represent an effective option for CUP with suspected biliary tract origin.