Early Relapse of Unresectable Gallbladder Cancer after Discontinuation of Gemcitabine Monotherapy Administered for 5 Years in a Patient Who Had Complete Response to the Treatment
A 77-year-old man with a 2-month history of right shoulder and upper abdominal pain visited his physician at another hospital. A gallbladder tumor, about 3 cm in diameter, was detected by ultrasonography, and the patient was then referred to our hospital for further diagnosis and treatment. His laboratory findings at presentation were nearly normal, including the serum levels of tumor makers. Computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen showed the mass to be located at the cervix of the gallbladder and to involve the common and right hepatic arteries, with enlargement of the No. 12 lymph node (fig. ). A percutaneous biopsy of the tumor revealed an adenocarcinoma, and immunohistochemical analysis of the tumor showed positive staining for carcinoembryonic antigen (CEA) and cytokeratin 7, and negative staining for cytokeratin 20. Thus, the tumor was diagnosed as an unresectable gallbladder cancer.\nThe patient was initiated on treatment with gemcitabine at a dose of 1,000 mg/m2 administered on days 1, 8, and 15 of each 4-weekly cycle. After 13 cycles of treatment, a marked decrease of the tumor size on CT was noted (fig. ), and the treatment response was rated as partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.0. After 15 cycles of treatment, the tumor disappeared altogether, and CR was confirmed by CT after 20 cycles of gemcitabine monotherapy (fig. ). After CR had been achieved, the tumor was reevaluated for possible surgical resection by our surgeon. However, the patient was judged to be an unsuitable candidate for surgery, because he had severe bronchial asthma. Therefore, gemcitabine monotherapy was continued. After 27 cycles of treatment, corresponding to a further 12 months of treatment after CR had been confirmed, we held a discussion with the patient and his family about whether or not they would like the gemcitabine therapy to be continued. They made the decision for the gemcitabine therapy to be continued, for fear that the tumor might relapse. At this time, because of thrombocytopenia, the administration schedule of gemcitabine was changed to 3-weekly cycles, with the drug administered at the same dose as previously, but on days 1 and 8, followed by 1 week's rest. From the 40th cycle onward, the administration schedule was changed again to biweekly cycles, with no reduction of the drug dose, because of grade 1 malaise.\nAfter the completion of 5 years of treatment with gemcitabine, we again held discussions with the patient and his family and decided to discontinue the gemcitabine therapy, because the patient had remained relapse free for 45 months. Gemcitabine had been administered a total of 160 times, over 60 cycles, for 5 years, while the drug toxicities had remained rather mild in nature throughout the course of treatment, consisting only of grade 2 leukopenia and thrombocytopenia and grade 1 malaise.\nHowever, 11 months after treatment discontinuation, the patient presented with signs of obstructive jaundice. Brushing cytology of the bile duct by endoscopic retrograde cholangiopancreatography revealed an adenocarcinoma. MRI showed relapse of the tumor at the porta hepatis (fig. ). The metastases to the lymph nodes invaded the celiac artery and common hepatic artery. Thus, the patient was diagnosed as having unresectable relapse of gallbladder cancer, and gemcitabine therapy was restarted. Six months later, the tumors showed an increase in size and multiple liver metastases appeared. The second term of gemcitabine therapy was less effective against the disease as compared to the first, although the best response was stable disease. At the time this case report was written, the patient was receiving S-1 therapy and has remained alive for 79 months after the commencement of the first gemcitabine therapy. Serial changes of the serum levels of carbohydrate antigen 19-9 and CEA during the entire treatment are shown in fig. .