Comparison of 4-Weekly vs 3-Weekly Gemcitabine as Adjuvant Chemotherapy Following Curative Resection for Biliary Tract Cancer: A Prospective Randomized Controlled Trial

Abstract

Background: Surgery for biliary tract cancer, including pancreatoduodenectomy and major hepatectomy, is too aggressive and does not allow postoperative gemcitabine to be administered by the usual dosage protocol. We hypothesized that the feasibility of 3-weekly protocol (days 1 and 8, every 3 weeks) of adjuvant gemcitabine therapy may be superior to the usual 4-weekly protocol (days 1, 8, and 15 every 4 weeks). Method: We compared the outcomes of 6 cycles of the 4-weekly protocol and 9 cycles of the 3-weekly protocol in a prospective randomized setting. The primary endpoint was the completion rate, and the secondary endpoints were the adverse events and the recurrence-free survival rate. Results: Totally, 27 patients were enrolled. The protocol could be completed without any omittances and/or dose modifications in two patients (14%) of the 4-weekly protocol, and three patients (23%) of the 3-weekly protocol (p = 0.8099); grade 3/4 neutropenia occurred in almost all the remaining (70%) patients. The relative dose intensity was 72% in the 4-weekly protocol and 78% in the 3-weekly protocol. There was no significant difference in the recurrence-free survival rate. Conclusion: The 3-weekly protocol did not yield superior completion, adverse events or recurrence-free survival rates as compared to the 4-week protocol. Trial Registration: UMIN-CTR, UMIN000001020.

Feasibility and efficacy of gemcitabine plus cisplatin combination therapy after curative resection for biliary tract cancer

“…The RDI of gemcitabine was 77%, which was lower than that (86%) in the CONKO-001 study conducted in patients with pancreatic cancer [10], but was similar to that (75%) in a previous study conducted in patients with BTC [11]. Considering the final completion rate was 72% in our study, which was beyond the minimum tolerable rate of 66% defined before starting this study, we regarded this regimen as feasible in the adjuvant setting in patients who underwent curative resection with or without major hepatectomy.…”

Prognostic impact of tumoral and/or peri-tumoral stromal SPARC expressions after surgery in patients with biliary tract cancer

“…Tumoral and stromal SPARC expressions were examined for associations with major clinico‐pathological parameters—including previously reported prognostic factors, such as residual tumor , pathological lymph node metastasis , invasion into nervous system , vascular invasion ,histological diagnosis (e.g., poorly differentiated tubular adenocarcinoma) , and adjuvant therapy . No analyzed factor was related to tumoral positive reactivity for SPARC (Table ).…”

Resectable Cholangiocarcinoma: Reviewing the Role of Adjuvant Strategies

“…Their study enrolled 27 patients, and the authors concluded that the three-weekly protocol did not yield superior completion as the rate of adverse events or recurrence-free survival was similar to the four-week regimen. 45 The study by Kainuma et al assessed the feasibility and the efficacy of gemcitabine plus cisplatin (CDDP) for biliary tract cancer in the adjuvant setting. Gemcitabine at 1,000 and 25 mg/m 2 of CDDP on days 1 and 8 was repeated for every three weeks.…”

“…Their study enrolled 27 patients, and the authors concluded that the three-weekly protocol did not yield superior completion as the rate of adverse events or recurrence-free survival was similar to the four-week regimen. 45…”