A Phase I Study of Adjuvant Chemotherapy With GC in Biliary Tract Cancer Undergoing Resection Without Major Hepatectomy

• Maximum tolerated dose [ Time Frame: Within 2 courses (every 2 weeks in Level -2 and -1; every 3 weeks in Level 0 and 1) ] [ Designated as safety issue: Yes ]
  To establish the maximum tolerated dose of gemcitabine plus cisplatin in patients with biliary tract cancer undergoing curative resection without major hepatectomy
  
  

• Number of Participants with dose limiting toxicity [ Time Frame: At the end of adjuvant chemotherapy (6 months) ] [ Designated as safety issue: Yes ]

  Dose limiting toxicity is defined as follows

  1. Grade 4 neutropenia, thrombocytopenia
  2. Grade 3 or 4 febrile neutropenia
  3. Grade 3 or 4 non-hematological adverse events unless unresponsive to treatment
  4. Any adverse events resulting in interruption of dosing on day 8 in both the two courses
  5. Any adverse events resulting in dose modification or delay of longer than 2 week
  
  

Surgery currently remains the only potentially curative treatment for biliary tract cancer (BTC), and most patients develop recurrence. Therefore, effective adjuvant chemotherapy is required to increase the curability of surgery and to prolong the survival in these patients. However, to date, no standard adjuvant chemotherapy has been established, and a guideline for BTC treatment recommends that trials of adjuvant chemotherapy be carried out.

Based on results from clinical studies in unresectable BTC, gemcitabine, platinum agent, fluoropyrimidine are considered to have activity against BTC. These agents are expected to be effective in the postoperative adjuvant therapy for BTC, Thus, randomized controlled trials with gemcitabine are ongoing, and the results are expected. Recently, in the ABC-02 study, the first prospective multicenter phase III study in patients with unresectable BTC, gemcitabine/cisplatin combination chemotherapy was compared with gemcitabine monotherapy and showed that the combination therapy significantly prolonged MST (from 8.1 to 11.7 months; P < 0.001). Gemcitabine/cisplatin combination therapy is now considered to be the standard regimen for unresectable BTC, and we expect this regimen to be effective for postoperative adjuvant therapy.

Though hepatectomy is frequently performed in surgery for BTC, it is unclear that the effect of anticancer agent is affected by hepatectomy. Because gemcitabine is metabolized by cytidine deaminase primarily in the liver, it considered to have decreased the metabolic ability of gemcitabine after hepatectomy. Some clinical studies demonstrated that patient with hepatectomy could not tolerate the standard dose and schedule of gemcitabine. In the adjuvant chemotherapy with gemcitabine, it is necessary to examine separately whether hepatectomy was undergone or not.

In this study, we aimed to assess the safety and efficacy of gemcitabine/cisplatin combination chemotherapy in patients with biliary tract cancer undergoing curative resection without hepatectomy.