A Study of Carboplatin–Coated Tube for the Unresectable Cholangiocarcinoma

Abstract

Most cases of cholangiocarcinoma have reached an unresectable stage by the time they are discovered despite significant progress of diagnostic modalities. Many of these patients with obstructive jaundice are often treated by biliary drainage using stents to relieve the jaundice. However, the stent patency period is as short as 3 to 9 months because of tumor ingrowth or overgrowth, and mean survival is at most 12 months. Therefore, both continuous relief of obstructive jaundice and local control of the tumor are required in the treatment for advanced cholangiocarcinoma. In this investigation, we developed a new percutaneous transhepatic biliary drainage tube coated with carboplatin (carboplatin-coated tube; CCT). CCT continuously released a fixed amount of carboplatin for 4 weeks and showed an antitumor effect on human cholangiocarcinoma cell line HuCC-T1 in vitro. When CCT was embedded in subcutaneous tumor inoculated in nude mice, a significant reduction of tumor size with no apparent damage to normal adjacent tissue was observed. On the basis of these studies, 5 patients with inoperable cholangiocarcinoma were treated with CCT for 4 weeks. Overall efficacy rate of 5 patients with cholangiocarcinoma was 60% (partial response in 3 and no change in 2). No apparent side effect was observed in these patients. Thus, CCT may provide a new treatment modality for this disease. Randomized controlled trials comparing CCT therapy with palliative stenting are required to confirm these results. (HEPATOLOGY 2000;32:916-923.)

Diagnosis and initial management of cholangiocarcinoma with obstructive jaundice

“…Biliary stent placement combined with local tumor therapy, such as brachytherapy, extra-radiation therapy, or arterial infusion chemotherapy, can prolong the survival time of patients with malignant biliary obstruction [65][66][67][68] . Mezawa et al [69] developed a new PTBD tube coated with carboplatin.…”

Cholangiocarcinoma: Molecular targeting strategies for chemoprevention and therapy

“…Another relatively recent and novel approach to palliation of unresectable cholangiocarcinoma involves the use of carboplatin-impregnated plastic biliary stents as a means of delivering cytotoxic chemotherapy directly to the tumor tissue. 10 This approach is interesting, but it also is limited by the fact that it is only effective against local and not disseminated tumor. Last, liver transplantation is not generally indicated for cholangiocarcinoma, in large part because of the high tumor recurrence rates, although a small, selected group of patients with early-stage disease have benefited from this procedure.…”

Drug-eluting/biodegradable stents

“…36 In vitro and in vivo studies (the latter using drug-coated SEMSs) have demonstrated that local exposure to paclitaxel, 5-fluorouracil, and gemcitabine can induce local responses when placed in contact with both benign and malignant GI tract tissues. [37][38][39][40][41][42][43][44] To date, there are only a few small published case series in humans. These demonstrated that partial responses in unresectable cholangiocarcinoma can be achieved with a carboplatincoated percutaneous biliary tube, 45 and endoscopically placed drug-eluting SEMS may be associated with improved stent patency and overall survival in patients with extrahepatic cholangiocarcinoma.…”