Pilot study of hepatic arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for patients with postoperative liver metastases from pancreatic cancer

Abstract

Abstract. hepatic metastasis is a common cause of treatment failure after curative resection of pancreatic cancer. We report a pilot study of hepatic arterial infusion (hai) chemotherapy with gemcitabine and 5-fluorouracil (5-FU) for postoperative liver metastases from pancreatic cancer. Five patients who had undergone curative resection of liver metastases from pancreatic cancer received HAI of gemcitabine and 5-FU between October 2008 and September 2010 at Kanazawa university hospital. Gemcitabine at a dose of 800 mg was infused over 30 min via a bedside pump. after gemcitabine administration, 250 mg of 5-FU was infused continuously over 24 h on days 1-5, comprising one cycle of therapy. these treatment cycles were continued biweekly. in the evaluation according to rEciSt criteria, a partial response was obtained in 2 of the 5 cases, with stable disease being achieved in the remaining 3 cases (response rate, 100%). In 4 of the 5 cases, a decrease in serum tumor marker ca19-9 was observed after 10 hai treatment cycles. the median time to treatment failure was 10 months (range 3-17). as to adverse events, leukocytopenia was grade 3 in 1 of 4 affected cases and all 5 were anemic, although 4 of the 5 cases had anemia prior to HAI therapy. Grade 2 thrombocytopenia was observed in 2 cases. no nonhematologic events, such as nausea, diarrhea, liver injury and neuropathy, occurred. there were no life-threatening toxicities, but 4 cases (80%) developed catheter complications, and the hai catheter and subcutaneous implantable port system had to be removed. hai delivers high doses of chemotherapeutic agents directly into tumor vessels, producing increased regional levels with greater efficacy and a lower incidence/ severity of systemic side effects. in conclusion, hai chemotherapy is useful and safe for the treatment of malignancies confined to the liver. Introductionpancreatic cancer is one of the major causes of cancer-related death globally, with a 5-year survival rate of less than 5% (1,2). For patients with localized disease, radical surgery may provide long-term benefits. However, even in patients who undergo resection, the reported 5-year survival rate remains in the range of 7-24%, and median survival is only approximately 1 year in most series, indicating that surgery alone is generally inadequate. Even after curative resection, patients with pancreatic cancer face a 50-80% local recurrence rate and a 25-50% chance of developing distant metastases (3).Gemcitabine, a deoxycytidine analogue that competes for incorporation into dna thereby inhibiting its synthesis, is the key drug employed in the treatment of pancreatic cancer. adjuvant chemotherapy with gemcitabine improves, although to a limited degree, the survival of patients with resectable pancreatic adenocarcinoma as compared to resection alone (4). however, a major drawback of adjuvant therapy for pancreatic cancer is that 20-30% of patients cannot receive the designated therapy as a result of postoperative complications, delayed surgical recovery and/or ear...

Saturable Hepatic Extraction of Gemcitabine Involves Biphasic Uptake Mediated by Nucleoside Transporters Equilibrative Nucleoside Transporter 1 and 2

“…These results indicate that the low‐affinity site is the main contributor to GEM uptake at this concentration. These results are consistent with the fact that severe adverse events, especially events related to bone‐marrow suppression, were not observed in our phase I clinical study of HAI (dose: 800 mg/SLV) . Indeed, it may be possible to increase the dose of GEM in HAI to achieve a greater therapeutic effect without adverse effects.…”

“…15 As GEM is mainly eliminated by hepatic metabolism (the renal excretion rate of unchanged GEM is less than 10%) and shows a high hepatic extraction rate, 13 it is a good candidate for administration by HAI. Indeed, we and other researchers [16][17][18] have reported that the systemic concentration of GEM after administration by HAI is lower than that after i.v. administration.…”

“…We have also reported that administration of 400 mg GEM/body for 30 min by HAI did not lead to severe adverse events in patients with postoperative liver metastases from pancreatic cancer, 19 and we confirmed the effectiveness and safety of GEM HAI. [18][19][20][21] The response rate according to the response evaluation criteria in solid tumors was 80%-100%, and severe adverse events, especially leukocytopenia and thrombocytopenia, were not encountered.…”

Hepatic arterial infusion chemotherapy with gemcitabine and 5-fluorouracil or oral S-1 improves the prognosis of patients with postoperative liver metastases from pancreatic cancer

“…The flow volume of the hepatic artery proper is reportedly ~330 ml/min (11). When an 800-mg dose of GEM is infused into the hepatic artery proper over a 30-min period, the local plasma concentration in the liver reaches ~80,000 ng/ml by 30 min.…”

Multiple liver metastases of pancreatic solid pseudopapillary tumor treated with resection following chemotherapy and transcatheter arterial embolization: A case report

“…In October 2011, oral S-1 (80 mg/m 2 ) and HAI with GEM (1,000 mg/standard liver volume) were initiated as described in a previous report (7). Following 18 cycles of HAI chemotherapy, the tumors exhibited a 26.3% reduction in size (Fig.…”