OBJECTIVES: No established therapy exists for unresectable intrahepatic cholangiocarcinoma (ICC). We conducted a phase I/II study to ascertain the recommended dose (RD) of hepatic arterial infusion using gemcitabine (GEM) for ICC and to assess the efficacy and safety. METHODS: For patients with unresectable ICC, GEM was administered through the hepatic artery via the port system as a 30-minute infusion on days 1, 8, and 15 every 4 weeks for 5 cycles. In phase I, dosage for levels 1, 2, and 3 was set at 600, 800, and 1000 mg/m, respectively, and was increased in 3 to 6 patients at a time. Maximum tolerated dose was defined as a dosage resulting in dose-limiting toxicity in 2 of 3 patients or 3 of 6 patients, and RD was estimated during the first cycle. In the phase II, more RD patients were added to assess tumor response and toxicity. RESULTS: During the phase I, 16 patients were enrolled. Maximum tolerated dose was not reached. Assuming RD at 1000 mg/m, the phase II enrolled a total of 13 patients. The following Grade 3 toxicities were observed: neutropenia 20%, increased gamma-glutamyl transpeptidase 8%, increased aspartate aminotransferase 4%, increased alanine aminotransferase 4%, increased bilirubin 4%, nausea 4%, and fatigue 4%. The tumor response rate was 7.7% (complete response 0, partial response 1, stable disease 8, and progressive disease 4). CONCLUSION: Whereas the toxicity of hepatic arterial infusion with 1000 mg/m GEM for ICC was tolerable, expected efficacy could not be obtained, thus suggesting only minimal activity.
OBJECTIVES: No established therapy exists for unresectable intrahepatic cholangiocarcinoma (ICC). We conducted a phase I/II study to ascertain the recommended dose (RD) of hepatic arterial infusion using gemcitabine (GEM) for ICC and to assess the efficacy and safety. METHODS: For patients with unresectable ICC, GEM was administered through the hepatic artery via the port system as a 30-minute infusion on days 1, 8, and 15 every 4 weeks for 5 cycles. In phase I, dosage for levels 1, 2, and 3 was set at 600, 800, and 1000 mg/m, respectively, and was increased in 3 to 6 patients at a time. Maximum tolerated dose was defined as a dosage resulting in dose-limiting toxicity in 2 of 3 patients or 3 of 6 patients, and RD was estimated during the first cycle. In the phase II, more RD patients were added to assess tumor response and toxicity. RESULTS: During the phase I, 16 patients were enrolled. Maximum tolerated dose was not reached. Assuming RD at 1000 mg/m, the phase II enrolled a total of 13 patients. The following Grade 3 toxicities were observed: neutropenia 20%, increased gamma-glutamyl transpeptidase 8%, increased aspartate aminotransferase 4%, increased alanine aminotransferase 4%, increased bilirubin 4%, nausea 4%, and fatigue 4%. The tumor response rate was 7.7% (complete response 0, partial response 1, stable disease 8, and progressive disease 4). CONCLUSION: Whereas the toxicity of hepatic arterial infusion with 1000 mg/m GEM for ICC was tolerable, expected efficacy could not be obtained, thus suggesting only minimal activity.
Authors: Ioannis T Konstantinidis; Bas Groot Koerkamp; Richard K G Do; Mithat Gönen; Yuman Fong; Peter J Allen; Michael I D'Angelica; T Peter Kingham; Ronald P DeMatteo; David S Klimstra; Nancy E Kemeny; William R Jarnagin Journal: Cancer Date: 2015-12-22 Impact factor: 6.860
Authors: Anna Maria Ierardi; Salvatore Alessio Angileri; Francesca Patella; Silvia Panella; Natalie Lucchina; Elena N Petre; Antonio Pinto; Giuseppe Franceschelli; Gianpaolo Carrafiello; Gianpaolo Cornalba; Constantinos T Sofocleous Journal: Med Oncol Date: 2016-12-22 Impact factor: 3.064
Authors: M Sinn; A Nicolaou; B Gebauer; P Podrabsky; D Seehofer; J Ricke; B Dörken; H Riess; B Hildebrandt Journal: Dig Dis Sci Date: 2013-03-24 Impact factor: 3.199