Search

BACKGROUND: The standard of care for unresectable intrahepatic cholangiocarcinoma (ICC) is palliative systemic chemotherapy with cisplatin and gemcitabine. The use of hepatic arterial infusion (HAI) floxuridine (FUDR) with systemic chemotherapy may improve outcomes. We conducted a phase 1 study of HAI FUDR with systemic gemcitabine and oxaliplatin. METHODS: We enrolled patients in three cohorts: FUDR 0.16 mg/kg/day ×14 days (Cohort 1), FUDR 0.12 mg/kg/day ×14 days with gemcitabine 1,000 mg/m(2) on days 1, 8, 15 (Cohort 2), and FUDR 0.10 mg/kg/day ×14 days with gemcitabine 800 mg/m(2) days 1, 15 and oxaliplatin 85 mg/m(2) days 1, 15 (Cohort 3). The primary endpoint was the recommended phase 2 dose (RP2D). Dose limiting toxicities (DLTs) were assessed during cycle 1. Secondary objectives were response rate and survival. RESULTS: We enrolled 24 patients, 6 male, age range 42–81 years (median 64). No DLTs were observed in Cohort 1. In Cohort 2, the addition of gemcitabine 1,000 mg/m(2) days 1, 8, 15 resulted in grade 3 LFT elevation in 2 patients; for subsequent patients, the gemcitabine dose was reduced to 800 mg/m(2). No DLT were observed in Cohort 3. Most patients experienced stable disease (SD) or partial response (PR). Conversion to resectable disease occurred in all cohorts. CONCLUSIONS: Administration of FUDR via HAI pump in combination with systemic gemcitabine and oxaliplatin is well-tolerated in patients with unresectable cholangiocarcinoma. Preliminary analysis suggests a high rate of response and disease control, with some patients proceeding to resection. Based on Cohort 3, the RP2D is FUDR 0.10 mg/kg/day ×14 days, with gemcitabine 800 mg/m(2) days 1, 15 and oxaliplatin 85 mg/m(2) days 1, 15 for future studies. Future studies of this promising regimen will utilize this dosing schedule.

e16542Background: Germ cell tumor (GCT) is the most common cancer effecting males aged 15 to 35. With the implementation of cisplatin-based chemotherapy and/or surgery, the cure rate in early-stage...

746 Background: Peritoneal carcinomatosis (PC) is the intraperitoneal spread of cancer. Optimal treatment for PC is controversial. Systemic chemotherapy offers limited benefit (Franko, 2011). Intraperitoneal (IP) chemotherapy following cytoreductive surgery (CRS) improves outcomes (Verwaal, 2008). Oxaliplatin (Ox), capecitabine, and bevacizumab are standard agents for the treatment of metastatic colorectal cancer (CRC). Evidence suggests benefit of IP Ox at high doses. However, the optimal dose of IP Ox combined with standard systemic therapy is unclear. Methods: We conducted an IRB-approved phase I dose-escalation study of IP Ox D1 at 25mg/m2-100mg/m2, with systemic bevacizumab D1 at 5mg/kg, and capecitabine 850mg/m2 BID for 7 days (cycle = 14 days), in patients with PC from appendiceal or CRC after CRS. The primary aim was to determine the recommended phase II dose (RP2D)/maximum tolerated dose (MTD) for this regimen. Dose limiting toxicities (DLTs) were assessed during cycle 1. DLTs included grade 3 or 4 non-hematological toxicities, or grade 4 hematological toxicities. Results: 18 patients (12 females, median age 56) were enrolled on the study. No DLTs were observed during cycle 1 in the first 4 cohorts. One DLT (abdominal pain) was observed in cohort 5. Another patient in cohort 5 experienced grade 3 abdominal pain soon after cycle 2, thus limiting repeated treatment for this cohort. Other toxicities included fatigue (72%), nausea (61%), peripheral neuropathy (50%), constipation (50%), mucositis (39%) and dizziness (39%). See table below for average # of cycles per cohort and responses. Conclusions: IP Ox combined with capecitabine and bevacizumab is feasible. Our recommended dose for IP Ox is 85 mg/m2 with systemic therapy (cohort 4). An expansion cohort is underway for this dose level. Based on these data, further investigation of IP Ox with systemic chemotherapy for PC is warranted. Clinical trial information: NCT01061515. [Table: see text]