TY - JOUR
T1 - Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer
AU - Kemeny, Nancy
AU - Jarnagin, William
AU - Paty, Philip
AU - Gönen, Mithat
AU - Schwartz, Lawrence
AU - Morse, Meroë
AU - Leonard, Gregory
AU - D'Angelica, Michael
AU - DeMatteo, Ronald
AU - Blumgart, Leslie
AU - Fong, Yuman
PY - 2005
Y1 - 2005
N2 - Purpose: To determine the maximum-tolerated dose (MTD) of concurrent systemic oxaliplatin (Oxal) combinations plus hepatic arterial infusion (HAI) in patients with unresectable hepatic metastases from colorectal cancer. Patients and Methods: Thirty-six patients (89% previously treated) with unresectable liver metastases were treated with concurrent HAI and systemic Oxal plus irinotecan (CPT-11; group A) or Oxal, fluorouracil (FU), and leucovorin (LV; group B). Systemic chemotherapy was administered every 2 weeks concurrent with 2 weeks of HAI floxuridine (FUDR) and dexamethasone (Dex) every 28 days. Results: The MTD for patients in group A was Oxal 100 mg/m2, CPT-11 150 mg/m2, and FUDR 0.12 mg/kg × 30 mL divided by pump flow rate. The MTD for group B was Oxal 100 mg/m2, LV 400 mg/m2, and FU 1,400 mg/m2 by continuous infusion over 48 hours, with the same FUDR dose as in group A. Grade 3 or 4 toxicities in groups A and B included diarrhea (24% and 20%), neutropenia (10% and 7%), neurotoxicity (24% and 20%), and bilirubin more than 3 mg/mL (5% and 7%, respectively). The complete and partial response rate totaled 90% for group A and 87% for group B. Median survival time was 36 and 22 months for groups A and B, respectively. Seven patients in group A were ultimately able to undergo liver resection. Conclusion: Combination therapy with HAI FUDR and Dex plus systemic Oxal combinations may be safely administered to patients with colorectal cancer. The high response rate (88%) and the possibility of conversion to resectability, despite disease progression on prior systemic regimens, suggest that these combinations should be evaluated in larger studies as first- or second-line therapy in patients with hepatic metastases from colorectal cancer.
AB - Purpose: To determine the maximum-tolerated dose (MTD) of concurrent systemic oxaliplatin (Oxal) combinations plus hepatic arterial infusion (HAI) in patients with unresectable hepatic metastases from colorectal cancer. Patients and Methods: Thirty-six patients (89% previously treated) with unresectable liver metastases were treated with concurrent HAI and systemic Oxal plus irinotecan (CPT-11; group A) or Oxal, fluorouracil (FU), and leucovorin (LV; group B). Systemic chemotherapy was administered every 2 weeks concurrent with 2 weeks of HAI floxuridine (FUDR) and dexamethasone (Dex) every 28 days. Results: The MTD for patients in group A was Oxal 100 mg/m2, CPT-11 150 mg/m2, and FUDR 0.12 mg/kg × 30 mL divided by pump flow rate. The MTD for group B was Oxal 100 mg/m2, LV 400 mg/m2, and FU 1,400 mg/m2 by continuous infusion over 48 hours, with the same FUDR dose as in group A. Grade 3 or 4 toxicities in groups A and B included diarrhea (24% and 20%), neutropenia (10% and 7%), neurotoxicity (24% and 20%), and bilirubin more than 3 mg/mL (5% and 7%, respectively). The complete and partial response rate totaled 90% for group A and 87% for group B. Median survival time was 36 and 22 months for groups A and B, respectively. Seven patients in group A were ultimately able to undergo liver resection. Conclusion: Combination therapy with HAI FUDR and Dex plus systemic Oxal combinations may be safely administered to patients with colorectal cancer. The high response rate (88%) and the possibility of conversion to resectability, despite disease progression on prior systemic regimens, suggest that these combinations should be evaluated in larger studies as first- or second-line therapy in patients with hepatic metastases from colorectal cancer.
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U2 - 10.1200/JCO.2005.07.100
DO - 10.1200/JCO.2005.07.100
M3 - Article
C2 - 16009951
AN - SCOPUS:24644484863
SN - 0732-183X
VL - 23
SP - 4888
EP - 4896
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 22
ER -