Originally published as JCO Early Release 10.1200/JCO.2005.07.100 on July 11 2005

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Phase I Trial of Systemic Oxaliplatin Combination Chemotherapy With Hepatic Arterial Infusion in Patients With Unresectable Liver Metastases From Colorectal Cancer

From the Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY

Address reprint requests to Nancy E. Kemeny, MD, Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; e-mail: kemenyn{at}mskcc.org

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 x 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.

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

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