Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer.

Abstract

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/m(2), CPT-11 150 mg/m(2), and FUDR 0.12 mg/kg x 30 mL divided by pump flow rate. The MTD for group B was Oxal 100 mg/m(2), LV 400 mg/m(2), and FU 1,400 mg/m(2) 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: Nancy Kemeny, William Jarnagin, Philip Paty, Mithat Gönen, Lawrence Schwartz, Meroë Morse, Gregory Leonard, Michael D'Angelica, Ronald DeMatteo, Leslie Blumgart, Yuman Fong
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 23 Issue 22 Pg. 4888-96 (Aug 01 2005) ISSN: 0732-183X [Print] United States
• PMID: 16009951 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article)

Chemical References

• Organoplatinum Compounds
• Oxaliplatin
• Irinotecan
• Leucovorin
• Fluorouracil
• Camptothecin

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Camptothecin (administration & dosage, analogs & derivatives)
• Colorectal Neoplasms (pathology)
• Female
• Fluorouracil (administration & dosage)
• Hepatic Artery
• Humans
• Infusions, Intra-Arterial
• Infusions, Intravenous
• Irinotecan
• Leucovorin (administration & dosage)
• Liver Neoplasms (drug therapy, secondary)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Organoplatinum Compounds (administration & dosage, adverse effects, therapeutic use)
• Oxaliplatin
• Survival Analysis
• Treatment Outcome