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

Authors: Kemeny, N.; Jarnagin, W.; Paty, P.; Gonen, M.; Schwartz, L.; Morse, M.; Leonard, G.; D'Angelica, M.; DeMatteo, R.; Blumgart, L.; Fong, Y.
Article Title: 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/m2, and FUDR 0.12 mg/kg × 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. © 2005 by American Society of Clinical Oncology.
Keywords: adult; cancer survival; clinical article; controlled study; treatment response; aged; clinical trial; disease course; neutropenia; fluorouracil; cancer combination chemotherapy; diarrhea; drug withdrawal; side effect; neurotoxicity; colorectal cancer; controlled clinical trial; thrombocytopenia; dexamethasone; irinotecan; aspartate aminotransferase blood level; drug dose escalation; febrile neutropenia; syncope; liver metastasis; folinic acid; drug infusion; liver resection; alkaline phosphatase blood level; maximum tolerated dose; phase 1 clinical trial; drug dose increase; oxaliplatin; floxuridine; bilirubin blood level
Journal Title: Journal of Clinical Oncology
Volume: 23
Issue: 22
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2005-08-01
Start Page: 4888
End Page: 4896
Language: English
DOI: 10.1200/jco.2005.07.100
PROVIDER: scopus
PUBMED: 16009951
Notes: --- - "Cited By (since 1996): 111" - "Export Date: 24 October 2012" - "CODEN: JCOND" - "Source: Scopus"
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MSK Authors
  1. Gregory David Leonard
    14 Leonard
  2. Philip B Paty
    373 Paty
  3. Leslie H Blumgart
    343 Blumgart
  4. Ronald P DeMatteo
    602 DeMatteo
  5. Mithat Gonen
    716 Gonen
  6. Lawrence H Schwartz
    281 Schwartz
  7. William R Jarnagin
    596 Jarnagin
  8. Yuman Fong
    745 Fong
  9. Nancy Kemeny
    358 Kemeny
  10. Meroe Morse
    2 Morse