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


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.


CONCLUSIONS
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.
Kemeny
Nancy
N
Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. kemenyn@mskcc.org
Jarnagin
William
W
Paty
Philip
P
Gönen
Mithat
M
Schwartz
Lawrence
L
Morse
Meroë
M
Leonard
Gregory
G
D'Angelica
Michael
M
DeMatteo
Ronald
R
Blumgart
Leslie
L
Fong
Yuman
Y
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D000077150:Oxaliplatin; D016019:Survival Analysis; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin