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A phase I trial of isolated hepatic perfusion (IHP) using 5-FU and oxaliplatin in patients with unresectable isolated liver metastases from colorectal cancer.
A phase I trial of isolated hepatic perfusion (IHP) using 5-FU and oxaliplatin in patients with unresectable isolated liver metastases from colorectal cancer.
- Source :
-
Annals of surgical oncology [Ann Surg Oncol] 2013 Jul; Vol. 20 (7), pp. 2180-7. Date of Electronic Publication: 2013 Apr 11. - Publication Year :
- 2013
-
Abstract
- Background: Isolated hepatic perfusion (IHP) with melphalan is an established approach for patients with unresectable metastatic liver lesions. This study determined the safety and maximum tolerated dose (MTD) of 5-FU with oxaliplatin via IHP.<br />Methods: Standard 3 × 3 Phase I design. Subjects with unresectable isolated CRC liver metastases scheduled for HAI pump were eligible. IHP used fixed-dose oxaliplatin with escalating 5-FU doses. Toxicity (CTCAE v 4.0) and response (RECIST), progression-free survival, and overall survival (OS) were assessed. Systemic and IHP plasma PK of 5-FU, anabolites, and platinum were determined.<br />Results: All 12 patients had received ≥ 1 line of pre-IHP chemotherapy. There were 4 grade 3 serious adverse events (33.3 %) and 1 grade 4 event (8.3 %). Also, 2 dose-limiting toxicities occurred at DL2 at 300 mg/m(2), resulting in expansion of DL1 at 200 mg/m(2) 5-FU, the eventual MTD. At 6-month follow-up, 9 patients (82 %) demonstrated partial response, while 2 (18 %) exhibited stable disease. Also, 64 % of patients demonstrated a >50 % decrease in CEA. The 1- and 2-year OS probabilities were 90.9 and 71.6 %, respectively, with median follow-up of 24 months. IHP exposures (AUC0-60 min) were 10.9 ± 4.5 μgPt h/mL, 49.3 ± 30.7 μg h/mL 5-FU (DL1), and 70.5 ± 35.5 μg h/mL 5-FU (DL2). Systemic exposure (AUC0-inf) relative to IHP exposure was negligible for both platinum (1.1 ± 1.5 %) and 5-FU (0.09 ± 0.10 %).<br />Conclusions: The MTD for IHP was 200 mg/m(2) 5-FU with 40 mg/m(2) oxaliplatin. Systemic exposure to the agents was minimal during IHP. The response and survival observed warrants assessment in a larger phase II trial.
- Subjects :
- Adult
Antineoplastic Combined Chemotherapy Protocols pharmacokinetics
Area Under Curve
Carcinoembryonic Antigen blood
Colorectal Neoplasms blood
Disease-Free Survival
Female
Fluorouracil administration & dosage
Fluorouracil pharmacokinetics
Humans
Kaplan-Meier Estimate
Liver Neoplasms blood
Liver Neoplasms secondary
Male
Middle Aged
Organoplatinum Compounds administration & dosage
Organoplatinum Compounds pharmacokinetics
Oxaliplatin
Antineoplastic Combined Chemotherapy Protocols administration & dosage
Antineoplastic Combined Chemotherapy Protocols adverse effects
Chemotherapy, Cancer, Regional Perfusion adverse effects
Colorectal Neoplasms pathology
Liver Neoplasms drug therapy
Maximum Tolerated Dose
Subjects
Details
- Language :
- English
- ISSN :
- 1534-4681
- Volume :
- 20
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Annals of surgical oncology
- Publication Type :
- Academic Journal
- Accession number :
- 23575907
- Full Text :
- https://doi.org/10.1245/s10434-013-2960-3