Irinotecan hepatic arterial infusion chemotherapy for hepatic metastases from colorectal cancer: results of a phase I clinical study.
BACKGROUND
Hepatic arterial infusion chemotherapy is a promising approach in liver metastases from colorectal cancer, but chemical hepatitis, biliary sclerosis, arterial thrombosis and right upper quadrant pain are limiting factors. Irinotecan (CPT-11) is an active drug in colorectal cancer. We planned a short hepatic arterial infusion of CPT-11 to describe the toxicity, to determine the dose-limiting toxicity, and to define the doses of CPT-11 to be recommended for phase II studies.


METHODS
Fourteen patients with a median liver substitution of 30% (10-60%) were enrolled. All patients received hepatic arterial infusion chemotherapy with CPT-11 on an outpatient basis every 3 weeks as a short, 30-min infusion.


RESULTS
At 240 mg/m2, 2 of 4 patients experienced grade 4 diarrhea and neutropenia, and 3 of them also reported grade 4 abdominal pain of the right upper quadrant. The maximum tolerated dose was reached at 240 mg/m2. The recommended doses of CPT-11 for phase II studies is 200 mg/m2, given every 3 weeks.


CONCLUSIONS
CPT-11 presents a low hepatic toxic profile and could be considered a new active drug, suitable for hepatic arterial infusion in liver metastases from colorectal cancer.
Fiorentini
G
G
Department of Oncology and Hematology, City Hospital S Maria delle Croci, Ravenna, Italy. oncologia@ra.nettuno.it
Lucchi
S R
SR
Giovanis
P
P
Cantore
M
M
Guadagni
S
S
Papiani
G
G
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects*; D002166:Camptothecin / Q000008:administration & dosage* / Q000009:adverse effects* / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D000077146:Irinotecan; D008099:Liver / Q000187:drug effects*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D059004:Topoisomerase I Inhibitors; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D000077146:Irinotecan; D002166:Camptothecin