title: Combined systemic chronotherapy and hepatic artery infusion for the treatment of metastatic colorectal cancer confined to the liver.
abstract: BACKGROUND
  The optimal treatment of patients with metastatic colorectal cancer is still a clinical challenge. We describe the use of combined hepatic arterial infusion (HAI) of irinotecan (CPT-11) in conjunction with systemic chronotherapy infusion of 5-fluorouracil (5FU), folinic acid and carboplatin in patients with colorectal liver metastases.
  
  
  METHODS
  Twenty-three patients with colorectal cancer and isolated liver metastases were enrolled in this trial. Intraoperative insertion of an intra-arterial catheter into the hepatic artery was accomplished during the colon operation (in cases of synchronous tumor) or as a separate procedure in colorectal cancer patients with newly diagnosed liver metastases. A systemic double-lumen double-chamber port was inserted via the subclavian vein as a separate procedure. The treatment plan included irinotecan given by intra-arterial infusion at 150 mg/m2 for 1 h. After 2 weeks of rest chronomodulated 5FU (700 mg/m(2); peak delivery rate at 04:00 h), leucovorin (175 mg/m2; peak delivery rate at 04:00 h) and carboplatin (40 mg/m2; peak delivery rate at 16:00 h) for 4 days was followed by 10 days' rest and then given again. After 10 days' rest another HAI was introduced using the same method. Each cycle of therapy included 2 HAI courses and 2 chronotherapy courses in between. After 2 complete cycles, patients were evaluated for their response with weekly accessed toxicity recording.
  
  
  RESULTS
  Seven women, 8 men, median age 61 years (range 46-72). Eight patients had synchronous colon and hepatic disease and 7 patients had metachronous disease. Ten patients had previously been treated with 5FU and leucovorin while 5 patients were chemonaive. The mean number of cycles were 11.6 per patient (range 8-19). Partial response was achieved in 6 patients (40%) and was followed by laparoscopic radiofrequency ablation in 5 patients (33%). Disease stabilization was observed in 2 patients (13%) and disease progression in 7 patients (47%) mainly after previous chemotherapy failure. Side effects were infrequent and mild including grade 2 GIT complaints (5 patients), RUQ pain during HAI (9 patients) and grade 2 hematological complaints in 2 patients.
  
  
  CONCLUSIONS
  A combined chemotherapy protocol (HAI and chronotherapy) with irinotecan (CPT-11) together with chronomodulated infusion of 5FU, folinic acid and carboplatin can be used in metastatic colorectal patients with a high efficacy rate and minor side effects especially in pretreated patients.
authors.affiliation: Department of Surgery, Wolfson Medical Center, Holon, Israel. shmoti@netvision.net.il
authors.forename: Mordechai
authors.initials: M
authors.lastname: Shimonov
authors.forename: Henry
authors.initials: H
authors.lastname: Hayat
authors.forename: Samario
authors.initials: S
authors.lastname: Chaitchik
authors.forename: Joseph
authors.initials: J
authors.lastname: Brener
authors.forename: Pinhas
authors.initials: P
authors.lastname: Schachter
authors.forename: Abraham
authors.initials: A
authors.lastname: Czerniak
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016190:Carboplatin / Q000008:administration & dosage; D019454:Chronotherapy; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007261:Infusions, Intra-Arterial; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D011788:Quality of Life
chemical_list: D000077146:Irinotecan; D016190:Carboplatin; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin