title: Systemic irinotecan or regional floxuridine chemotherapy prolongs survival after hepatic cryosurgery in patients with metastatic colon cancer refractory to 5-fluorouracil.
abstract: Most colorectal cancers metastatic to the liver are resistant to chemotherapy and are not amenable to surgical resection. This study evaluated our 6-year experience (July 1992-July 1998) in treating patients with unresectable hepatic colorectal metastases refractory to systemic 5-fluorouracil (5-FU). One hundred fifty-three patients underwent cryosurgical ablation (CSA) of 5-FU-resistant hepatic metastases. The patients then received either hepatic arterial floxuridine (FUDR), systemic CPT-11, or no postoperative adjuvant chemotherapy. Number, size, and location of hepatic metastases, carcinoembryonic antigen (CEA) levels, and type of postoperative treatment were analyzed. One to 15 lesions were frozen (median number, 3; median size, 6 cm), for a total of 73 synchronous and 80 metachronous lesions. Overall median survival was 28.4 months from the date of diagnosis of liver metastases and 16.1 months from the time of CSA. After cryosurgery alone, median survival was 13 months, which was significantly shorter than the post-CSA survival of 23.6 months with adjuvant CPT-11 and 21.2 months with hepatic FUDR (P = 0.007). Predictors of survival included preoperative CEA, postoperative reduction in CEA, and adjuvant chemotherapy (P < 0.05). Neither size, number of lesions, nor tumor location impacted survival. At a median follow-up of 13 months, 67% of patients have recurred (35% hepatic, 16% extrahepatic, and 49% both). Twenty percent of the recurrences were in the lobe of the CSA site. The 25 patients who underwent a second CSA had a median survival of 28.4 months from CSA and 40 months from the date of diagnosis of liver metastases. These data indicate that CSA offers an effective alternative for unresectable patients resistant to 5-FU. Systemic CPT-11 or regional FUDR may further prolong survival after CSA.
authors.affiliation: John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA, USA. BilchikA@jwci.org
authors.forename: A J
authors.initials: AJ
authors.lastname: Bilchik
authors.forename: T F
authors.initials: TF
authors.lastname: Wood
authors.forename: S P
authors.initials: SP
authors.lastname: Chawla
authors.forename: D M
authors.initials: DM
authors.lastname: Rose
authors.forename: M H
authors.initials: MH
authors.lastname: Chung
authors.forename: S S
authors.initials: SS
authors.lastname: Stern
authors.forename: L J
authors.initials: LJ
authors.lastname: Foshag
authors.forename: K P
authors.initials: KP
authors.lastname: Ramming
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D017024:Chemotherapy, Adjuvant; D010478:Chemotherapy, Cancer, Regional Perfusion; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology; D003452:Cryosurgery; D018572:Disease-Free Survival; D005467:Floxuridine / Q000008:administration & dosage*; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging / Q000401:mortality; D011355:Prodrugs / Q000008:administration & dosage*; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed; D059004:Topoisomerase I Inhibitors; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D011355:Prodrugs; D059004:Topoisomerase I Inhibitors; D005467:Floxuridine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin