Hepatic artery infusion with 5‐fluorouracil and mitomycin‐c in metastatic colorectal carcinoma phase ii study

Abstract

Thirty-two patients with hepatic metastases colorectal carcinoma were treated with hepatic artery infusion (HAI) employing 5-fluorouracil (5-FU) and mitomycin-C (mito-C). Catheters were placed percutaneously via the femoral artery. Two schedules were employed: ( I ) 5-FU 1,200 mg/m2 IA (D1-4) and mito-C 8 mg/m2IA (D1 +D4); (2) 5-FU 1,200 mg/m2 IA (Dl-6) and mito-C 8 mg/m2 IA (D1 fD4).Courses were repeated every 4 weeks. Thirty patients with measurable disease were evaluable, 22 received schedule I and 8 patients schedule 11. Complete response occurred in two patients (6.7%) and partial response in 13 patients (43.3%). Five patients (16.7%) had minimal regression. The overall response rate was 66.7%. Median survival of all patients from start of treatment was 11.2 months. Median survival of responders and nonresponders was 12.4 months and 4.6 months, respectively (PcO.05). No differences in response rates, duration of response, or survival was seen between the two schedules. Drug toxicity was moderate to severe, but morbidity of HAI per se was minimal. Intermittent HA1 of 5-FU and mito-C is a well-tolerated treatment modality associated with few serious complications. The response rate, duration of response, and the survival is comparable to continuous HA1 infusion of 5-FU or floxuridine (FUDR). As given in this mdy, mito-C did not appear to provide added benefit.

Mitomycin C: a clinical update

“…Regional chemotherapy of metastatic colorectal cancer has been under investigation for several years (113). Hepatic arterial infusion with MMC + floxuridine (114), 5-FU + Adriamycin + MMC (FAM) (115) or 5-FU + MMC (116) have given fairly high response rates but the role of MMC is unclear. Mitomycin C alone has been used intra-arterially and given responses of 17% (117) and 20% (118).…”

Differential Tumor Regression in Patients with Bilobar Hepatic Metastases and Dual Arterial Supply: Evidence Supporting the Advantage of Intra-Arterial over Intravenous Route of Drug Delivery

“…This important recognition of the liver as a locus minoris resistentiae has catapulted immeasurably the use of hepatic arterial infusion of chemotherapy for local-regional control either through percutaneously inserted catheters or via ¡mplantable pumps (3)(4)(5)(6)(7)(8). The basic premise in support of such somewhat cumbersome therapeutic approach (as opposed to the conventional systemic IV route of drug administration) has been the notion that the higher, more effective pharmacologie concentration of some antineoplastic drugs can be achieved with similar or less myelosuppression resulting in a wider drug gradient across the tumor cell membrane and a greater tumor cell damage.…”

Regional Chemotherapy of Gastro-Intestinal Cancer

“…Additionally, in a study on 54 patients with non-resectable métastasés of colorectal [135] 1975 5-FU 83 12 Pctrck and Minton [ 136] 1979 5-FU 50 9 Theodors ct al. [137] 1982 5-FU + MMC 59 12 Weiss ct al. [138] 1983 FUDR 29 13 Denck [ 139] 1984 5-FU 58 14 Niederhuber et al [ 140] 1984 FUDR + MMC 83 18 Donegan [141] 1985 5-FU 57 15 Ekberget al [142] 1986 5-FU 36 II Metzger [143] 1986 5-FU + MMC 42 18 Thirewell ct al.…”