title: Hepatic arterial infusion of the nitrosourea derivate fotemustine for the treatment of liver metastases from colorectal carcinoma.
abstract: The chloroethylnitrosourea derivate diethyl-1-(3-(2-chloroethyl)-3-nitroso-ureido)-ethyl phosphonate fotemustine (FM) was investigated in a open monocentric clinical-pharmacological trial. Seventeen patients, with a median age of 57 years and progressive hepatic metastases from colorectal carcinoma received regional treatment with a stepwise dose-escalated regimen of FM to define the maximally tolerated dose. Thrombo- and leukocytopenia were dose-limiting with median nadir at day 29 (range, 19-79) and day 39 (range, 19-78), respectively. Local side-effects in the liver were mild with only transiently elevated enzymes. No other severe side-effects, except pain (WHO grade III) in one patient after the infusion of FM was noted. The maximally tolerated dose was 125 mg/m(2)/day. Plasma profiles followed a mono-exponential law (one-compartment-model). Systemic concentrations measured as area under the time-concentration curve (AUG) indicated a short plasma half-life (t(1/2)=25.8+/-11.5 min) and a high body clearance (C-L=2.193+/-870 ml/min) with large inter- and intra-individual variations. Of fifteen evaluable patients examined with CT-scan, one complete, three partial, one minor response and seven patients with stable disease were observed [ORR=27%, IC95% (4.5-49.5%)]. In summary, hepatic arterial infusion of FM appears to be effective treatment for liver metastases from colorectal carcinoma. Considering the absence of mucositis/diarrhea and hepatic toxicity, FM could be explored as an alternative to 5-FUDR or 5-FU in previously untreated patients with isolated liver metastases.
authors: UNIV HANNOVER,SCH MED,DEPT HEMATOL & ONCOL,D-30625 HANNOVER,GERMANY. INST RECH INT SERVIER,F-92415 COURBEVOIE,FRANCE. CTR RENE GAUDUCHEAU,F-44800 ST HERBLAIN,FRANCE.
authors: J
authors: J
authors: Hartmann
authors: E
authors: E
authors: Schmoll
authors: C
authors: C
authors: Bokemeyer
authors: R
authors: R
authors: Fety
authors: C
authors: C
authors: Lucas
authors: L
authors: L
authors: Dagay
authors: H
authors: H
authors: Schmoll