| Autor: |
Hartmann J; 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., Schmoll E, Bokemeyer C, Fety R, Lucas C, Dagay L, Schmoll H |
| Jazyk: |
angličtina |
| Zdroj: |
Oncology reports [Oncol Rep] 1997 Jan-Feb; Vol. 4 (1), pp. 167-72. |
| DOI: |
10.3892/or.4.1.167 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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