Hepatic arterial infusion of the nitrosourea derivate fotemustine for the treatment of liver metastases from colorectal carcinoma
| Autor: | R Fety, L DAgay, Hans-Joachim Schmoll, Joerg T. Hartmann, Carsten Bokemeyer, E Schmoll, C Lucas |
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| Rok vydání: | 2011 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Nitrosourea business.industry Colorectal cancer Cancer General Medicine medicine.disease Gastroenterology Regimen chemistry.chemical_compound Hepatic arterial infusion Leukocytopenia chemistry Internal medicine medicine Mucositis Fotemustine business medicine.drug |
| Zdroj: | Oncology reports. 4(1) |
| ISSN: | 1021-335X |
| Popis: | 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: | OpenAIRE |
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