| Autor: |
Bardakji, Z, Jolivet, J, Langelier, Y, Besner, J G, Ayoub, J |
| Předmět: |
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| Zdroj: |
Cancer Chemotherapy & Pharmacology; Jan1986, Vol. 18 Issue 2, p140-144, 5p |
| Abstrakt: |
We have investigated the role of metronidazole (MND) combined with 5-fluorouracil (5-FU) in the treatment of metastatic colorectal cancer. MND (750 mg/m2) was administered i.v. 1 h before 5-FU (600 mg/m2) i.v., daily for 5 consecutive days. Treatment was repeated every 4 weeks until disease progression or prohibitive toxicity occurred. Of the 27 patients entered in the study, 4 (15%) had an objective complete or partial response lasting an average of 7 months. 5-FU toxicity was greatly enhanced by the administration of MND, however, 74% of patients having granulocytopenia (less than 1500/microliter). We investigated the possible mechanisms underlying this enhanced 5-FU toxicity by examining whether MND modified 5-FU pharmacokinetics or whether the two drugs had a synergistic effect in vitro against the HCT-8 colon cancer cell line. While the in vitro studies failed to reveal any synergism between 5-FU and MND, pharmacokinetic evaluation revealed that 5-FU clearance was significantly reduced (26.9%, P less than 0.001) by prior MND administration. MND reduces 5-FU's therapeutic index in the treatment of colorectal cancer by impairing its clearance, which leads to increased toxicity without enhanced therapeutic efficacy. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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