Protection by WR-2721 of the toxicity induced by the combination of cisplatin and 5-fluorouracil
| Autor: | J.A.M. van Laar, G.J. Peters, W.J.F. van der Vijgh, C.L. van der Wilt, F. Gyergyay, M. Treskes, H.M. Pinedo |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
inorganic chemicals
Cancer Research Metabolite Pharmacology In Vitro Techniques chemistry.chemical_compound Mice Amifostine Antineoplastic Combined Chemotherapy Protocols medicine Tumor Cells Cultured Animals Humans Radiology Nuclear Medicine and imaging neoplasms Cisplatin Mice Inbred BALB C Radiation Leukopenia business.industry Neoplasms Experimental Hypothermia female genital diseases and pregnancy complications Mice Inbred C57BL Oncology chemistry Cell culture Fluorouracil Toxicity Immunology Female Growth inhibition medicine.symptom business Neoplasm Transplantation medicine.drug |
| Zdroj: | International journal of radiation oncology, biology, physics. 22(4) |
| ISSN: | 0360-3016 |
| Popis: | We evaluated the effects of WR-2721 and its metabolite WR-1065 on in vitro growth inhibition by 5-fluorouracil (5FU) and cisplatin (CDDP) and the effect of WR-2721 on in vivo toxicity and antitumor effect of 5FU and CDDP. In cell culture both WR-2721 and WR-1065 were not able to reverse growth inhibition caused by either 5FU or CDDP. Administration of WR-2721 i.p. at 525 mg/kg to mice resulted in a severe temperature drop to 27°C; at 200 mg/kg hypothermia was less severe. WR-2721 failed to prevent 5FU toxicity, but the maximum tolerated dose of CDDP in the combination with 5FU (at 100 mg/kg) could be increased from 3 to 7 mg/kg. CDDP at 7 mg/kg enhanced leukopenia caused by 5FU at 100 mg/kg to 20% and thrombocytopenia to 40%; WR-2721 reduced leukopenia and prevented thrombocytopenia induced by the combination. Combination of CDDP, 5FU, and WR-2721 resulted in an enhanced antitumor activity against the murine colon tumor Colon 26 compared to 5FU alone and to 5FU combined with CDDP at their maximum tolerated dose. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|