In vivo evidence of complete circumvention of vincristine resistance by a new triazinoaminopiperidine derivative S 9788 in P388/VCR leukemia model

• Published in: Cancer chemotherapy and pharmacology 1992, Vol.30 (6), p.491-494
• Main Authors: Cros, S, Guilbaud, N, Berlion, M, Dunn, T, Regnier, G, Dhainaut, A, Atassi, G, Bizzari, J P
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation, Preclinical; Drug Resistance - genetics; Female; Leukemia P388 - drug therapy; Leukemia P388 - genetics; Mice; Mice, Inbred Strains; Piperidines - administration & dosage; Piperidines - pharmacology; Triazines - administration & dosage; Triazines - pharmacology; Vincristine - administration & dosage; Vincristine - therapeutic use
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/BF00685604

S 9788, a new triazinoaminopiperidine derivative, was found to be a potent reversant of vincristine resistance in the in vivo murine leukemic P388/VCR model. In two treatment regimens (Q4D days 1, 5 and 9 and QD days 1-9), S 9788 enhanced the antitumor activity of vincristine in a dose-dependent manner, resulting in a complete circumvention of drug resistance for well-tolerated doses of S 9788. S 9788 was also effective in enhancing therapeutic effects of vincristine in the treatment of sensitive P388-bearing mice. These results strongly suggest that S 9788 may be a potential candidate for circumvention of multidrug resistance (MDR) in clinical practice.