Phase I trial of intoplicine (RP 60475) administered as a 72 h infusion every 3 weeks in patients with solid tumors

Anti-Cancer Drugs

Volumn 10, Issue 10, 1999, Pages 889-894

  Newman, Robert A ^a   Kim, Jeri ^a   Newman, Beverly M ^a   Bruno, Rene ^b   Bayssas, Martine ^b   Klink Alak, May ^b   Pazdur, Richard ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b SANOFI   (France)

Author keywords

Intoplicine; NSC 645008; Pharmacokinetics; Phase I; RP 60475

Indexed keywords

ANTINEOPLASTIC AGENT; DNA TOPOISOMERASE; DNA TOPOISOMERASE (ATP HYDROLYSING); INTOPLICINE;

ADULT; ADVANCED CANCER; AGED; ANEMIA; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BONE MARROW SUPPRESSION; CLINICAL ARTICLE; CLINICAL TRIAL; CONTINUOUS INFUSION; DRUG BLOOD LEVEL; DRUG ERYTHROCYTE LEVEL; ENZYME INHIBITION; FEMALE; GRANULOCYTOPENIA; HUMAN; LEUKOPENIA; LIVER TOXICITY; MALE; NAUSEA; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; SOLID TUMOR; THROMBOCYTOPENIA;

EID: 0033369301     PISSN: 09594973     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001813-199911000-00004     Document Type: Article

References (15)

1. Schneider E, Hsiang Y-H, Liu LF. DNA topoisomerases as anticancer drug targets. Adv Pharmacol 1990; 21: 149-83.
2. Riou J-F, Fosse P, Nguyen CH, et al. Intoplicine (RP 60475) and its derivatives, a new class of antitumor agents inhibiting both topoisomerase I and II activities. Cancer Res 1993; 53: 5987-93.
3. Morjani H, Riou J-F, Nabiev I, et al. Molecular and cellular interactions between intoplicine, DNA, and topoisomerase II studied by surface-enhanced raman scattering spectroscopy. Cancer Res 1993; 53: 4784-90.
4. Riou JF, Fosse P, Bissery MC, et al. RP60475 and, derivatives, a new class of antitumor agents inhibiting both topoisomerase I and II activities. Proc Am Ass Cancer Res 1992; 33: 437 (abstr 2611).
5. Poddevin B, Riou JF, Lavelle F, Pommier Y. Dual topoisomerase I and II inhibition by RP 60475, an intercalating agent in early clinical trial. Proc Am Ass Cancer Res 1992; 33: 437 (abstr 2612).
6. Von Hoff DD, Burris III HA, Eckardt J, et al. Preclinical and phase I trials of topoisomerase I inhibitors. Cancer Chemother Pharmacol 1994; 34: S41-5.
7. Hanauske A-R, Clark GM, Von Hoff DD. Adenocarcinoma of unknown primary: retrospective analysis of chemosensitivity of 313 fleshly explanted tumors in a tumor cloning system. Invest New Drugs 1995; 13: 43-9.
8. Eckardt JR, Burris III HA, Kuhn JG, et al. Activity of intoplicine (RP 60475), a new DNA topoisomerase I and II inhibitor, against human tumor colony-forming units in vitro. J Natl Cancer Inst 1994; 86: 30-3.
9. Poddevin B, Riou J-F, Lavelle F, et al. Dual topoisomerase I and II inhibition by intoplicine (RP-60475), a new antitumor agent in early clinical trials. Mol Pharmacol 1993; 44: 767-74.
10. Nabiev I, Chourpa I, Riou J-F, et al. Molecular interactions of DNA-topoisomerase I and II inhibitors with DNA and topoisomerases and in ternary complexes: binding modes and biological effects for intoplicine derivatives. Biochemistry 1994; 33: 9013-23.
11. Bissery M-C, Nguyen CH, Bisagni E, et al. Antitumor activity of intoplicine (RP 60475, NSC 645008), a new benzopyrido-indole: evaluation against solid tumors and leukemias in mice. Invest New Drugs 1993; 11: 263-77.
12. van Gijn R, Rosing H, ten Bokkel Huinink WW, et al. Determination of intoplicine, a new antitumor drug, in human whole blood and plasma by normal-phase high-performance liquid chromatography with fluorescence detection. J Chroromatogr 1993; 614: 299-306.
13. Abigerges D, Armand J-P, Chabot GG, et al. Phase I and pharmacology study of intoplicine (RP 60475; NSC 645008), a novel topoisomerase I and II inhibitors, in cancer patients. Anti-Cancer Drugs 1996; 7: 166-74.
14. Bissery MC, Andre S, Renard A, et al. Preclinical pharmacology and toxicology of RP 60475, a new benzopyrido-indole. Ann Oncol 1992; 3 (suppl I): 94 (abstr 143).
15. van Gijn R, ten Bokkel Huinink WW, Rodenhuis S, et al. Topoisomerase I/II inhibitor intoplicine administered as a 24 h infusion: phase I and pharmacologic study. Anti-Cancer Drugs 1999; 10: 17-23.