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Phase I Trials of Ormaplatin (NSC 363812)

  • Michaele C. Christian

Abstract

Tetrachloro(d,l-trans)1,2-diaminocyclohexaneplatinum (IV), ormaplatin (OP), NSC 363812, formerly called tetraplatin, is a second generation platinum (IV) compound which has been evaluated in clinical trials sponsored by the National Cancer Institute (NCI) in collaboration with Upjohn. Interest in this group of compounds was stimulated by structure-activity studies by Burchenal et al.,(1) which suggested that platinum compounds containing the 1,2-diaminocyclohexane (DACH) carrier ligand retained activity in vitro and in vivo against L1210 and P388 murine leukemia cell lines with acquired resistance to cisplatin. In addition, in preclinical antitumor testing, OP demonstrated broad spectrum activity comparable to or superior to cisplatin (CDDP) against a variety of murine and human tumor models (2,3) however, its activity in other models was variable and against a screening panel of 16 human ovarian cancer cell lines was disappointing (4).

Keywords

Sural Nerve Human Ovarian Cancer Cell Line Total Platinum Ultrafilterable Platinum Prophylactic Antiemetic 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Burchenal JH, Kalaher K, Dew K, et al. Studies of cross-resistance, synergistic combinations and blocking of activity of platinum derivatives. Biochimie 60(9):961–965, 1978.CrossRefGoogle Scholar
  2. 2.
    Anderson WK, Quagliato DA, Haugwitz RD, et al. Synthesis, physical properties, and antitumor activity of tetraplatin and related tetrachloroplatinum(IV) stereoisomers of 1,2-diaminocyclohexane. Cancer Treat Rep 70(8):997–1002, 1986.PubMedGoogle Scholar
  3. 3.
    Behrens BC, Hamilton TC, Masuda H, et al. Characterization of a cis-diamminedichloroplatinum(II)-resistant human ovarian cancer cell line and its use in evaluation of platinum analogues. Cancer Res 47(2):414–418, 1987.PubMedGoogle Scholar
  4. 4.
    Harrap KR, Jones M, Siracky J, et al. The establishment, characterization and calibration of human ovarian carcinoma xenografts for the evaluation of novel platinum anticancer drugs. Ann Oncol 1(1):65–76, 1990.PubMedGoogle Scholar
  5. 5.
    Smith JH, Smith MA, Litterst CL, et al. Comparative toxicity and renal distribution of the platinum analogs tetraplatin, CHIP, and cisplatin at equimolar doses in the Fischer 344 rat. Fundam Appl Toxicol 10:45–61, 1988.CrossRefPubMedGoogle Scholar
  6. 6.
    Smith JH, Smith MA, Litterst CL, et al. In vivo biochemical indices of nephrotoxicity of platinum analogs tetraplatin, CHIP, and cisplatin at equimolar doses in the Fischer 344 rat. Fundam Appl Toxicol 10:62–72, 1988.CrossRefPubMedGoogle Scholar
  7. 7.
    Gandara DR, Wold H, Perez E, et al. High-dose cisplatin in hypertonic saline; reduced toxicity of a modified dose-schedule and correlation with plasma pharmacokinetics. A Northern California Oncology Group pilot study in non-small cell lung cancer. J Clin Oncol 4:1787–1793, 1989.Google Scholar
  8. 8.
    Christian MC, Kohn E, Sarosy G, et al. Phase I and pharmacologie study of ormaplatin (op)/tetraplatin. Proc Am Soc Clin Oncol 11:117, 1992.Google Scholar
  9. 9.
    Tutsch MD, Arzoomanian RZ, Alberti D, et al. Phase I trial and pharmacokinetic study of ormaplatin. Proc AACR 33:536,1992.Google Scholar
  10. 10.
    O’Rourke TJ, Weiss, New P, et al. Phase I trial of ormaplatin (tetraplatin, NSC 363812). Anti-Cancer Drugs 5:520–525, 1994.CrossRefPubMedGoogle Scholar
  11. 11.
    Petros WP, Chaney SG, Smith DC, et al. Pharmacokinetic and biotransformation studies of ormaplatin in conjunction with a phase I clinical trial. Cancer Chemother Pharmacol 33:347–354, 1994.CrossRefPubMedGoogle Scholar
  12. 12.
    Schilder RJ, LaCreta FP, Perez RP, et al. Phase I and pharmacokinetic study of ormaplatin (tetraplatin, NSC 363812) administered on a day 1 and day 8 schedule, Cancer Res 54(3):709–717, 1994.PubMedGoogle Scholar
  13. 13.
    Plaxe SC, Braly PS, Freddo JL, et al. Phase I and pharmacokinetic study of intraperitoneal ormaplatin. Gynecologic Oncology 51:72–77, 1993.CrossRefPubMedGoogle Scholar
  14. 14.
    Chaney SG, Wyrick S, Till GK. In vitro biotransformations of tetrachloro(d,l-trans)1,2-diaminocyclohexaneplatinum (IV) (tetraplatin) in rat plasma. Cancer Res 50:4539, 1990.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Michaele C. Christian
    • 1
  1. 1.Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer TreatmentNational Cancer InstituteBethesdaUSA

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