Phase I evaluation of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase C-alpha, in patients with advanced cancer

Journal of Clinical Oncology

Volumn 17, Issue 11, 1999, Pages 3586-3595

  Nemunaitis, John ^a   Holmlund, J T ^a   Kraynak, M ^a   Richards, D ^a   Bruce, J ^a   Ognoskie, N ^a   Kwoh, T J ^a   Geary, R ^a   Dorr, A ^a   Von Hoff, D ^a   Eckhardt, S G ^a  

^a BAYLOR UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ISIS 3521; PROTEIN KINASE C;

ADULT; ADVANCED CANCER; AGED; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CHILL; CLINICAL ARTICLE; CLINICAL TRIAL; DOSE RESPONSE; DRUG CLEARANCE; DRUG HALF LIFE; FATIGUE; FEMALE; FEVER; HUMAN; MALE; MAXIMUM PERMISSIBLE DOSE; NAUSEA; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; THROMBOCYTOPENIA; VOMITING;

EID: 0032730429     PISSN: 0732183X     EISSN: None     Source Type: Journal    
DOI: 10.1200/JCO.1999.17.11.3586     Document Type: Article

References (41)

1. Nishizuka Y: The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature 334:661-665, 1988
2. Basu A: The potential of protein kinase C as a target for anticancer treatment. Pharmacol Ther 59:257-280, 1993
3. Blobe GC, Obeid LM, Hannun YA: Regulation of protein kinase C and role in cancer biology. Cancer Metastasis Rev 13:411-431, 1994
4. Yuspa SH: The pathogenesis of squamous cell carcinoma: Lessons learned from studies of skin carcinogenesis. Cancer Res 54:1178-1189, 1994
5. Ha genes are mediated by protein kinase C-alpha. Cancer Res 54:6413-6420, 1994
6. Ways D, Kikoly K, de Vente CA, et al: MCF-7 breast cancer cells transfected with protein kinase C-alpha exhibit altered expression of other protein kinase C isoforms and display a more aggressive phenotype. J Clin Invest 95:1906-1915, 1995
7. O'Brien CA, Vogel VG, Singletary SE, et al: Elevated protein kinase C expression in human breast tumor biopsies relative to normal breast tissue. Cancer Res 49:3215-3217, 1989
8. Henttu P, Vihko P: The protein kinase C activator, phorbol ester, elicits disparate functional responses in androgen-sensitive and androgen-independent human prostatic cancer cells. Biochem Biophys Res Commun 244:167-171, 1998
9. Perletti GP, Smeraldi C, Porro D, et al: Involvement of the alpha isoenzyme of protein kinase C in the growth inhibition induced by phorbol esters in MH1C1 hepatoma cells. Biochem Biophys Res Commun 205:1589-1594, 1994
10. Adesina AM, Dolley N, Young VW, et al: Differential role for protein kinase C-mediated signaling in the proliferation of medulloblastoma cell lines. Int J Oncol 12:759-768, 1998
11. Miligan JF, Matteucci MD, Martin JC: Current concepts in antisense drug design. J Med Chem 36:1923-1927, 1993
12. Crooke ST: Therapeutic applications of oligonucleotides. Annu Rev Pharmacol Toxicol 32:329-335, 1992
13. Crooke ST: Progress in antisense therapeutics. Hematol Pathol 9:59-72, 1995
14. Crooke ST, Bennett CF: Progress in antisense oligonucleotides therapeutics. Annu Rev Pharmacol Toxicol 36:107-129, 1996
15. Orr RM, Monia BP: Antisense therapy for cancer. Mol Ther 1:102-108, 1998
16. Dean NM, McKay R, Condon TP, et al: Inhibition of protein kinase C-I expression in human A549 cells by antisense oligonucleotides inhibits induction of intercellular adhesion molecule 1 (ICAM-1) mRNA by phorbol esters. J Biol Chem 269:16416-16424, 1994
17. Investigator's brochure: ISIS 3521 (CGP 64128A). Carlsbad, CA, Isis Pharmaceuticals, March 1998
18. Dean N, McKay R, Miraglia L, et al: Inhibition of growth of human tumor cell lines in nude mice by an antisense oligonucleotide inhibitor of protein kinase C-alpha expression. Cancer Res 56:3499-3507, 1996
19. Lee YS, Dlugosz AA, McKay R, et al: Definition by specific antisense oligonucleotides of a role for protein kinase C-alpha in expression of differentiation markers in normal and neoplastic mouse epidermal keratinocytes. Mol Carcinog 18:44-53, 1997
20. Yazaki T, Ahmad S, Chahlavi A, et al: Treatment of glioblastoma U-87 by systemic administration of an antisense protein kinase C-alpha phosphorothioate oligodeoxynucleotide. Mol Pharmacol 50:236-242, 1996
21. Dean NM, McKay R: Inhibition of protein kinase C-alpha expression in mice after systemic administration of phosphorothioate antisense oligodeoxynucleotides. Proc Natl Acad Sci U S A 91:11762-11766, 1994
22. Geary RS, Leeds JM, Henry SP, et al: Antisense oligonucleotide inhibitors for the treatment of cancer: I. Pharmacokinetic properties of phosphorothioate oligodeoxynucleotides. Anticancer Drug Des 12:383-393, 1997
23. Henry SP, Taylor J, Midgley L, et al: Evaluation of the toxicity of ISIS 2302, a phosphorothioate oligonucleotide, in a 4-week study in CD-1 mice. Antisense Nucleic Acid Drug Dev 7:473-481, 1997
24. Henry SP, Monteith D, Bennett F, et al: Toxicological and pharmacokinetic properties of chemically modified antisense oligonucleotide inhibitors of PKC-alpha and C-raf kinase. Anticancer Drug Des 12:409-420, 1997
25. Henry SP, Grillone LR, Orr JL, et al: Comparison of the toxicity profiles of ISIS 1082 and ISIS 2105, phosphorothioate oligonucleotides, following subacute intradermal administration in Sprague-Dawley rats. Toxicology 116:77-88, 1997
26. Henry SP, Monteith D, Levin AA: Antisense oligonucleotide inhibitors for the treatment of cancer: II. Toxicological properties of phosphorothioate oligodeoxynucleotides. Anticancer Drug Des 12:395-408, 1997
27. Henry SP, Giclas PC, Leeds JM, et al: Activation of the alternative pathway of complement by a phosphorothioate oligonucleotide: Potential mechanism of action. J Pharmacol Exp Ther 281:810-816, 1997
28. Galbraith WM, Hobson WC, Giclas PC, et al: Complement activation and hemodynamic changes following intravenous administration of phosphorothioate oligonucleotides in the monkey. Antisense Res Dev 4:201-206, 1994
29. Glover JM, Leeds JM, Mant TJK, et al: Phase I safety and pharmacokinetic profile of an intercellular adhesion molecule-1 antisense oligodeoxynucleotide (ISIS 2302). J Pharmacol Exp Ther 282: 1173-1180, 1997
30. Yacyshyn BR, Bowen-Yacyshyn MB, Jewell L, et al: A placebo-controlled trial of ICAM-1 antisense oligonucleotide in the treatment of Crohn's disease. Gastroenterology 114:1133-1142, 1998
31. Wyrzykiewicz TK, Cole DL: Stereo-reproducibility of the phosphoramidite method in the synthesis of oligonucleotide phosphorothioates. Biorg Chem 23:33-41, 1995
32. Leeds JM, Graham MJ, Truong L, et al: Quantitation of phosphorothioate oligonucleotides in human plasma. Anal Biochem 235:36-43, 1996
33. Bishop MR, Iversen P, Bayever E, et al: Phase I trial of antisense oligonucleotide OL (1) p53 in hematologic malignancies. J Clin Oncol 14:1320-1326, 1996
34. Cossum PA, Troung L, Owens SR, et al: Pharmacokinetics of a C-labeled phosphorothioate oligonucleotide. ISIS 2105, after intradermal administration to rats. J Pharmacol Exp Ther 269:89-94, 1994
35. Sands H, Gorey-Feret LJ, Cocuzza AJ, et al: Biodistribution and metabolism of internally H-labeled oligonucleotides: I. Comparison of phosphorodiester and phosphorothioate. Mol Pharmacol 45:932-943, 1994
36. Zhang R, Diasio RB, Lu Z, et al: Pharmacokinetics and tissue distribution in rats of an oligodeoxynucleotide phosphorothioate (GEM 91) developed as a therapeutic agent virus type-1. Biochem Pharmacol 49:929-939, 1995
37. Levin AA, Monteith DK, Leeds JM, et al: Toxicity of oligodeoxynucleotide therapeutic agents, in Crooke ST (ed): Handbook of Experimental Pharmacology: Antisense Research and Application (vol 131). Berlin, Germany, Springer-Verlag, 1998, pp 169-215
38. Sikic BI, Yuen AR, Advani R, et al: Antisense oligonucleotide therapy targeted to protein kinase C-alpha (ISIS 3521/CGP 64128A) by 21 day infusion: Results of the Phase I trial and activity in ovarian carcinomas. Proc Am Soc Clin Oncol 17:429a, 1998 (abstr 1654)
39. Webb A, Cunningham D, Cotter F, et al: BCL-2 antisense therapy in patients with non-Hodgkin lymphoma. Lancet 349:1137-1141, 1997
40. Krieg AM, Yi A-K, Matson S, et al: CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 374:546-549, 1995
41. Boggs RT, McGraw K, Condon T, et al: Characterization and modulation of immune stimulation by modified oligonucleotides. Antisense Nucleic Acid Drug Dev 7:461-471, 1997