Phase I study of PKC412 (N-benzoyl-staurosporine), a novel oral protein kinase C inhibitor, combined with gemcitabine and cisplatin in patients with non-small-cell lung cancer

Annals of Oncology

Volumn 15, Issue 2, 2004, Pages 316-323

  Monnerat, C ^a   Henriksson, R ^b   Le Chevalier, T ^a   Novello, S ^a   Berthaud, P ^a   Faivre, S ^a   Raymond, E ^a  

^a INSTITUT GUSTAVE ROUSSY   (France)

^b Department of Oncology ^*  (Sweden)

Author keywords

Anti angiogenesis; Cell cycle inhibitor; Protein kinase C

Indexed keywords

7 HYDROXYSTAUROSPORINE; ANTIEMETIC AGENT; BROMAZEPAM; CGP 52421; CGP 62221; CISPLATIN; DEXAMETHASONE; GEMCITABINE; IMMUNOMODULATING AGENT; METHYLPREDNISOLONE; METOCLOPRAMIDE; MIDOSTAURIN; MITOMYCIN C; NITROSOUREA DERIVATIVE; ONDANSETRON; PREDNISONE; PROTEIN KINASE C INHIBITOR; STAUROSPORINE DERIVATIVE; UNCLASSIFIED DRUG;

ADULT; ADVANCED CANCER; AGED; ALOPECIA; ANEMIA; ARTICLE; ASTHENIA; CANCER COMBINATION CHEMOTHERAPY; CLINICAL ARTICLE; CLINICAL OBSERVATION; CLINICAL TRIAL; COHORT ANALYSIS; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DOSE RESPONSE; DRUG HALF LIFE; DRUG METABOLISM; DRUG SAFETY; DRUG STRUCTURE; EXPERIMENTAL DESIGN; FATIGUE; FEMALE; HEADACHE; HUMAN; LIVER TOXICITY; LOW DRUG DOSE; LUNG NON SMALL CELL CANCER; MALE; MAXIMUM TOLERATED DOSE; MEDICAL ASSESSMENT; NAUSEA AND VOMITING; NEPHROTOXICITY; NEUROTOXICITY; NEUTROPENIA; OTOTOXICITY; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION; THROMBOCYTOPENIA; TREATMENT WITHDRAWAL;

ADMINISTRATION, ORAL; ADULT; AGED; ANGIOGENESIS INHIBITORS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; ASTHENIA; CARCINOMA, NON-SMALL-CELL LUNG; CISPLATIN; DEOXYCYTIDINE; DIARRHEA; ENZYME INHIBITORS; FEMALE; HUMANS; INFUSIONS, INTRAVENOUS; LUNG NEOPLASMS; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; PROTEIN KINASE C; STAUROSPORINE;

EID: 1342310067     PISSN: 09237534     EISSN: None     Source Type: Journal    
DOI: 10.1093/annonc/mdh052     Document Type: Article

References (30)

1. Goekjian PG, Jirousek MR. Protein kinase C inhibitors as novel anticancer drugs. Expert Opin Investig Drugs 2001; 10: 2117-2140.
2. Dekker LV, Parker PJ. Protein kinase C-a question of specificity. Trends Biochem Sci 1994; 19: 73-77.
3. Hofmann J. Modulation of protein kinase C in antitumor treatment. Rev Physiol Biochem Pharmacol 2001; 142: 1-96.
4. Jones SM, Kazlauskas A. Connecting signaling and cell cycle progression in growth factor-stimulated cells. Oncogene 2000; 19: 5558-5567.
5. Buchner K. The role of protein kinase C in the regulation of cell growth and in signalling to the cell nucleus. J Cancer Res Clin Oncol 2000; 126: 1-11.
6. Antoniades HN, Galanopoulos T, Neville-Golden J, O'Hara CJ. Malignant epithelial cells in primary human lung carcinomas coexpress in vivo platelet-derived growth factor (PDGF) and PDGF receptor mRNAs and their protein products. Proc Natl Acad Sci USA 1992; 89: 3942-3946.
7. Vignaud JM, Marie B, Klein N et al. The role of platelet-derived growth factor production by tumor-associated macrophages in tumor stroma formation in lung cancer. Cancer Res 1994; 54: 5455-5463.
8. Ohta Y, Endo Y, Tanaka M et al. Significance of vascular endothelial growth factor messenger RNA expression in primary lung cancer. Clin Cancer Res 1996; 2: 1411-1416.
9. Skobe M, Rockwell P, Goldstein N et al. Halting angiogenesis suppresses carcinoma cell invasion. Nat Med 1997; 3: 1222-1227.
10. Sausville EA, Arbuck SG, Messmann R et al. Phase I trial of 72-hour continuous infusion UCN-01 in patients with refractory neoplasms. J Clin Oncol 2001; 19: 2319-2333.
11. Propper DJ, McDonald AC, Man A et al. Phase I and pharmacokinetic study of PKC412, an inhibitor of protein kinase C. J Clin Oncol 2001; 19: 1485-1492.
12. Nemunaitis J, Holmlund JT, Kraynak M et al. Phase I evaluation of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase C-α, in patients with advanced cancer. J Clin Oncol 1999; 17: 3586-3595.
13. Andrejauskas-Buchdunger E, Regenass U. Differential inhibition of the epidermal growth factor-, platelet-derived growth factor-, and protein kinase C-mediated signal transduction pathways by the staurosporine derivative CGP 41251. Cancer Res 1992; 52: 5353-5358.
14. Begemann M, Kashimawo SA, Heitjan DF et al. Treatment of human glioblastoma cells with the staurosporine derivative CGP 41251 inhibits CDC2 and CDK2 kinase activity and increases radiation sensitivity. Anticancer Res 1998; 18: 2275-2282.
15. Fabbro D, Ruetz S, Bodis S et al. PKC412-a protein kinase inhibitor with a broad therapeutic potential. Anticancer Drug Des 2000; 15: 17-28.
16. Fabbro D, Buchdunger E, Wood J et al. Inhibitors of protein kinases: CGP 41251, a protein kinase inhibitor with potential as an anticancer agent. Pharmacol Ther 1999; 82: 293-301.
17. National Cancer Institute: common toxicity criteria, version 2. [online] http://ctep.cancer.gov/reporting/ctc.html (2 December 2003, date last accessed). Bethesda, MD: National Cancer Institute 1999.
18. Green S, Weiss GR. Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria. Invest New Drugs 1992; 10: 239-253.
19. Gralla RJ, Osoba D, Kris MG et al. Recommendations for the use of antiemetics: evidence-based, clinical practice guidelines. American Society of Clinical Oncology. J Clin Oncol 1999; 17: 2971-2994.
20. O'Quigley J, Pepe M, Fisher L. Continual reassessment method: a practical design for phase 1 clinical trials in cancer. Biometrics 1990; 46: 33-48.
21. van Gijn R, van Tellingen O, de Clippeleir JJ et al. Analytical procedure for the determination of the new antitumour drug N-benzoylstaurosporine and three potential metabolites in human plasma by reversed-phase high-performance liquid chromatography. J Chromatogr B Biomed Appl 1995; 667: 269-276.
22. Yuen AR, Halsey J, Fisher GA et al. Phase I study of an antisense oligonucleotide to protein kinase C-α (ISIS 3521/CGP 64128A) in patients with cancer. Clin Cancer Res 1999; 5: 3357-3363.
23. Fischer T, Beck J, Petersen V et al. A phase I and pharmacokinetic trial of PKC412, an inhibitor of protein kinase C, in combination with taxol and carboplatin in patients with advanced NSCLC. Proc Am Soc Clin Oncol 2001; 20: a1322.
24. Garcia-Carbonero R, Eder JP, Clark IF et al. Phase I and pharmacokinetic study of 4′-N-benzoyl-staurosporine (PKC412) combined with 5-fluorouracil in patients with advanced solid malignancies. Proc Am Soc Clin Oncol 2001; 20: a329.
25. Crinò L, Scagliotti GV, Ricci S et al. Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: a randomized phase III study of the Italian Lung Cancer Project. J Clin Oncol 1999; 17: 3522-3530.
26. Meyer T, Regenass U, Fabbro D et al. A derivative of staurosporine (CGP 41 251) shows selectivity for protein kinase C inhibition and in vitro anti-proliferative as well as in vivo anti-tumor activity. Int J Cancer 1989; 43: 851-856.
27. Fuse E, Tanii H, Kurata N et al. Unpredicted clinical pharmacology of UCN-01 caused by specific binding to human α1-acid glycoprotein. Cancer Res 1998; 58: 3248-3253.
28. Berry BW, Erlichman C. Clinical Pharmacology of Anticancer Drugs. In Schilsky RL, Milano GA, Ratain MJ (eds): Principles of Antineoplastic Drug Development and Pharmacology. New York, NY: Marcel Dekker 1996; 75-122.
29. Thavasu P, Propper D, McDonald A et al. The protein kinase C inhibitor CGP41251 suppresses cytokine release and extracellular signal-regulated kinase 2 expression in cancer patients. Cancer Res 1999; 59: 3980-3984.
30. Senderowicz AM, Sausville EA. Preclinical and clinical development of cyclin-dependent kinase modulators. J Natl Cancer Inst 2000; 92: 376-387.