nach oben

Clinical and Translational Oncology

Erschienen in:

01.05.2015 | Research Article

The protein kinase C (PKC) inhibitors combined with chemotherapy in the treatment of advanced non-small cell lung cancer: meta-analysis of randomized controlled trials

verfasst von: L. L. Zhang, F. F. Cao, Y. Wang, F. L. Meng, Y. Zhang, D. S. Zhong, Q. H. Zhou

Erschienen in: Clinical and Translational Oncology | Ausgabe 5/2015

Einloggen, um Zugang zu erhalten

Abstract

Background

The application of newer signaling pathway-targeted agents has become an important addition to chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). In this study, we evaluated the efficacy and toxicities of PKC inhibitors combined with chemotherapy versus chemotherapy alone for patients with advanced NSCLC systematically.

Patients and materials

Literature retrieval, trials selection and assessment, data collection, and statistic analysis were performed according to the Cochrane Handbook 5.1.0. The outcome measures were tumor response rate, disease control rate, progression-free survival (PFS), overall survival (OS), and adverse effects.

Results

Five randomized controlled trials, comprising totally 1,005 patients, were included in this study. Meta-analysis showed significantly decreased response rate (RR 0.79; 95 % CI 0.64–0.99) and disease control rate (RR 0.90; 95 % CI 0.82–0.99) in PKC inhibitors-chemotherapy groups versus chemotherapy groups. There was no significant difference between the two treatment groups regarding progression-free survival (PFS, HR 1.05; 95 % CI 0.91–1.22) and overall survival (OS, HR 1.00; 95 % CI 0.86–1.16). The risk of grade 3/4 neutropenia, leucopenia, and thrombosis/embolism increased significantly in PKC inhibitors combination groups as compared with chemotherapy alone groups.

Conclusion

The use of PKC inhibitors in addition to chemotherapy was not a valid alternative for patients with advanced NSCLC.

Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29.CrossRefPubMed

D’Addario G, Fruh M, Reck M, Baumann P, Klepetko W, Felip E, et al. Metastatic non-small-cell lung cancer. ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):vii56–vii64.

Soon YY, Stockler MR, Askie LM, Boyer MJ. Duration of chemotherapy for advanced non-small-cell lung cancer: a systematic review and meta-analysis of randomized trials. J Clin Oncol. 2009;27(20):3277–83.CrossRefPubMed

Clark AS, West KA, Blumberg PM, Dennis PA. Altered protein kinase C (PKC) isoforms in non-small cell lung cancer cells: PKCdelta promotes cellular survival and chemotherapeutic resistance. Cancer Res. 2003;63(4):780–6.PubMed

Martiny-Baron G, Fabbro D. Classical PKC isoforms in cancer. Pharmacol Res. 2007;55(6):477–86.CrossRefPubMed

Winegarden JD, Mauer AM, Gajewski TF, Hoffman PC, Krauss S, Rudin CM, et al. A phase II study of bryostatin-1 and paclitaxel in patients with advanced non-small cell lung cancer. Lung Cancer. 2003;39(2):191–6.CrossRefPubMed

Edelman MJ, Bauer KS Jr, Wu S, Smith R, Bisacia S, Dancey J. Phase I and pharmacokinetic study of 7-hydroxystaurosporine and carboplatin in advanced solid tumors. Clin Cancer Res. 2007;13(9):2667–74.CrossRefPubMed

Mack PC, Gandara DR, Lau AH, Lara PN Jr, Edelman MJ, Gumerlock PH. Cell cycle-dependent potentiation of cisplatin by UCN-01 in non-small-cell lung carcinoma. Cancer Chemother Pharmacol. 2003;51(4):337–48.PubMed

Monnerat C, Henriksson R, Le Chevalier T, Novello S, Berthaud P, Faivre S, et al. 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. Ann Oncol. 2004;15(2):316–23.CrossRefPubMed

10.

Vansteenkiste J, Canon JL, Riska H, Pirker R, Peterson P, John W, et al. Randomized phase II evaluation of aprinocarsen in combination with gemcitabine and cisplatin for patients with advanced/metastatic non-small cell lung cancer. Invest New Drugs. 2005;23(3):263–9.CrossRefPubMed

11.

Socinski MA, Raju RN, Stinchcombe T, Kocs DM, Couch LS, Barrera D, et al. Randomized, phase II trial of pemetrexed and carboplatin with or without enzastaurin versus docetaxel and carboplatin as first-line treatment of patients with stage IIIB/IV non-small-cell lung cancer. J Thorac Oncol. 2010;5(12):1963–9.CrossRefPubMed

12.

Mansfield AS, Fields AP, Jatoi A, Qi Y, Adjei AA, Erlichman C, et al. Phase I dose escalation study of the PKCι inhibitor aurothiomalate for advanced non-small-cell lung cancer, ovarian cancer, and pancreatic cancer. Anticancer Drugs. 2013;24(10):1079–83.CrossRefPubMedCentralPubMed

13.

Nakajima E, Helfrich B, Chan D, Zhang Z, Hirsch FR, Chen V, et al. Enzastaurin, a protein kinase C-beta-selective inhibitor, inhibits the growth of SCLC and NSCLC cell lines. J Clin Oncol. 2006;24:612s (abstract 13138).

14.

Giovannetti E, Honeywell R, Hanauske AR, Tekle C, Kuenen B, Sigmond J, et al. Pharmacological aspects of the enzastaurin-pemetrexed combination in non-small cell lung cancer (NSCLC). Curr Drug Targets. 2010;11(1):12–28.CrossRefPubMed

15.

Carducci MA, Musib L, Kies MS, Pili R, Truong M, Brahmer JR, et al. Phase I dose escalation and pharmacokinetic study of enzastaurin, an oral protein kinase C beta inhibitor, in patients with advanced cancer. J Clin Oncol. 2006;24:4092–9.CrossRefPubMed

16.

Villalona-Calero MA, Ritch P, Figueroa JA, Otterson GA, Belt R, Dow E, et al. A phase I/II study of LY900003, an antisense inhibitor of protein kinase C-alpha, in combination with cisplatin and gemcitabine in patients with advanced non-small cell lung cancer. Clin Cancer Res. 2004;10:6086–93.CrossRefPubMed

17.

Casey EM, Harb W, Bradford D, Bufill J, Nattam S, Patel J, et al. Randomized, double-blinded, multicenter, phase II study of pemetrexed, carboplat in, and bevacizumab with enzastaurin or placebo in chemonaïve patients with stage IIIB/IV non-small cell lung cancer: Hoosier Oncology Group LUN06-116. J Thorac Oncol. 2010;5(11):1815–20.CrossRefPubMed

18.

Chiappori A, Bepler G, Barlesi F, Soria JC, Reck M, Bearz A, et al. Phase II, double-blinded, randomized study of enzastaurin plus pemetrexed as second-line therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol. 2010;5(3):369–75.CrossRefPubMed

19.

Paz-Ares L, Douillard JY, Koralewski P, Manegold C, Smit EF, Reyes JM, et al. Phase III study of gemcitabine and cisplatin with or without aprinocarsen, a protein kinase C-alpha antisense oligonucleotide, in patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2006;24(9):1428–34.CrossRefPubMed

20.

Lee SH, Chen T, Zhou J, Hofmann J, Bepler G. Protein kinase C-beta gene variants, pathway activation, and enzastaurin activity in lung cancer. Clin Lung Cancer. 2010;11:169–75.CrossRefPubMedCentralPubMed

21.

Ritch P, Rudin CM, Bitran JD, Edelman MJ, Makalinao A, Irwin D, et al. Phase II study of PKC-alpha antisense oligonucleotide aprinocarsen in combination with gemcitabine and carboplatin in patients with advanced non-small cell lung cancer. Lung Cancer. 2006;52(2):173–80.CrossRefPubMed

22.

Körner A, Mudduluru G, Manegold C, Allgayer H. Enzastaurin inhibits invasion and metastasis in lung cancer by diverse molecules. Br J Cancer. 2010;103(6):802–11.CrossRefPubMedCentralPubMed

23.

Kuo WL, Liu J, Mauceri H, Vokes EE, Weichselbaum R, Rosner MR, et al. Efficacy of the multi-kinase inhibitor enzastaurin is dependent on cellular signaling context. Mol Cancer Ther. 2010;9(10):2814–24.CrossRefPubMedCentralPubMed

24.

Regala RP, Thompson EA, Fields AP. Atypical protein kinase C iota expression and aurothiomalate sensitivity in human lung cancer cells. Cancer Res. 2008;68(14):5888–95.CrossRefPubMedCentralPubMed

25.

Justilien V, Walsh MP, Ali SA, Thompson EA, Murray NR, Fields AP. The PRKCI and SOX2 oncogenes are coamplified and cooperate to activate Hedgehog signaling in lung squamous cell carcinoma. Cancer Cell. 2014;25(2):139–51.CrossRefPubMedCentralPubMed

26.

Kim ES, Neubauer M, Cohn A, Schwartzberg L, Garbo L, Caton J, et al. Docetaxed or pemetrexed with of without cetuximab in recurrent or progressive non-small cell lung cancer after platinum-based therapy: a phase 3, open-label, randomised trial. Lancet Oncol. 2013;14(13):1326–36.CrossRefPubMed

27.

Dy GK, Mandrekar SJ, Nelson GD, Meyers JP, Adjei AA, Ross HJ, et al. A randomized phase II study of gemcitabine and carboplatin with or without cediranib as first-line therapy in advanced non–small-cell lung cancer, north central cancer treatment group study N0528. J Thorac Oncol. 2013;8(1):79–88.CrossRefPubMedCentralPubMed

28.

Harper MT, Poole AW. Diverse functions of protein kinase C isoforms in platelet activation and thrombus formation. J Thromb Haemost. 2010;8(3):454–62.CrossRefPubMed

29.

Fisher MD, D’Orazio A. Phase II and III trials: comparison of four chemotherapy regimens in advanced non small-cell lung cancer (ECOG 1594). Clin Lung Cancer. 2000;2(1):21–2.CrossRefPubMed

30.

Gridelli C, de Marinis F, Pujol JL, Reck M, Ramlau R, Parente B, et al. Safety, resource use, and quality of life in paramount: a phase III study of maintenance pemetrexed versus placebo after induction pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Thorac Oncol. 2012;7(11):1713–21.CrossRefPubMed

Titel: The protein kinase C (PKC) inhibitors combined with chemotherapy in the treatment of advanced non-small cell lung cancer: meta-analysis of randomized controlled trials
verfasst von: L. L. Zhang
F. F. Cao
Y. Wang
F. L. Meng
Y. Zhang
D. S. Zhong
Q. H. Zhou
Publikationsdatum: 01.05.2015
Verlag: Springer Milan
Erschienen in: Clinical and Translational Oncology / Ausgabe 5/2015
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI: https://doi.org/10.1007/s12094-014-1241-3

Neu im Fachgebiet Onkologie

23.04.2024 | Medikamente in Schwangerschaft und Stillzeit | Nachrichten

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

The protein kinase C (PKC) inhibitors combined with chemotherapy in the treatment of advanced non-small cell lung cancer: meta-analysis of randomized controlled trials

Abstract

Background

Patients and materials

Results

Conclusion

Neu im Fachgebiet Onkologie

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Stufenschema weist Prostatakarzinom zuverlässig nach

Update Onkologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Background

Patients and materials

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2015

Comparing CTVs for permanent prostate brachytherapy

Gemcitabine plus capecitabine (Gem–Cape) biweekly in chemorefractory metastatic colorectal cancer

Tissue fatty acid composition and secretory phospholipase-A2 activity in oral squamous cell carcinoma

Immunotherapy in prostate cancer: review of the current evidence

High serum microRNA-335 level predicts aggressive tumor progression and unfavorable prognosis in pediatric acute myeloid leukemia

Gestational trophoblastic neoplasia: treatment outcomes from a single institutional experience

Neu im Fachgebiet Onkologie

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Stufenschema weist Prostatakarzinom zuverlässig nach

Update Onkologie