nach oben

Erschienen in:

01.04.2015 | Original Article

Cisplatin in combination with metronomic vinorelbine as front-line treatment in advanced non-small cell lung cancer: a multicenter phase II study of the Hellenic Oncology Research Group (HORG)

verfasst von: P. Katsaounis, A. Kotsakis, S. Agelaki, E. Kontopodis, A. Agelidou, N. Kentepozidis, L. Vamvakas, A. Christopoulou, N. Karachaliou, D. Hatzidaki, V. Georgoulias

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 4/2015

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To evaluate the safety and efficacy of metronomic vinorelbine in combination with cisplatin as first-line treatment in patients with advanced non-small cell lung cancer (NSCLC).

Patients and methods

A total of 41 patients with inoperable stage IIIb or stage IV NSCLC (14 with adenocarcinomas, 19 with squamous cell carcinoma and eight with other types), PS = 0–2, were treated with cisplatin (80 mg/m²) in combination with oral metronomic vinorelbine (60 mg total dose, every other day) in cycles of 21 days.

Results

A total of 35 patients who received at least one cycle of chemotherapy were evaluable for toxicity and response. Partial response was achieved in 13 patients (ORR 37.1 %; CI 21.1–53.1 %) and stable disease in 10 (28.6 %). After a median follow-up period of 26.2 months (range 0.5–33.4 months), the median progression-free survival was 4.2 months and the median overall survival 12.0 months. The 1-year survival rate was 52.6 %. Myelosuppression was the main adverse event with grade 3 and 4 neutropenia occurring in five (14.3 %) and six (17.1 %) patients, respectively. Three of these patients presented with febrile neutropenia and there was one death due to sepsis. Non-hematologic toxicities were mild.

Conclusion

Cisplatin in combination with metronomic vinorelbine is an active, although myelotoxic, therapeutic option in the first-line setting for the treatment of patients with locally advanced and metastatic non-small cell lung cancer, which merits further evaluation in randomized trials.

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90. doi:10.3322/caac.20107 CrossRefPubMed

Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics. CA Cancer J Clin 64(1):9–29. doi:10.3322/caac.21208 CrossRefPubMed

Malvezzi M, Bertuccio P, Levi F, La Vecchia C, Negri E (2014) European cancer mortality predictions for the year 2014. Ann Oncol 25(8):1650–1656. doi:10.1093/annonc/mdu138 CrossRefPubMed

Burdett S, Stephens R, Stewart L, Tierney J, Auperin A, Le Chevalier T, Le Pechoux C, Pignon JP, Arriagada R, Higgins J, Johnson D, van Meerbeeck J et al (2008) Chemotherapy in addition to supportive care improves survival in advanced non-small-cell lung cancer: a systematic review and meta-analysis of individual patient data from 16 randomized controlled trials. J Clin Oncol 26(28):4617–4625. doi:10.1200/JCO.2008.17.7162 CrossRef

Hotta K, Fujiwara Y, Matsuo K, Suzuki T, Kiura K, Tabata M, Takigawa N, Ueoka H, Tanimoto M (2007) Recent improvement in the survival of patients with advanced nonsmall cell lung cancer enrolled in phase III trials of first-line, systemic chemotherapy. Cancer 109(5):939–948. doi:10.1002/cncr.22478 CrossRefPubMed

Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH (2002) Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346(2):92–98. doi:10.1056/NEJMoa011954 CrossRefPubMed

Skipper HE, Schabel FM Jr, Wilcox WS (1964) Experimental evaluation of potential anticancer agents. xiii. on the criteria and kinetics associated with “curability” of experimental leukemia. Cancer Chemother Rep 35:1–111PubMed

Hill DL (1975) A review of cyclophosphamide. Ann Intern Med 83(5):750. doi:10.7326/0003-4819-83-5-750_2

Bocci G, Nicolaou KC, Kerbel RS (2002) Protracted low-dose effects on human endothelial cell proliferation and survival in vitro reveal a selective antiangiogenic window for various chemotherapeutic drugs. Cancer Res 62(23):6938–6943PubMed

10.

Browder T, Butterfield CE, Kraling BM, Shi B, Marshall B, O’Reilly MS, Folkman J (2000) Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res 60(7):1878–1886PubMed

11.

Kerbel RS, Klement G, Pritchard KI, Kamen B (2002) Continuous low-dose anti-angiogenic/metronomic chemotherapy: from the research laboratory into the oncology clinic. Ann Oncol 13(1):12–15CrossRefPubMed

12.

Ghiringhelli F, Menard C, Puig PE, Ladoire S, Roux S, Martin F, Solary E, Le Cesne A, Zitvogel L, Chauffert B (2007) Metronomic cyclophosphamide regimen selectively depletes CD4+ CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother 56(5):641–648. doi:10.1007/s00262-006-0225-8 CrossRefPubMed

13.

Tanaka H, Matsushima H, Mizumoto N, Takashima A (2009) Classification of chemotherapeutic agents based on their differential in vitro effects on dendritic cells. Cancer Res 69(17):6978–6986. doi:10.1158/0008-5472.CAN-09-1101 CrossRefPubMedCentralPubMed

14.

Le Chevalier T, Brisgand D, Douillard JY, Pujol JL, Alberola V, Monnier A, Riviere A, Lianes P, Chomy P, Cigolari S et al (1994) Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: results of a European multicenter trial including 612 patients. J Clin Oncol 12(2):360–367PubMed

15.

Briasoulis E, Pappas P, Puozzo C, Tolis C, Fountzilas G, Dafni U, Marselos M, Pavlidis N (2009) Dose-ranging study of metronomic oral vinorelbine in patients with advanced refractory cancer. Clin Cancer Res 15(20):6454–6461. doi:10.1158/1078-0432.CCR-09-0970 CrossRefPubMed

16.

Pallis AG, Chandrinos V, Pavlakou G, Xenidis N, Varthalitis I, Vardakis N, Vamvakas L, Kontopodis E, Rovithi M, Georgoulias V (2011) A multicenter phase I trial of metronomic oral vinorelbine plus cisplatin in patients with NSCLC. Cancer Chemother Pharmacol 67(6):1239–1245. doi:10.1007/s00280-010-1415-9 CrossRefPubMed

17.

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247. doi:10.1016/j.ejca.2008.10.026 CrossRefPubMed

18.

Delbaldo C, Michiels S, Syz N, Soria JC, Le Chevalier T, Pignon JP (2004) Benefits of adding a drug to a single-agent or a 2-agent chemotherapy regimen in advanced non-small-cell lung cancer: a meta-analysis. JAMA 292(4):470–484. doi:10.1001/jama.292.4.470 CrossRefPubMed

19.

Mir O, Domont J, Cioffi A, Bonvalot S, Boulet B, Le Pechoux C, Terrier P, Spielmann M, Le Cesne A (2011) Feasibility of metronomic oral cyclophosphamide plus prednisolone in elderly patients with inoperable or metastatic soft tissue sarcoma. Eur J Cancer 47(4):515–519. doi:10.1016/j.ejca.2010.11.025 CrossRefPubMed

20.

Baguley BC, Holdaway KM, Thomsen LL, Zhuang L, Zwi LJ (1991) Inhibition of growth of colon 38 adenocarcinoma by vinblastine and colchicine: evidence for a vascular mechanism. Eur J Cancer 27(4):482–487CrossRefPubMed

21.

Denekamp J (1982) Endothelial cell proliferation as a novel approach to targeting tumour therapy. Br J Cancer 45(1):136–139CrossRefPubMedCentralPubMed

22.

Fossella F, Pereira JR, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP (2003) Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol 21(16):3016–3024. doi:10.1200/JCO.2003.12.046 CrossRefPubMed

23.

Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, Leighl N, Mezger J, Archer V, Moore N, Manegold C (2009) Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol 27(8):1227–1234. doi:10.1200/JCO.2007.14.5466 CrossRefPubMed

24.

Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355(24):2542–2550. doi:10.1056/NEJMoa061884 CrossRefPubMed

25.

Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, Leighl N, Mezger J, Archer V, Moore N, Manegold C (2010) Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL). Ann Oncol 21(9):1804–1809. doi:10.1093/annonc/mdq020 CrossRefPubMedCentralPubMed

26.

Morgensztern D, Govindan R (2008) Treatment of patients excluded from Eastern Cooperative Oncology Group 4599 and AVAiL studies: focus on brain metastasis and squamous histology. Clin Lung Cancer 9(Suppl 2):S57–S61. doi:10.3816/CLC.2008.s.009 CrossRefPubMed

27.

Ramalingam SS, Dahlberg SE, Langer CJ, Gray R, Belani CP, Brahmer JR, Sandler AB, Schiller JH, Johnson DH (2008) Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol 26(1):60–65. doi:10.1200/JCO.2007.13.1144 CrossRefPubMed

28.

Zhu J, Sharma DB, Gray SW, Chen AB, Weeks JC, Schrag D (2012) Carboplatin and paclitaxel with vs without bevacizumab in older patients with advanced non-small cell lung cancer. JAMA 307(15):1593–1601. doi:10.1001/jama.2012.454 CrossRefPubMedCentralPubMed

29.

Barletta G, Genova C, Rijavec E, Burrafato G, Biello F, Sini C, Dal Bello MG, Coco S, Truini A, Vanni I, Alama A, Beltramini S, Grassi MA, Boccardo F, Grossi F (2014) Oral vinorelbine in the treatment of non-small-cell lung cancer. Expert Opin Pharmacother 15(11):1585–1599. doi:10.1517/14656566.2014.934224 CrossRefPubMed

Titel: Cisplatin in combination with metronomic vinorelbine as front-line treatment in advanced non-small cell lung cancer: a multicenter phase II study of the Hellenic Oncology Research Group (HORG)
verfasst von: P. Katsaounis
A. Kotsakis
S. Agelaki
E. Kontopodis
A. Agelidou
N. Kentepozidis
L. Vamvakas
A. Christopoulou
N. Karachaliou
D. Hatzidaki
V. Georgoulias
Publikationsdatum: 01.04.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 4/2015
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-015-2707-x

Springer Medizin

Cisplatin in combination with metronomic vinorelbine as front-line treatment in advanced non-small cell lung cancer: a multicenter phase II study of the Hellenic Oncology Research Group (HORG)