Aan dit artikel is enkele uren gewerkt. Opzoeken, vertalen, plaatsen enz. Als u ons wilt ondersteunen dan kan dat via een al of niet anonieme donatie. Elk bedrag is welkom hoe klein ook. Klik hier als u ons wilt helpen kanker-actueel online te houden Wij zijn een ANBI organisatie en dus is uw donatie aftrekbaar voor de belasting

6 juni 2012: toegevoegd een link naar het gratis in te zien volledige studie rapport van onderstaand abstract: Gefitinib or Chemotherapy for Non–Small-Cell Lung Cancer with Mutated EGFR. Referentielijst staat onderaan abstract

26 jun 2010: Bron ASCO en N Engl J Med. 2010 Jun 24;362(25):2380-8.

Iressa verdubbelt ziektevrije tijd en geeft hoog significant meer completere remissies dan een standaard aanpak met chemo bij longkankerpatienten met de juiste EGRF receptoren. Dit blijkt uit een langjarige gerandomiseerde fase III studie bij 230 longkankerpatienten geselecteerd vooraf op EGRF mutatie. De verschillen waren significant in het voordeel van de Iressagroep: in ziektevrije tijd, 5,4 versus 10,8 maanden, complete remissies 30,7% versus 73,7% en de overall mediane overleving ging van 23,6 in de chemogroep naar 30,5 maanden in de Iressagroep. Voor longkankerpatienten met de juiste receptoren zal nu Iressa iof Tarceva worden voorgesteld als behandeling voor gevorderde longkanker. De studie werd gepubliceerd in the New England Journal of Medicine. Hier het abstract en lees op Medscape een uitgebreidere toelichting op deze studie.

N Engl J Med. 2010 Jun 24;362(25):2380-8.

Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR.

Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group.

Collaborators (48)

Miyagi Cancer Center, Miyagi, Japan.

Abstract

BACKGROUND: Non-small-cell lung cancer with sensitive mutations of the epidermal growth factor receptor (EGFR) is highly responsive to EGFR tyrosine kinase inhibitors such as gefitinib, but little is known about how its efficacy and safety profile compares with that of standard chemotherapy.

METHODS: We randomly assigned 230 patients with metastatic, non-small-cell lung cancer and EGFR mutations who had not previously received chemotherapy to receive gefitinib or carboplatin-paclitaxel. The primary end point was progression-free survival; secondary end points included overall survival, response rate, and toxic effects. RESULTS: In the planned interim analysis of data for the first 200 patients, progression-free survival was significantly longer in the gefitinib group than in the standard-chemotherapy group (hazard ratio for death or disease progression with gefitinib, 0.36; P<0.001), resulting in early termination of the study. The gefitinib group had a significantly longer median progression-free survival (10.8 months, vs. 5.4 months in the chemotherapy group; hazard ratio, 0.30; 95% confidence interval, 0.22 to 0.41; P<0.001), as well as a higher response rate (73.7% vs. 30.7%, P<0.001). The median overall survival was 30.5 months in the gefitinib group and 23.6 months in the chemotherapy group (P=0.31). The most common adverse events in the gefitinib group were rash (71.1%) and elevated aminotransferase levels (55.3%), and in the chemotherapy group, neutropenia (77.0%), anemia (64.6%), appetite loss (56.6%), and sensory neuropathy (54.9%). One patient receiving gefitinib died from interstitial lung disease.

CONCLUSIONS: First-line gefitinib for patients with advanced non-small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival, with acceptable toxicity, as compared with standard chemotherapy. (UMIN-CTR number, C000000376.) 2010 Massachusetts Medical Society

PMID: 20573926 [PubMed - in process]

References

1

Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002;346:92-98
Full Text | Web of Science | Medline

2

Ohe Y, Ohashi Y, Kubota K, et al. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan. Ann Oncol 2007;18:317-323
CrossRef | Web of Science | Medline

3

Fukuoka M, Yano S, Giaccone G, et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (the IDEAL 1 Trial). J Clin Oncol 2003;21:2237-2246[Erratum, J Clin Oncol 2004;22:4811.]
CrossRef | Web of Science | Medline

4

Kris MG, Natale RB, Herbst RS, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA 2003;290:2149-2158
CrossRef | Web of Science | Medline

5

Kim ES, Hirsh V, Mok T, et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet 2008;372:1809-1818
CrossRef | Web of Science | Medline

6

Maruyama R, Nishiwaki Y, Tamura T, et al. Phase III study, V-15-32, of gefitinib versus docetaxel in previously treated Japanese patients with non-small-cell lung cancer. J Clin Oncol 2008;26:4244-4252
CrossRef | Web of Science | Medline

7

Mok TS, Wu Y-L, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009;361:947-957
Full Text | Web of Science | Medline

8

Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129-2139
Full Text | Web of Science | Medline

9

Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004;304:1497-1500
CrossRef | Web of Science | Medline

10

Mitsudomi T, Kosaka T, Endoh H, et al. Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence. J Clin Oncol 2005;23:2513-2520
CrossRef | Web of Science | Medline

11

Toyooka S, Takano T, Kosaka T, et al. Epidermal growth factor receptor mutation, but not sex and smoking, is independently associated with favorable prognosis of gefitinib-treated patients with lung adenocarcinoma. Cancer Sci 2008;99:303-308
CrossRef | Web of Science | Medline

12

Inoue A, Suzuki T, Fukuhara T, et al. Prospective phase II study of gefitinib for chemotherapy-naive patients with advanced non-small-cell lung cancer with epidermal growth factor receptor gene mutations. J Clin Oncol 2006;24:3340-3346
CrossRef | Web of Science | Medline

13

Asahina H, Yamazaki K, Kinoshita I, et al. A phase II trial of gefitinib as first-line therapy for advanced non-small cell lung cancer with epidermal growth factor receptor mutations. Br J Cancer 2006;95:998-1004
CrossRef | Web of Science | Medline

14

Sutani A, Nagai Y, Udagawa K, et al. Gefitinib for non-small-cell lung cancer patients with epidermal growth factor receptor gene mutations screened by peptide nucleic acid-locked nucleic acid PCR clamp. Br J Cancer 2006;95:1483-1489
CrossRef | Web of Science | Medline

15

Nagai Y, Miyazawa H, Huqun, et al. Genetic heterogeneity of the epidermal growth factor receptor in non-small cell lung cancer cell lines revealed by a rapid and sensitive detection system, the peptide nucleic acid-locked nucleic acid PCR clamp. Cancer Res 2005;65:7276-7282
CrossRef | Web of Science | Medline

16

Tanaka T, Matsuoka M, Sutani A, et al. Frequency of and variables associated with the EGFR mutation and its subtypes. Int J Cancer 2010;126:651-655
CrossRef | Web of Science | Medline

17

Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000;92:205-216
CrossRef | Web of Science | Medline

18

Bell DW, Lynch TJ, Haserlat SM, et al. Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer: molecular analysis of the IDEAL/INTACT gefitinib trials. J Clin Oncol 2005;23:8081-8092
CrossRef | Web of Science | Medline

19

Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649-655
CrossRef | Web of Science | Medline

20

Kobayashi K, Inoue A, Maemondo M, et al. First-line gefitinib versus first-line chemotherapy by carboplatin (CBDCA) plus paclitaxel (TXL) in non-small cell lung cancer (NSCLC) patients (pts) with EGFR mutations: a phase III study (002) by North East Japan Gefitinib Study Group. J Clin Oncol 2009;27:Suppl:411s-411s

21

Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010;11:121-128
CrossRef | Web of Science | Medline

22

Morita S, Okamoto I, Kobayashi K, et al. Combined survival analysis of prospective clinical trials of gefitinib for non-small cell lung cancer with EGFR mutations. Clin Cancer Res 2009;15:4493-4498
CrossRef | Web of Science | Medline

23

Shepherd FA, Pereira JR, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005;353:123-132
Full Text | Web of Science | Medline

24

Thatcher N, Chang A, Parikh P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 2005;366:1527-1537
CrossRef | Web of Science | Medline

25

Rosell R, Moran T, Queralt C, et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 2009;361:958-967
Full Text | Web of Science | Medline

26

Inoue A, Kobayashi K, Usui K, et al. First-line gefitinib for patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations without indication for chemotherapy. J Clin Oncol 2009;27:1394-1400[Erratum, J Clin Oncol 2009;27:3071.]
CrossRef | Web of Science | Medline

27

Inoue A, Saijo Y, Maemondo M, et al. Severe acute interstitial pneumonia and gefitinib. Lancet 2003;361:137-139
CrossRef | Web of Science | Medline

28

Cohen MH, Williams GA, Sridhara R, Chen G, Pazdur R. FDA drug approval summary: gefitinib (ZD1839) (Iressa) tablets. Oncologist 2003;8:303-306
CrossRef | Web of Science | Medline

29

Ando M, Okamoto I, Yamamoto N, et al. Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib. J Clin Oncol 2006;24:2549-2556
CrossRef | Web of Science | Medline

30

Kudoh S, Kato H, Nishiwaki Y, et al. Interstitial lung disease in Japanese patients with lung cancer: a cohort and nested case-control study. Am J Respir Crit Care Med 2008;177:1348-1357
CrossRef | Web of Science | Medline