CANCERS BRONCHIQUES NON A PETITES CELLULES AU STADE AVANCE
ESSAIS RANDOMISES TESTANT LES AGENTS BIOLOGIQUES

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voir aussi inhibiteurs de tyrosine kinase

référence

traitement

n

 

% RO

p

SM

p

O’Brien,

2004 (1)

I. MVP

209

consolidation

 

 

225 j

NS

II. MVP + SRL172 (Mycobacterium vacae)

210

 

223 j

Johnson,

2004 (2)

I. Carbo + paclitaxel

32

1ère ligne

31

 

14,9 m

 

II. Carbo + paclitaxel + Bevacizumab 7,5 mg/kg(AC anti VEGF)

32

22

11,6 m

III. Carbo + paclitaxel + Bevacizumab 15 mg/kg (AC anti VEGF)

35

40

17,7 m

II. Paclitaxel (225) + carboplatine (AUC 6) + gefinitib 250 mg/j

345

30,4

9,8  m

III. Paclitaxel (225) + carboplatine (AUC 6) + placebo

345

28,7

9,9 m

Bissett,

2005 (3)

I. CDDP + gemcitabine + prinomastat

181

1ère ligne

27

0,81

11,5 m

0,82

II. CDDP + gemcitabine + placebo

181

26

10,8 m

Leighl,

2005 (4)

I. Paclitaxel (200) + carboplatine  (AUC 6) +  BMS 275291 (inhibiteur métalloprotéinase de la matrice)

387

1ère ligne

25,8

0,10

8,6 m

0,30

II. Paclitaxel (200) + carboplatine (AUC 6) + placebo

387

33,7

9,2 m

Paz-Ares,

2006 (5)

I. Cisplatine (80) + gemcitabine

328

1ère ligne

35

NS

10,4 m

NS

II. Idem + Aprinocarsen (PKCa antisens)

342

29

10,0 m

Sandler,

2006 (6)

I. Paclitaxel + carboplatine

444

1ère ligne

15

<0,001

10,3 m

0,003

II. Paclitaxel + carboplatine + bévacuzimab

434

35

12,3 m

Gridelli,

2007 (7)

I . CDDP (80) + gemcitabine

121

1ère ligne

26

0,025

44 s

NS

III . CDDP + gemcitabine IVC

II . CDDP + gemcitabine IV+ rofecoxib

119

41

44 s

IV . CDDP + gemcitabine IVC + rofecoxib

Pirker,

2009 (8) I

I. Cisplatine (80) + vinorelbine (6 x)

568

Induction 1ère ligne

29 %

0,01

9,1 m

0,003

II. Idem + Cétuximab (jusqu’à progression)

557

36 %

10,5 m

Reck,

2009 (9) I

2010 (10)

I. Cisplatine + gemcitabine + placebo

347

Induction 1ère ligne

20 %

0,0001

13,1 m

NS

II. Idem + bevacuzimab 7,5 mg/kg

345

34 %

13,6 m

III. Idem + bevacuzimab 15 mg/kg

351

31 %

13,4 m

Lee,

2009 (11), I ?

Entretien après carbo+gemci (x4)

 

Entretien

 

 

 

NS

I. Thalidomide x 2 ans

372

 

8,5 m

II. Placebo

350

 

8,9 m

Goss,

2010 (12), I

I. Carbo-Taxol + cédiranib (inh VEGFr)

126

Induction

38 %

S

 

NS

II. Carbo-Taxol + placebo

125

16 %

 

Lynch,

2010 (13), I

I. Carbo/Taxane + Cetuximab

338

Induction

26 %

S

9,7 m

NS

II. Carbo/Taxane

338

17 %

8,4 m

Lu,

2010 (14), I

I. Chemoradiotherapy + AE-941

188

Stade III

continu

 

 

14.4 m

NS

II. Chemoradiotherapy + placebo

191

 

15,6 m

Hirsh,

2011 (15), I

I. Paclitaxel + carboplatine

420

1ère ligne stade avancé

23 %

0,08

9,8 m

NS

II. + PF-3512676 (Toll-Like Receptor 9 Agonist)

408

28 %

10 m

Lara,

2011 (16), I

I.  Carbo + Paclitaxel

650

1ère ligne stade avancé

25 %

NS

12,7 m

NS

II. + Vadimezan (vascular disrupting)

648

2 5%

 

13,4 m

 

Groe,

2011 (17), I

I. Docetaxel Plus Carboplatin With Celecoxib

281

Stade avancé

38%

0,08

8,2 m

NS

II. Docetaxel Plus Carboplatin With placebo

280

30%

8,2 m

Koch,

2011 (18), I

I. Doublet platine + celecoxib

158

Stade avancé

36 %

0,4

8,9 m

NS

II. Doublet platine + placebo

158

31 %

7,9 m

Manegold,

2012 (19), I

I. CDDP-gemci + PF-3512676 (TLR9 agonist)

416

Stade avancé

32 %

NS

11 m

NS

II. CDDP-Gemci

423

31 %

10,7 m

Hoang,

2012 (20), I

I. RT + carbo-Taxol + thalidomide

271

Stade III

38 %

NS

16 m

NS

II. RT + carbo-Taxol

275

35 %

15 m

Ramlau,

2012 (21) I

I. Docétaxel

457

2ème ligne (échec platine)

8,9 %

S

10,4 m

NS

II. Aflibercept + Docétaxel

456

23,3 %

10,1 m


Références
(1) O'Brien ME, Anderson H, Kaukel E, O'Byrne K, Pawlicki M, von Pawel J, et al. SRL172 (killed Mycobacterium vaccae) in addition to standard chemotherapy improves quality of life without affecting survival, in patients with advanced non-small-cell lung cancer: phase III results. Ann Oncol 2004 Jun;15(6):906-14.
(2) Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, et al. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 2004 Jun 1;22(11):2184-91.
(3) Bissett D, O'Byrne KJ, von Pawel J, Gatzemeier U, Price A, Nicolson M, et al. Phase III study of matrix metalloproteinase inhibitor prinomastat in non-small-cell lung cancer. J Clin Oncol 2005 Feb 1;23(4):842-9.
(4) Leighl NB, Paz-Ares L, Douillard JY, Peschel C, Arnold A, Depierre A, et al. Randomized phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: National Cancer Institute of Canada-Clinical Trials Group Study BR.18. J Clin Oncol 2005 Apr 20;23(12):2831-9.
(5) 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 Mar 20;24(9):1428-34.
(6) Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006 Dec 14;355(24):2542-50.
(7) Gridelli C, Gallo C, Ceribelli A, Gebbia V, Gamucci T, Ciardiello F, et al. Factorial phase III randomised trial of rofecoxib and prolonged constant infusion of gemcitabine in advanced non-small-cell lung cancer: the GEmcitabine-COxib in NSCLC (GECO) study. Lancet Oncol 2007 Jun;8(6):500-12.
(8) Pirker R, Pereira JR, Szczesna A, von PJ, Krzakowski M, Ramlau R, et al. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet 2009 May 2;373(9674):1525-31.
(9) Reck M, von PJ, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, et al. 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 2009 Mar 10;27(8):1227-34.
(10) Reck M, von PJ, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, et al. 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 2010 Sep;21(9):1804-9.
(11) Lee SM, Rudd R, Woll PJ, Ottensmeier C, Gilligan D, Price A, et al. Randomized double-blind placebo-controlled trial of thalidomide in combination with gemcitabine and Carboplatin in advanced non-small-cell lung cancer. J Clin Oncol 2009 Nov 1;27(31):5248-54.
(12) Goss GD, Arnold A, Shepherd FA, Dediu M, Ciuleanu TE, Fenton D, et al. Randomized, double-blind trial of carboplatin and paclitaxel with either daily oral cediranib or placebo in advanced non-small-cell lung cancer: NCIC clinical trials group BR24 study. J Clin Oncol 2010 Jan 1;28(1):49-55.
(13) Lynch TJ, Patel T, Dreisbach L, McCleod M, Heim WJ, Hermann RC, et al. Cetuximab and First-Line Taxane/Carboplatin Chemotherapy in Advanced Non-Small-Cell Lung Cancer: Results of the Randomized Multicenter Phase III Trial BMS099. J Clin Oncol 2010 Feb 20;28(6):911-7.
(14) Lu C, Lee JJ, Komaki R, Herbst RS, Feng L, Evans WK, et al. Chemoradiotherapy with or without AE-941 in stage III non-small cell lung cancer: a randomized phase III trial. J Natl Cancer Inst 2010 Jun 16;102(12):859-65.
(15) Hirsh V, Paz-Ares L, Boyer M, Rosell R, Middleton G, Eberhardt WE, et al. Randomized Phase III Trial of Paclitaxel/Carboplatin With or Without PF-3512676 (Toll-Like Receptor 9 Agonist) As First-Line Treatment for Advanced Non-Small-Cell Lung Cancer. J Clin Oncol 2011 Jul 1;29(19):2667-74.
(16) Lara PN, Jr., Douillard JY, Nakagawa K, von PJ, McKeage MJ, Albert I, et al. Randomized Phase III Placebo-Controlled Trial of Carboplatin and Paclitaxel With or Without the Vascular Disrupting Agent Vadimezan (ASA404) in Advanced Non-Small-Cell Lung Cancer. J Clin Oncol 2011 Aug 1;29(22):2965-71.
(17) Groen HJ, Sietsma H, Vincent A, Hochstenbag MM, Van Putten JW, van den BA, et al. Randomized, Placebo-Controlled Phase III Study of Docetaxel Plus Carboplatin With Celecoxib and Cyclooxygenase-2 Expression As a Biomarker for Patients With Advanced Non-Small-Cell Lung Cancer: The NVALT-4 Study. J Clin Oncol 2011 Nov 10;29(32):4320-6.
(18) Koch A, Bergman B, Holmberg E, Sederholm C, Ek L, Kosieradzki J, et al. Effect of celecoxib on survival in patients with advanced non-small cell lung cancer: a double blind randomised clinical phase III trial (CYCLUS study) by the Swedish Lung Cancer Study Group. Eur J Cancer 2011 Jul;47(10):1546-55.
(19) Manegold C, Van Zandwijk N., Szczesna A, Zatloukal P, Au JS, Blasinska-Morawiec M, et al. A phase III randomized study of gemcitabine and cisplatin with or without PF-3512676 (TLR9 agonist) as first-line treatment of advanced non-small-cell lung cancer. Ann Oncol 2012 Jan;23(1):72-7.
(20) Hoang T, Dahlberg SE, Schiller JH, Mehta MP, Fitzgerald TJ, Belinsky SA, et al. Randomized Phase III Study of Thoracic Radiation in Combination With Paclitaxel and Carboplatin With or Without Thalidomide in Patients With Stage III Non-Small-Cell Lung Cancer: The ECOG 3598 Study. J Clin Oncol 2012 Feb 20;30(6):616-22.
(21) Ramlau R, Gorbunova V, Ciuleanu TE, Novello S, Ozguroglu M, Goksel T, et al. Aflibercept and Docetaxel Versus Docetaxel Alone After Platinum Failure in Patients With Advanced or Metastatic Non-Small-Cell Lung Cancer: A Randomized, Controlled Phase III Trial. J Clin Oncol 2012 Oct 10;30(29):3640-7.


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