Skip to main content

Advertisement

Log in

Review on clinical trials of targeted treatments in malignant mesothelioma

  • Mini Review
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Malignant mesothelioma (MM) is an aggressive tumor of the serosal surfaces with a poor prognosis. Advances in the understanding of tumor biology have led to the development of several targeted treatments, which have been evaluated in clinical trials. This article is a comprehensive review of all clinical trials evaluating the effect of targeted treatments in MM.

Methods

An extensive literature search was performed in January 2011 using pubmed and medline. No constraints on publication date were applied.

Results

Thirty-two trials exploring 17 different targeted agents in MM were found. Treatment in first- and second-line targeted agents induced response rates ranging from 0–14% and 0–16%, respectively. The tyrosine kinase inhibitor sunitinib induced partial response in 10% and stable disease in 66% of MPM patients as second-line treatment. A preliminary analysis of a phase II/III trial suggests that addition of bevacizumab to pemetrexed and cisplatin first-line treatment significantly improves disease control (CR + PR + SD) in the bevacizumab arm (73.5%) compared with treatment with pemetrexed and cisplatin without bevacizumab (43.2%) (P = 0.010). Another phase II trial did not observe any significant clinical benefit of adding of bevacizumab to gemcitabine and cisplatin.

Conclusions

Disease stabilization is reported in some patients with several targeted treatments and might be beneficial in subgroups of patients or in combination with classic chemotherapy. None of the hitherto explored targeted treatments can currently be recommended as standard treatment in MM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ABL:

Abelson murine leukemia viral oncogene homolog

AKT:

A member of the non-specific serine/threonine-protein kinase family

ALK:

Anaplastic lymphoma kinase

BCR:

Breakpoint cluster region

CALGB:

Cancer and leukemia group B

c-KIT:

V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog

CML:

Chronic myeloid leukemia

CR:

Complete response

EGF:

Endothelial growth factor

EGFR:

Endothelial growth factor receptor

EML4:

Echinoderm microtubule-associated protein-like 4

EPP:

Extrapleural pneumectomy

FDG-PET:

Fludeoxyglucose(18F) positron emission tomography

GIST:

Gastrointestinal stromal tumor

HDAC:

Histone deacetylase

HDACi:

Histone deacetylase inhibitor

IFP:

Interstitial fluid pressure

IGF-1:

Insulin-like growth factor 1

KDR:

Kinase insert domain receptor

MM:

Malignant mesothelioma

MPM:

Malignant pleural mesothelioma

mTOR:

Mammalian target of rapamycin

NGR:

Asparagine–glycine–arginine

hTNF:

Human tumor necrosis factor-alpha

OS:

Overall survival

PD:

Progression disease

PDGF:

Platelet derived growth factor

PDGFR:

Platelet derived growth factor receptor

P/D:

Pleurectomy/decortication

PFS:

Progression free survival

PI3K:

Phosphatidylinositol 3-kinase

PR:

Partial response

RNA:

Ribonucleic acid

SRC:

Sarcoma

SD:

Stable disease

TGF-alpha:

Tumor growth factor-alpha

TKI:

Tyrosine kinase inhibitor

VEGF:

Vascular endothelial growth factor

VEGFR:

Vascular endothelial growth factor receptor

References

  1. Steele JPC, Klabatsa A, Fennell DA, Palläska A, Sheaff MT, Evans MT et al (2005) Prognostic factors in mesothelioma. Lung Cancer 49(Suppl 1):S49–S52

    Article  PubMed  Google Scholar 

  2. Yates DH, Corrin B, Stidolph PN, Browne K (1997) Malignant mesothelioma in south east England: clinicopathological experience of 272 cases. Thorax 52(6):507–512

    Article  PubMed  CAS  Google Scholar 

  3. Vogelzang NJ, Porta C, Mutti L (2005) New agents in the management of advanced mesothelioma. Semin Oncol 32(3):336–350

    Article  PubMed  CAS  Google Scholar 

  4. Sørensen JB, Frank H, Palshof T (2008) Cisplatin and vinorelbine first-line chemotherapy in non-resectable malignant pleural mesothelioma. Br J Cancer 99(1):44–50

    Article  PubMed  Google Scholar 

  5. Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P et al (2003) Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 21(14):2636–2644

    Article  PubMed  CAS  Google Scholar 

  6. Ceresoli GL, Zucali PA, Gianoncelli L, Lorenzi E, Santoro A (2010) Second-line treatment for malignant pleural mesothelioma. Cancer Treat Rev 36(1):24–32

    Article  PubMed  Google Scholar 

  7. Edwards JG, Cox G, Andi A, Jones JL, Walker RA, Waller DA et al (2001) Angiogenesis is an independent prognostic factor in malignant mesothelioma. Br J Cancer 85(6):863–868

    Article  PubMed  CAS  Google Scholar 

  8. Filiberti R, Marroni P, Neri M, Ardizzoni A, Betta PG, Cafferata MA et al (2005) Serum PDGF-AB in pleural mesothelioma. Tumour Biol 26(5):221–226

    Article  PubMed  CAS  Google Scholar 

  9. Arber DA, Tamayo R, Weiss LM (1998) Paraffin section detection of the c-kit gene product (CD117) in human tissues: value in the diagnosis of mast cell disorders. Hum Pathol 29(5):498–504

    Article  PubMed  CAS  Google Scholar 

  10. Millward M, Parnis F, Byrne M, Powell A, Dunleavey R, Lynch K et al (2003) Phase II trial of imatinib mesylate in patients with advanced pleural mesothelioma. Am J Clin Oncol 22:912

    Google Scholar 

  11. Mathy A, Baas P, Dalesio O, van Zandwijk N (2005) Limited efficacy of imatinib mesylate in malignant mesothelioma: a phase II trial. Lung Cancer 50(1):83–86

    Article  PubMed  Google Scholar 

  12. Porta C, Mutti L, Tassi G (2007) Negative results of an Italian Group for Mesothelioma (G.I.Me.) pilot study of single-agent imatinib mesylate in malignant pleural mesothelioma. Cancer Chemother Pharmacol 59(1):149–150

    Article  PubMed  Google Scholar 

  13. Villano J, Husain A, Stadler M, Hanson L, Vogelzang N, Kindler H et al (2004) A Phase II trial of imatinib mesylate in patients (pts) with malignant mesothelioma (MM). J Clin Oncol 22:14

    Google Scholar 

  14. Bertino P, Porta C, Barbone D, Germano S, Busacca S, Pinato S et al (2007) Preliminary data suggestive of a novel translational approach to mesothelioma treatment: imatinib mesylate with gemcitabine or pemetrexed. Thorax 62(8):690–695

    Article  PubMed  Google Scholar 

  15. Pietras K, Rubin K, Sjöblom T, Buchdunger E, Sjöquist M, Heldin CH et al (2002) Inhibition of PDGF receptor signaling in tumor stroma enhances antitumor effect of chemotherapy. Cancer Res 62(19):5476–5484

    PubMed  CAS  Google Scholar 

  16. Ali Y, Lin Y, Gharibo MM, Gounder MK, Stein MN, Lagattuta TF et al (2007) Phase I and pharmacokinetic study of imatinib mesylate (Gleevec) and gemcitabine in patients with refractory solid tumors. Clin Cancer Res 13(19):5876–5882

    Article  PubMed  CAS  Google Scholar 

  17. Cisplatin, pemetrexed, and imatinib mesylate in malignant mesothelioma. http://www.clinicaltrials.gov

  18. A Phase II study of the association of Glivec® Plus Gemzar® in patients with unresectable, refractory, malignant mesothelioma. http://www.clinicaltrials.gov

  19. Tsao AS, He D, Saigal B, Liu S, Lee JJ, Bakkannagari S et al (2007) Inhibition of c-Src expression and activation in malignant pleural mesothelioma tissues leads to apoptosis, cell cycle arrest, and decreased migration and invasion. Mol Cancer Ther 6(7):1962–1972

    Article  PubMed  CAS  Google Scholar 

  20. Tsao A, Mistuba I, Mehren J (2010) Evaluation of Src Tyr419 as a predictive biomarker in a neoadjuvant trial using dasatinib in resectable malignant pleural mesothelioma. Am J Clin Oncol 25:15

    Google Scholar 

  21. Dudek A, Pang H, Kratzke A (2010) A phase II study of dasatinib (D) in patients (pts) with previously treated malignant mesothelioma. J Natl Cancer Inst 28:15

    Google Scholar 

  22. Dasatinib in treating patients with previously treated malignant mesothelioma. http://www.clinicaltrials.gov

  23. Irshad S, Popat S, Shah R (2010) A phase II study of sorafenib in malignant mesothelioma with pharmacodynamic imaging using 18fdg-PET. J Natl Cancer Inst 28:15

    Google Scholar 

  24. Dubey S, Jänne PA, Krug L, Pang H, Wang X, Heinze R et al (2010) A phase II study of sorafenib in malignant mesothelioma: results of Cancer and Leukemia Group B 30307. J Thorac Oncol 5(10):1655–1661

    Article  PubMed  Google Scholar 

  25. Novak A, Millward M, Francis R (2010) Final results of a phase II study of sunitinib as second-line therapy in malignant pleural mesothelioma. J Clin Oncol 28:15

    Article  Google Scholar 

  26. Yarden Y (2001) The EGFR family and its ligands in human cancer. signalling mechanisms and therapeutic opportunities. Eur J Cancer 37(Suppl 4):S3–S8

    Article  PubMed  CAS  Google Scholar 

  27. Destro A, Ceresoli G, Falleni M (2006) EGFR overexpression in malignant pleural mesothelioma. An immunohistochemical and molecular study with clinicopathological correlations. Lung Cancer 51:207–215

    CAS  Google Scholar 

  28. Govindan R, Kratzke RA, Herndon JE, Niehans GA, Vollmer R, Watson D et al (2005) Gefitinib in patients with malignant mesothelioma: a phase II study by the Cancer and Leukemia Group B. Clin Cancer Res 11(6):2300–2304

    Article  PubMed  CAS  Google Scholar 

  29. Lee C, Anderson H, Martins H (2008) A phase II trial of gefitinib in patients with malignant pleural mesothelioma (MPM). J Clin Oncol 26:15

    Google Scholar 

  30. Garland LL, Rankin C, Gandara DR, Rivkin SE, Scott KM, Nagle RB et al (2007) Phase II study of erlotinib in patients with malignant pleural mesothelioma: a Southwest Oncology Group Study. J Clin Oncol 25(17):2406–2413

    Article  PubMed  CAS  Google Scholar 

  31. Jackman DM, Kindler HL, Yeap BY, Fidias P, Salgia R, Lucca J et al (2008) Erlotinib plus bevacizumab in previously treated patients with malignant pleural mesothelioma. Cancer 113(4):808–814

    Article  PubMed  CAS  Google Scholar 

  32. Cortese J, Gowda A, Wali A, Eliason J, Pass H, Everson R et al (2006) Common EGFR mutations conferring sensitivity to gefitinib in lung adenocarcinoma are not prevalent in human malignantmesothelioma. Int J Cancer 118(2):521–522

    Article  PubMed  CAS  Google Scholar 

  33. Ohta Y, Shridhar V, Bright RK, Kalemkerian GP, Du W, Carbone M et al (1999) VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours. Br J Cancer 81(1):54–61

    Article  PubMed  CAS  Google Scholar 

  34. Dowell J, Kindler H (2005) Antiangiogenic therapies for mesothelioma. Hematol Oncol Clin North Am 19:1137–1145

    Article  PubMed  Google Scholar 

  35. Yasumitsu A, Tabata C, Tabata R, Hirayama N, Murakami A, Yamada S et al (2010) Clinical significance of serum vascular endothelial growth factor in malignant pleural mesothelioma. J Thorac Oncol 5(4):479–483

    Article  PubMed  Google Scholar 

  36. Strizzi L, Catalano A, Vianale G, Orecchia S, Casalini A, Tassi G et al (2001) Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma. J Pathol 193(4):468–475

    Article  PubMed  CAS  Google Scholar 

  37. Karrison T, Kindler HL, Gandara DR (2007) S374 Final analysis of a multi-center, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin (GC) plus bevacizumab (B) or placebo (P) in patients with malignant mesothelioma. J Thorac Oncol 2:8

    Google Scholar 

  38. Dowell J, Gerber D, Dunphy F (2010) Association of hypertension (HTN) and clinical outcome in a phase II trial of cisplatin (C), pemetrexed (P), and bevacizumab (B) in patients (pts) with untreated malignant mesothelioma. J Clin Oncol 28:15

    Article  Google Scholar 

  39. Zalcman G, Margery J, Scherpereel A (2010) IFCT-GFPC-0701 MAPS trial, a multicenter randomized phase II/III trial of pemetrexed-cisplatin with or without bevacizumab in patients with malignant pleural mesothelioma. J Clin Oncol 28:15

    Article  Google Scholar 

  40. Jahan T, Gu L, Wang X (2006) Vatalanib (V) for patients with previously untreated advanced malignant mesothelioma (MM): a phase II study by the Cancer and Leukemia Group B (CALGB 30107). J Clin Oncol 24(18):7081

    Google Scholar 

  41. Mitchell CL, O’Connor JPB, Roberts C, Watson Y, Jackson A, Cheung S, et al. (2010) A two-part Phase II study of cediranib in patients with advanced solid tumours: the effect of food on single-dose pharmacokinetics and an evaluation of safety, efficacy and imaging pharmacodynamics. Cancer Chemother Pharmacol

  42. Drevs J, Siegert P, Medinger M, Mross K, Strecker R, Zirrgiebel U et al (2007) Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors. J Clin Oncol 25(21):3045–3054

    Article  PubMed  CAS  Google Scholar 

  43. Matulonis UA, Berlin S, Ivy P, Tyburski K, Krasner C, Zarwan C et al (2009) Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer. J Clin Oncol 27(33):5601–5606

    Article  PubMed  CAS  Google Scholar 

  44. Garland L, Chansky K, Wosniak A (2009) A phase II study of novel oral antiangiogenic agent AZD2171 (NSC-732208) in malignant pleural mesothelioma. J Clin Oncol 27:15

    Article  Google Scholar 

  45. Pemetrexed disodium and cisplatin with or without cediranib maleate in treating patients with malignant pleural mesothelioma. http://www.clinicaltrials.gov

  46. Kindler H, Vogelzang J, Chien K (2001) SU5416 in malignant mesothelioma: a University of Chicago consortium study. J Clin Oncol 20:341

    Google Scholar 

  47. Morabito A, De Maio E, Di Maio M, Normanno N, Perrone F (2006) Tyrosine kinase inhibitors of vascular endothelial growth factor receptors in clinical trials: current status and future directions. Oncologist 11(7):753–764

    Article  PubMed  CAS  Google Scholar 

  48. Baas P, Boogerd W, Dalesio O, Haringhuizen A, Custers F, van Zandwijk N et al (2005) Thalidomide in patients with malignant pleural mesothelioma. Lung Cancer 48(2):291–296

    Article  PubMed  Google Scholar 

  49. Pavlakis N, Abraham R, Harvie R (2003) Thalidomide alone or in combination with cisplatin/Gemcitabine in malignant pleural mesothelioma (MM); Interim results from two parallel non randomized phase II studies. Lung Cancer 41(2):11

    Article  Google Scholar 

  50. MATES: Maintenance Thalidomide in Mesothelioma Patients. A phase III trial of anti-angiogenic agent Thalidomide in patients with malignant pleural mesothelioma after first line chemotherapy. http://www.anzctr.org.au/ACTRN12609000141246.aspx

  51. Ramos-Nino ME, Testa JR, Altomare DA, Pass HI, Carbone M, Bocchetta M et al (2006) Cellular and molecular parameters of mesothelioma. J Cell Biochem 98(4):723–734

    Article  PubMed  CAS  Google Scholar 

  52. Altomare DA, You H, Xiao GH, Ramos-Nino ME, Skele KL, De Rienzo A et al (2005) Human and mouse mesotheliomas exhibit elevated AKT/PKB activity, which can be targeted pharmacologically to inhibit tumor cell growth. Oncogene 24(40):6080–6089

    Article  PubMed  CAS  Google Scholar 

  53. Raymond E, Alexandre J, Faivre S, Vera K, Materman E, Boni J et al (2004) Safety and pharmacokinetics of escalated doses of weekly intravenous infusion of CCI-779, a novel mTOR inhibitor, in patients with cancer. J Clin Oncol 22(12):2336–2347

    Article  PubMed  CAS  Google Scholar 

  54. Hartman ML, Esposito JM, Yeap BY, Sugarbaker DJ (2010) Combined treatment with cisplatin and sirolimus to enhance cell death in human mesothelioma. J Thorac Cardiovasc Surg 139(5):1233–1240

    Article  PubMed  CAS  Google Scholar 

  55. Everolimus (RAD001) for the Treatment of Malignant Pleural Mesothelioma With Merlin/NF2 Loss as a Biomarker to Predict Sensitivity. http://www.clinicaltrials.gov

  56. Everolimus in Treating Patients With Pleural Malignant Mesothelioma That Cannot Be Removed By Surgery. http://www.clinicaltrials.gov

  57. Chang K, Pai LH, Pass H, Pogrebniak HW, Tsao MS, Pastan I et al (1992) Monoclonal antibody K1 reacts with epithelial mesothelioma but not with lung adenocarcinoma. Am J Surg Pathol 16(3):259–268

    Article  PubMed  CAS  Google Scholar 

  58. Shaw DR, Muminova ZE, Strong TV (2004) Mesothelin: a new target for immunotherapy. Clin Cancer Res 10(24):8751 (author reply 8752)

    Article  PubMed  Google Scholar 

  59. Chang K, Pastan I (1996) Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers. Proc Natl Acad Sci USA 93(1):136–140

    Article  PubMed  CAS  Google Scholar 

  60. Hassan R, Bera T, Pastan I (2004) Mesothelin: a new target for immunotherapy. Clin Cancer Res 10(12 Pt 1):3937–3942

    Article  PubMed  CAS  Google Scholar 

  61. Hassan R, Schweizer C, Lu KF, Schuler B, Remaley AT, Weil SC et al (2010) Inhibition of mesothelin-CA-125 interaction in patients with mesothelioma by the anti-mesothelin monoclonal antibody MORAb-009: Implications for cancer therapy. Lung Cancer 68(3):455–459

    Article  PubMed  Google Scholar 

  62. Laheru D, Cohen J, Phillips M (2008) A phase I study of MORab-009, a monoclonal antibody against mesothelin, in mesothelioma, pancreatic and ovarian cancer. J Clin Oncol 26:15

    Google Scholar 

  63. An Efficacy Study of MORAb-009 Amatuximab in Subjects With Pleural Mesothelioma. http://www.clinicaltrials.gov

  64. Mikulski SM, Costanzi JJ, Vogelzang NJ, McCachren S, Taub RN, Chun H et al (2002) Phase II trial of a single weekly intravenous dose of ranpirnase in patients with unresectable malignant mesothelioma. J Clin Oncol 20(1):274–281

    Article  PubMed  CAS  Google Scholar 

  65. Reck M, Krzakowski M, Jassem J (2009) Randomized, multicenter phase III study of ranpirnase plus doxorubicin (DOX) versus DOX in patients with unresectable malignant mesothelioma (MM). J Clin Oncol 27:15

    Article  Google Scholar 

  66. Mittelman A, Puccio C, Gafney E, Coombe N, Singh B, Wood D et al (1992) A phase I pharmacokinetic study of recombinant human tumor necrosis factor administered by a 5-day continuous infusion. Invest New Drugs 10(3):183–190

    Article  PubMed  CAS  Google Scholar 

  67. Creaven PJ, Brenner DE, Cowens JW, Huben RP, Wolf RM, Takita H et al (1989) A phase I clinical trial of recombinant human tumor necrosis factor given daily for five days. Cancer Chemother Pharmacol 23(3):186–191

    Article  PubMed  CAS  Google Scholar 

  68. Lejeune FJ, Liénard D, Matter M, Rüegg C (2006) Efficiency of recombinant human TNF in human cancer therapy. Cancer Immun 6:6

    PubMed  Google Scholar 

  69. Gregorc V, Zucali PA, Santoro A, Ceresoli GL, Citterio G, De Pas TM et al (2010) Phase II study of asparagine-glycine-arginine-human tumor necrosis factor alpha, a selective vascular targeting agent, in previously treated patients with malignant pleural mesothelioma. J Clin Oncol 28(15):2604–2611

    Article  PubMed  CAS  Google Scholar 

  70. NGR015: Study in Second Line for Patient with Advanced Malignant Pleural Mesothelioma Pretreated with Pemetrexed. http://www.clinicaltrials.gov

  71. Marks PA, Richon VM, Miller T, Kelly WK (2004) Histone deacetylase inhibitors. Adv Cancer Res 91:137–168

    Article  PubMed  CAS  Google Scholar 

  72. Frew AJ, Johnstone RW, Bolden JE (2009) Enhancing the apoptotic and therapeutic effects of HDAC inhibitors. Cancer Lett 280(2):125–133

    Article  PubMed  CAS  Google Scholar 

  73. Kelly WK, O’Connor OA, Krug LM, Chiao JH, Heaney M, Curley T et al (2005) Phase I study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in patients with advanced cancer. J Clin Oncol 23(17):3923–3931

    Article  PubMed  CAS  Google Scholar 

  74. Ramalingam SS, Parise RA, Ramanathan RK, Ramananthan RK, Lagattuta TF, Musguire LA et al (2007) Phase I and pharmacokinetic study of vorinostat, a histone deacetylase inhibitor, in combination with carboplatin and paclitaxel for advanced solid malignancies. Clin Cancer Res 13(12):3605–3610

    Article  PubMed  CAS  Google Scholar 

  75. Suberoylanilide Hydroxamic Acid (Vorinostat, MK-0683) Versus Placebo in Advanced Malignant Pleural Mesothelioma (0683-014 AM5, EXT1). http://www.clinicaltrials.gov

  76. Ramalingam SS, Belani CP, Ruel C, Frankel P, Gitlitz B, Koczywas M et al (2009) Phase II study of belinostat (PXD101), a histone deacetylase inhibitor, for second line therapy of advanced malignant pleural mesothelioma. J Thorac Oncol 4(1):97–101

    Article  PubMed  Google Scholar 

  77. Scherpereel A, Berghmans T, Lafitte JJ, Colinet B, Richez M, Bonduelle Y et al (2011) Valproate-doxorubicin: promising therapy for progressing mesothelioma. A phase II study. Eur Respir J 37(1):129–135

    Article  PubMed  CAS  Google Scholar 

  78. Shapiro GI, Tibes R, Gordon MS, Wong BY, Eder JP, Borad MJ et al (2011) Phase I Studies of CBP501, a G2 checkpoint abrogator, as monotherapy and in combination with cisplatin in patients with advanced solid tumors. Clin Cancer Res

  79. Kai K, D’Costa S, Sills RC, Kim Y (2009) Inhibition of the insulin-like growth factor 1 receptor pathway enhances the antitumor effect of cisplatin in human malignant mesothelioma cell lines. Cancer Lett 278(1):49–55

    Article  PubMed  CAS  Google Scholar 

  80. Pazopanib in Treating Patients With Malignant Pleural Mesothelioma. http://www.clinicaltrials.gov

  81. Axitinib in Malignant Mesothelioma (N08CPA). http://www.clinicaltrials.gov

  82. Sartore-Bianchi A, Gasparri F, Galvani A, Nici L, Darnowski JW, Barbone D et al (2007) Bortezomib inhibits nuclear factor-kappaB dependent survival and has potent in vivo activity in mesothelioma. Clin Cancer Res 13(19):5942–5951

    Article  PubMed  CAS  Google Scholar 

  83. Bortezomib in Treating Patients With Malignant Pleural Mesothelioma. http://www.clinicaltrials.gov

  84. Gordon GJ, Mani M, Maulik G, Mukhopadhyay L, Yeap BY, Kindler HL et al (2008) Preclinical studies of the proteasome inhibitor bortezomib in malignant pleural mesothelioma. Cancer Chemother Pharmacol 61(4):549–558

    Article  PubMed  CAS  Google Scholar 

  85. Bortezomib and Cisplatin as First-Line Therapy in Treating Patients With Malignant Mesothelioma. http://www.clinicaltrials.gov

  86. A Study of Cetuximab Combined With Cisplatin or Carboplatin/Pemetrexed as First Line Treatment in Patients With Malignant Pleural Mesothelioma. (MesoMab). http://www.clinicaltrials.gov

  87. Phase I Dose-Escalation Study Of Azacitidine In Combination With Temozolomide. http://www.clinicaltrials.gov

  88. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355(24):2542–2550

    Article  PubMed  CAS  Google Scholar 

  89. Johnson D, Fehrenbacher L, Novotny W (2004) 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 22:2184–2191

    Article  PubMed  CAS  Google Scholar 

  90. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350(23):2335–2342

    Article  PubMed  CAS  Google Scholar 

  91. Frederick PJ, Straughn JM, Alvarez RD, Buchsbaum DJ (2009) Preclinical studies and clinical utilization of monoclonal antibodies in epithelial ovarian cancer. Gynecol Oncol 113(3):384–390

    Article  PubMed  CAS  Google Scholar 

  92. Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA et al (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357(26):2666–2676

    Article  PubMed  CAS  Google Scholar 

  93. Zuniga RM, Torcuator R, Jain R, Anderson J, Doyle T, Ellika S et al (2009) Efficacy, safety and patterns of response and recurrence in patients with recurrent high-grade gliomas treated with bevacizumab plus irinotecan. J Neurooncol 91(3):329–336

    Article  PubMed  CAS  Google Scholar 

  94. Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H et al (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362(25):2380–2388

    Article  PubMed  CAS  Google Scholar 

  95. Whitehead J (2004) Stopping clinical trials by design. Nat Rev Drug Discov 3(11):973–977

    Article  PubMed  CAS  Google Scholar 

  96. Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ et al (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347(7):472–480

    Article  PubMed  CAS  Google Scholar 

  97. Mol CD, Dougan DR, Schneider TR, Skene RJ, Kraus ML, Scheibe DN et al (2004) Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase. J Biol Chem 279(30):31655–31663

    Article  PubMed  CAS  Google Scholar 

  98. Byrne MJ, Nowak AK (2004) Modified RECIST criteria for assessment of response in malignant pleural mesothelioma. Ann Oncol 15(2):257–260

    Article  PubMed  CAS  Google Scholar 

  99. Alavi A (2010) Current evidence base of FDG-PET/CT imaging in the clinical management of malignant pleural mesothelioma: emerging significance of image segmentation and global disease assessment. Mol Imaging Biol [Epub ahead of print]

  100. Federal Drug Administration (2007) Guidance for industry. Clinical trials endpoints for the approval of cancer drugs and biologics. UD Department of Health and Human Services, Rockville

  101. Di Leo A, Bleiberg H, Buyse M (2003) Overall survival is not a realistic end point for clinical trials of new drugs in advanced solid tumors: a critical assessment based on recently reported phase III trials in colorectal and breast cancer. J Clin Oncol 21(10):2045–2047

    Article  PubMed  Google Scholar 

  102. Francart J, Legrand C, Sylvester R, Van Glabbeke M, van Meerbeeck JP, Robert A et al (2006) Progression-free survival rate as primary end point for phase II cancer clinical trials: application to mesothelioma—the EORTC Lung Cancer Group. J Clin Oncol 24(19):3007–3012

    Article  PubMed  Google Scholar 

  103. Haas-Kogan DA, Prados MD, Tihan T, Eberhard DA, Jelluma N, Arvold ND et al (2005) Epidermal growth factor receptor, protein kinase B/Akt, and glioma response to erlotinib. J Natl Cancer Inst 97(12):880–887

    Article  PubMed  CAS  Google Scholar 

  104. Bang Y, Kwak L, Shaw A (2010) Clinical activity of the oral ALK inhibitor PF-02341066 in ALK-positive patients with non-small cell lung cancer (NSCLC). J Clin Oncol 28:18

    Google Scholar 

Download references

Conflicts of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jan Nyrop Jakobsen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jakobsen, J.N., Sørensen, J.B. Review on clinical trials of targeted treatments in malignant mesothelioma. Cancer Chemother Pharmacol 68, 1–15 (2011). https://doi.org/10.1007/s00280-011-1655-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-011-1655-3

Keywords

Navigation