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Cancer Chemotherapy and Pharmacology

, Volume 68, Issue 1, pp 1–15 | Cite as

Review on clinical trials of targeted treatments in malignant mesothelioma

  • Jan Nyrop Jakobsen
  • Jens Benn Sørensen
Mini Review

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.

Keywords

Malignant mesothelioma Malignant pleural mesothelioma Targeted treatments Tyrosine kinase inhibitors 

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

Notes

Conflicts of interest

None.

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© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Department of OncologyFinsencentreCopenhagenDenmark
  2. 2.RigshospitaletCopenhagenDenmark

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