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Clinical Development Of New Formulations Of Cytotoxics In Solid Tumors

H. Azim, A. Awada
Published 2012 · Medicine

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Purpose of review To discuss the clinical development of new formulations of old cytotoxic agents and highlight the value of adopting this strategy. Recent findings Several drugs are currently in clinical development with high potential in improving clinical outcomes compared with their older counterparts. We emphasize on the results of four of these agents, each belonging to a known group of cytotoxics namely amrubicin, EndoTAG-1, pralatrexate and NKTR-102. Each has shown promising results that have the potential in addressing some limitations that have been observed with the ‘earlier generation’ agents. Summary Improvement in drug development strategies and the appreciation of the mechanisms of action and resistance of the cytotoxic agents currently available in the clinic open the door for developing agents that have the potential of improving clinical outcomes with better safety profiles. It is important to adopt innovative clinical trials designs integrating molecular markers in early clinical development in order to identify the subgroups of patients who would derive the maximal benefit of these novel agents.
This paper references
10.1200/JCO.2006.08.4145
Phase II trial of amrubicin for treatment of refractory or relapsed small-cell lung cancer: Thoracic Oncology Research Group Study 0301.
Sayaka Onoda (2006)
10.1002/ijc.24846
Vascular targeting by EndoTAG™‐1 enhances therapeutic efficacy of conventional chemotherapy in lung and pancreatic cancer
M. Eichhorn (2010)
10.1016/0305-7372(89)90011-X
Liposomes as carriers of antitumor agents: toward a clinical reality.
R. Pérez-Soler (1989)
Significant antitumor activity in a randomized phase 2 study comparing two schedules of NKTR-102 in patients with pretreated metastatic breast cancer
A Awada (2011)
10.1111/j.1349-7006.1998.tb00496.x
In vivo Efficacy and Tumor‐selective Metabolism of Amrubicin to Its Active Metabolite
Toshihiro Noguchi (1998)
10.1097/CAD.0B013E328011A547
Treatment options for relapsed small-cell lung cancer
H. Azim (2007)
10.1200/jco.2009.27.15_suppl.4526
Cationic liposomal paclitaxel in combination with gemcitabine in patients with advanced pancreatic cancer: A phase II trial.
M. Löhr (2009)
10.1200/JCO.2010.31.2231
Multifactorial approach to predicting resistance to anthracyclines.
C. Desmedt (2011)
10.1146/ANNUREV.NUTR.19.1.91
Carrier-mediated membrane transport of folates in mammalian cells.
F. Sirotnak (1999)
10.1016/S0959-8049(01)00171-X
Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation.
H. Gelderblom (2001)
10-propargyl-10-deazaaminopterin: an antifolate with activity in patients with previously treated non-small cell lung cancer.
L. Krug (2003)
10.1158/1078-0432.CCR-07-4738
Paclitaxel Encapsulated in Cationic Liposomes Increases Tumor Microvessel Leakiness and Improves Therapeutic Efficacy in Combination with Cisplatin
S. Strieth (2008)
10.1200/JCO.2011.29.15_SUPPL.7000
Randomized phase III trial of amrubicin versus topotecan (Topo) as second-line treatment for small cell lung cancer (SCLC).
R. Jotte (2011)
10.1016/j.ejca.2011.05.020
Randomised phase II study of amrubicin as single agent or in combination with cisplatin versus cisplatin etoposide as first-line treatment in patients with extensive stage small cell lung cancer - EORTC 08062.
M. O'brien (2011)
Results of the first randomized phase II study of cationic liposomal paclitaxel (ENDOTAG-1) targeting tumor endothelial cells in advanced triple-negative breast cancer (TNBC)
A Awada (2010)
10.1093/jjco/hyr065
Amrubicin monotherapy for patients with previously treated advanced large-cell neuroendocrine carcinoma of the lung.
H. Yoshida (2011)
10.1200/JCO.2010.29.8851
Randomized phase II trial of single-agent amrubicin or topotecan as second-line treatment in patients with small-cell lung cancer sensitive to first-line platinum-based chemotherapy.
R. Jotte (2011)
10.1002/ijc.23088
Tumor‐selective vessel occlusions by platelets after vascular targeting chemotherapy using paclitaxel encapsulated in cationic liposomes
S. Strieth (2008)
10.1002/1097-4652(200009)184:3<364::AID-JCP11>3.0.CO;2-N
Contrasting effects of oncogene expression on two carrier‐mediated systems internalizing folate compounds in Fisher rat 3T3 cells
J. Kühnel (2000)
10.1200/JCO.2010.28.15_SUPPL.5013
Phase II study of NKTR-102 in women with platinum-resistant/refractory ovarian cancer.
I. Vergote (2010)
10.1172/JCI965
Cationic liposomes target angiogenic endothelial cells in tumors and chronic inflammation in mice.
G. Thurston (1998)
10.1056/nejmoa011795
CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma.
B. Coiffier (2002)
10.1007/s00280-009-1151-1
Relationship of mRNA expressions of RanBP2 and topoisomerase II isoforms to cytotoxicity of amrubicin in human lung cancer cell lines
Y. Horio (2009)
10.1038/nrclinonc.2009.37
Reasons for response differences seen in the V15-32, INTEREST and IPASS trials
N. Saijo (2009)
10.1200/JCO.2009.26.7682
Phase II study of amrubicin as second-line therapy in patients with platinum-refractory small-cell lung cancer.
D. Ettinger (2010)
10.1056/NEJMoa0810699
Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.
T. Mok (2009)
Phase I and pharmacokinetic study of 10-propargyl-10-deazaaminopterin, a new antifolate.
L. Krug (2000)
10.1200/JCO.2010.29.9024
Pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma: results from the pivotal PROPEL study.
O. O’Connor (2011)
10.1111/j.1349-7006.1998.tb00497.x
Tumor‐selective Distribution of an Active Metabolite of the 9‐Aminoanthracycline Amrubicin
Toshihiro Noguchi (1998)
10.1093/annonc/mdr300
Vascular and pharmacokinetic effects of EndoTAG-1 in patients with advanced cancer and liver metastasis.
U. Fasol (2012)
10.1097/JTO.0b013e3181c07c6c
Phase II Trial of Amrubicin for Second-Line Treatment of Advanced Non-small Cell Lung Cancer: Results of the West Japan Thoracic Oncology Group Trial (WJTOG0401)
Hiroyasu Kaneda (2010)
10.1634/theoncologist.2008-0232
The differential efficacy of pemetrexed according to NSCLC histology: a review of two Phase III studies.
G. Scagliotti (2009)
10.1002/ijc.20083
Neovascular targeting chemotherapy: Encapsulation of paclitaxel in cationic liposomes impairs functional tumor microvasculature
S. Strieth (2004)
10.4161/cbt.5.1.2346
Paclitaxel encapsulated in cationic lipid complexes (MBT-0206) impairs functional tumor vascular properties as detected by dynamic contrast enhanced magnetic resonance imaging
M. Eichhorn (2006)
10.1097/01.JTO.0000263715.84567.5f
Phase II Trial of Pralatrexate (10-Propargyl-10-deazaaminopterin, PDX) in Patients with Unresectable Malignant Pleural Mesothelioma
L. Krug (2007)
10.1158/1078-0432.CCR-06-1754
A Phase 1 Study of Pralatrexate in Combination with Paclitaxel or Docetaxel in Patients with Advanced Solid Tumors
C. Azzoli (2007)
10.1038/sj.bjc.6606063
Single agent and combination studies of pralatrexate and molecular correlates of sensitivity
M. Serova (2011)
10.1007/s10549-006-9492-5
Topoisomerase II alpha amplification may predict benefit from adjuvant anthracyclines in HER2 positive early breast cancer
E. Arriola (2006)
10.1517/17425250902800153
Ethnic differences in drug metabolism and toxicity from chemotherapy.
V. Phan (2009)
A randomized phase III trial demonstrating that amrubicin could serve as a new standard therapy in second-line therapy of SCLC
First phase 1 trial of NKTR - 102 ( Peg - Irinotecan ) reveals early evidence of broad antitumor activity in three different schedules
A Awada
10.1200/JCO.2011.29.15_SUPPL.7554
Results of a randomized phase IIb study estimating overall survival of pralatrexate versus erlotinib in platinum-pretreated NSCLC.
Jyoti D Patel (2011)
This is a study showing the activity of NKTR-102 in relapsing ovarian cancer
10.1200/JCO.2008.18.1974
Randomized phase II trial comparing amrubicin with topotecan in patients with previously treated small-cell lung cancer: North Japan Lung Cancer Study Group Trial 0402.
A. Inoue (2008)
10.1056/NEJMOA052306
Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.
M. Piccart-Gebhart (2005)
10.1007/BF00255904
New folate analogs of the 10-deaza-aminopterin series
F.M. Sirotnak (2004)
10.1200/JCO.2011.29.15_SUPPL.1034
Antitumor activity in a randomized phase II study comparing two schedules of NKTR-102 in patients (Pts) with pretreated metastatic breast cancer (MBC).
A. Awada (2011)
10.1124/MOL.104.009373
Cellular and Pharmacogenetics Foundation of Synergistic Interaction of Pemetrexed and Gemcitabine in Human Non–Small-Cell Lung Cancer Cells
E. Giovannetti (2005)
10.1016/j.lungcan.2011.01.024
Thymidylate synthase and dihydrofolate reductase expression in non-small cell lung carcinoma: the association with treatment efficacy of pemetrexed.
C. Chen (2011)
10.1056/NEJMOA011795
CHOP Chemotherapy plus Rituximab Compared with CHOP Alone in Elderly Patients with Diffuse Large-B-Cell Lymphoma
B. E. C. Oiffier (2002)
Vascular targeting by Endo- TAG-1 enhances therapeutic efficacy of conventional chemotherapy in lung and pancreatic cancer
ME Eichhorn (2010)
10.1056/NEJMoa0804385
K-ras mutations and benefit from cetuximab in advanced colorectal cancer.
C. Karapetis (2008)



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