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Preclinical activity of melflufen (J1) in ovarian cancer

Charlotte Carlier UGent, Sara Strese, Kristina Viktorsson, Ebba Velander, Peter Nygren, Maria Uustalu, Therese Juntti, Rolf Lewensohn, Rolf Larsson, Jack Spira, et al. (2016) ONCOTARGET. 7(37). p.59322-59335
abstract
Ovarian cancer carries a significant mortality. Since symptoms tend to be minimal, the disease is often diagnosed when peritoneal metastases are already present. The standard of care in advanced ovarian cancer consists of platinum-based chemotherapy combined with cytoreductive surgery. Unfortunately, even after optimal cytoreduction and adjuvant chemotherapy, most patients with stage III disease will develop a recurrence. Intraperitoneal administration of chemotherapy is an alternative treatment for patients with localized disease. The pharmacological and physiochemical properties of melflufen, a peptidase potentiated alkylator, raised the hypothesis that this drug could be useful in ovarian cancer and particularily against peritoneal carcinomatosis. In this study the preclinical effects of melflufen were investigated in different ovarian cancer models. Melflufen was active against ovarian cancer cell lines, primary cultures of patient-derived ovarian cancer cells, and inhibited the growth of subcutaneous A2780 ovarian cancer xenografts alone and when combined with gemcitabine or liposomal doxorubicin when administered intravenously. In addition, an intra- and subperitoneal xenograft model showed activity of intraperitoneal administered melflufen for peritoneal carcinomatosis, with minimal side effects and modest systemic exposure. In conclusion, results from this study support further investigations of melflufen for the treatment of peritoneal carcinomatosis from ovarian cancer, both for intravenous and intraperitoneal administration.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
intraperitoneal treatment, preclinical, Ovarian cancer, in vivo, melflufen
journal title
ONCOTARGET
Oncotarget
volume
7
issue
37
pages
59322 - 59335
Web of Science type
Article
Web of Science id
000387153900046
JCR category
ONCOLOGY
JCR impact factor
5.168 (2016)
JCR rank
44/217 (2016)
JCR quartile
1 (2016)
ISSN
1949-2553
DOI
10.18632/oncotarget.11163
language
English
UGent publication?
yes
classification
A1
additional info
the first two authors contributed equally to this work; the last two authors share senior authorship
copyright statement
I have retained and own the full copyright for this publication
id
8047320
handle
http://hdl.handle.net/1854/LU-8047320
date created
2016-08-10 16:45:28
date last changed
2017-07-06 11:57:08
@article{8047320,
  abstract     = {Ovarian cancer carries a significant mortality. Since symptoms tend to be minimal, the disease is often diagnosed when peritoneal metastases are already present. The standard of care in advanced ovarian cancer consists of platinum-based chemotherapy combined with cytoreductive surgery. Unfortunately, even after optimal cytoreduction and adjuvant chemotherapy, most patients with stage III disease will develop a recurrence. Intraperitoneal administration of chemotherapy is an alternative treatment for patients with localized disease. The pharmacological and physiochemical properties of melflufen, a peptidase potentiated alkylator, raised the hypothesis that this drug could be useful in ovarian cancer and particularily against peritoneal carcinomatosis. In this study the preclinical effects of melflufen were investigated in different ovarian cancer models. Melflufen was active against ovarian cancer cell lines, primary cultures of patient-derived ovarian cancer cells, and inhibited the growth of subcutaneous A2780 ovarian cancer xenografts alone and when combined with gemcitabine or liposomal doxorubicin when administered intravenously. In addition, an intra- and subperitoneal xenograft model showed activity of intraperitoneal administered melflufen for peritoneal carcinomatosis, with minimal side effects and modest systemic exposure. In conclusion, results from this study support further investigations of melflufen for the treatment of peritoneal carcinomatosis from ovarian cancer, both for intravenous and intraperitoneal administration.},
  author       = {Carlier, Charlotte and Strese, Sara and Viktorsson, Kristina and Velander, Ebba and Nygren, Peter and Uustalu, Maria and Juntti, Therese and Lewensohn, Rolf and Larsson, Rolf and Spira, Jack and De Vlieghere, Elly and Ceelen, Wim and Gullbo, Joachim},
  issn         = {1949-2553},
  journal      = {ONCOTARGET},
  keyword      = {intraperitoneal treatment,preclinical,Ovarian cancer,in vivo,melflufen},
  language     = {eng},
  number       = {37},
  pages        = {59322--59335},
  title        = {Preclinical activity of melflufen (J1) in ovarian cancer},
  url          = {http://dx.doi.org/10.18632/oncotarget.11163},
  volume       = {7},
  year         = {2016},
}

Chicago
Carlier, Charlotte, Sara Strese, Kristina Viktorsson, Ebba Velander, Peter Nygren, Maria Uustalu, Therese Juntti, et al. 2016. “Preclinical Activity of Melflufen (J1) in Ovarian Cancer.” Oncotarget 7 (37): 59322–59335.
APA
Carlier, C., Strese, S., Viktorsson, K., Velander, E., Nygren, P., Uustalu, M., Juntti, T., et al. (2016). Preclinical activity of melflufen (J1) in ovarian cancer. ONCOTARGET, 7(37), 59322–59335.
Vancouver
1.
Carlier C, Strese S, Viktorsson K, Velander E, Nygren P, Uustalu M, et al. Preclinical activity of melflufen (J1) in ovarian cancer. ONCOTARGET. 2016;7(37):59322–35.
MLA
Carlier, Charlotte, Sara Strese, Kristina Viktorsson, et al. “Preclinical Activity of Melflufen (J1) in Ovarian Cancer.” ONCOTARGET 7.37 (2016): 59322–59335. Print.