PMID- 23863356
OWN - NLM
STAT- MEDLINE
DCOM- 20131227
LR  - 20190221
IS  - 1095-6859 (Electronic)
IS  - 0090-8258 (Linking)
VI  - 131
IP  - 1
DP  - 2013 Oct
TI  - Phase I trial of a formulated IL-12 plasmid in combination with carboplatin and 
      docetaxel chemotherapy in the treatment of platinum-sensitive recurrent ovarian 
      cancer.
PG  - 169-73
LID - S0090-8258(13)00996-7 [pii]
LID - 10.1016/j.ygyno.2013.07.081 [doi]
AB  - OBJECTIVES: The primary objective of this study was to evaluate the safety and 
      tolerability of a formulated IL-12 plasmid administered intraperitoneally (IP) in 
      conjunction with intravenous (IV) carboplatin/docetaxel in platinum-sensitive 
      ovarian cancer patients. METHODS: Escalating doses of IL-12 plasmid (phIL-12) 
      formulated with the lipopolymer PEG-PEI-Cholesterol (PPC) were administered IP 
      every 10-11 days for a total of four treatments and the highest dose was expanded 
      to eight treatments. Patients also received IV carboplatin (AUC 5) and docetaxel 
      (75 mg/m(2)) every 21 days. Patients were followed for safety, biological 
      activity and antitumor activity after phIL-12/PPC treatment. RESULTS: All 13 
      patients enrolled in the study received both phIL-12/PPC and chemotherapy 
      treatment. There were 49 plasmid-associated adverse events (AEs). The most common 
      AEs were abdominal pain, transient hypotension, low grade fever, catheter site 
      pain, chills, dysgeusia, infusion-related reaction, and nausea. These AEs 
      appeared to be plasmid dose related. Grade 3 AEs included manageable abdominal 
      pain and cytokine release syndrome. There were no dose limiting toxicities and 
      the plasmid treatment did not augment the chemotherapy-associated AEs. The best 
      overall antitumor response (17% CR, 33% PR, 42% SD and 8% PD) was typical of the 
      patient population enrolled for the study. Translational studies showed rise in 
      IFN-gamma and TNF-alpha concentrations in a dose dependent manner. CONCLUSIONS: The 
      escalating doses and cycles of intraperitoneal phIL-12/PPC when combined with 
      carboplatin/docetaxel chemotherapy in recurrent ovarian cancer patients were well 
      tolerated and did not appear to exacerbate the side effects or attenuate the 
      efficacy of the chemotherapy treatment.
CI  - (c) 2013. Published by Elsevier Inc. All rights reserved.
FAU - Anwer, Khursheed
AU  - Anwer K
AD  - EGEN, Inc., Huntsville, AL, USA. Electronic address: kanwer@egeninc.com.
FAU - Kelly, F Joseph
AU  - Kelly FJ
FAU - Chu, Christina
AU  - Chu C
FAU - Fewell, Jason G
AU  - Fewell JG
FAU - Lewis, Danny
AU  - Lewis D
FAU - Alvarez, Ronald D
AU  - Alvarez RD
LA  - eng
GR  - 1R01FD003374-01/FD/FDA HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
DEP - 20130714
PL  - United States
TA  - Gynecol Oncol
JT  - Gynecologic oncology
JID - 0365304
RN  - 0 (Taxoids)
RN  - 15H5577CQD (Docetaxel)
RN  - 187348-17-0 (Interleukin-12)
RN  - BG3F62OND5 (Carboplatin)
SB  - IM
EIN - Gynecol Oncol. 2014 Jul;134(1):216
MH  - Abdominal Pain/chemically induced
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*adverse effects/therapeutic use
MH  - Carboplatin/administration & dosage
MH  - Carcinoma, Ovarian Epithelial
MH  - Chills/chemically induced
MH  - Docetaxel
MH  - Dysgeusia/chemically induced
MH  - Female
MH  - Fever/chemically induced
MH  - Genetic Therapy
MH  - Humans
MH  - Hypotension/chemically induced
MH  - Interleukin-12/administration & dosage/*adverse effects/genetics
MH  - Middle Aged
MH  - Nausea/chemically induced
MH  - Neoplasms, Glandular and Epithelial/*drug therapy
MH  - Ovarian Neoplasms/*drug therapy
MH  - Plasmids/administration & dosage
MH  - Taxoids/administration & dosage
OTO - NOTNLM
OT  - Chemotherapy
OT  - Gene therapy
OT  - Interleukin-12
OT  - Ovarian cancer
OT  - Plasmid DNA
EDAT- 2013/07/19 06:00
MHDA- 2013/12/29 06:00
CRDT- 2013/07/19 06:00
PHST- 2013/04/09 00:00 [received]
PHST- 2013/07/01 00:00 [revised]
PHST- 2013/07/07 00:00 [accepted]
PHST- 2013/07/19 06:00 [entrez]
PHST- 2013/07/19 06:00 [pubmed]
PHST- 2013/12/29 06:00 [medline]
AID - S0090-8258(13)00996-7 [pii]
AID - 10.1016/j.ygyno.2013.07.081 [doi]
PST - ppublish
SO  - Gynecol Oncol. 2013 Oct;131(1):169-73. doi: 10.1016/j.ygyno.2013.07.081. Epub 
      2013 Jul 14.