PMID- 31179244
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 9
DP  - 2019
TI  - A Dose Escalation Study of Trientine Plus Carboplatin and Pegylated Liposomal 
      Doxorubicin in Women With a First Relapse of Epithelial Ovarian, Tubal, and 
      Peritoneal Cancer Within 12 Months After Platinum-Based Chemotherapy.
PG  - 437
LID - 10.3389/fonc.2019.00437 [doi]
LID - 437
AB  - Background: Epithelial ovarian cancer (EOC) is the leading cause of gynecological 
      cancer-related deaths worldwide. Preclinical studies found that copper-lowering 
      agents could re-sensitize platinum-resistant cancer cells by enhancing the human 
      copper transporter 1 (hCtr1)-mediated uptake of platinum. In the clinic, 
      re-sensitization of platinum-resistance in relapsed EOC has been discovered by 
      the application of trientine plus platinum (NCT01178112). However, no 
      pharmacokinetic data of trientine has been reported in cancer patients. Purpose: 
      Our study aimed to explore the safety and activity of trientine combined with 
      carboplatin and pegylated liposomal doxorubicin (PLD) in patients with EOC, 
      tubal, and peritoneal cancer who experienced disease progression during 
      platinum-based chemotherapy or showed relapse <12 months after completing 
      first-line chemotherapy. Also, we aimed to demonstrate pharmacokinetic parameters 
      and to discover potential biomarkers in our EOC patients. Methods: In this dose 
      escalation study, 18 Asian patients in six dosing cohorts received fixed doses of 
      carboplatin (AUC 4) and PLD (LipoDox(R), TTY Biopharm Co. Ltd., Taipei, Taiwan) (40 
      mg/m(2), day 1 per 4-week cycle), and escalated daily trientine doses (range: 
      300-1800 mg; initiated 7 days before the 1st combination cycle) according to a 3 
      + 3 design. Results: No dose-limiting toxicity or treatment-related death was 
      observed. Four patients (22.2%) developed grade 3 drug-related adverse events 
      (AEs), whereas no grade 4 AEs were encountered. Anemia and grade 2 dizziness were 
      the most common hematological toxicity and neurotoxicity, respectively. In a 
      pharmacokinetics comparison with healthy volunteers in the literature, our 
      patients achieved greater absorption after oral trientinem, and more rapid 
      elimination of triethylenetetramine dihydrochloride at high doses. The clinical 
      benefit rate was 33.3 and 50.0% in the platinum-resistant and the partially 
      platinum-sensitive group, respectively. A high baseline serum iron level and low 
      serum copper level might help differentiate subgroups of patients with different 
      clinical responses. Nevertheless, no associations of the clinical response with 
      the levels of serum hCtr1, ceruloplasmin, or copper were observed. Conclusion: 
      Combination therapy with carboplatin, trientine, and PLD was well-tolerated and 
      safe. Our results encourage the development of a future phase II trial. Clinical 
      trial registration: ClinicalTrials.gov # NCT03480750.
FAU - Huang, Yu-Fang
AU  - Huang YF
AD  - Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, 
      College of Medicine, National Cheng Kung University, Tainan, Taiwan.
FAU - Kuo, Macus Tien
AU  - Kuo MT
AD  - Department of Molecular Pathology, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, United States.
FAU - Liu, Yi-Sheng
AU  - Liu YS
AD  - Department of Medical Imaging, College of Medicine, National Cheng Kung 
      University Hospital, National Cheng Kung University, Tainan, Taiwan.
FAU - Cheng, Ya-Min
AU  - Cheng YM
AD  - Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, 
      College of Medicine, National Cheng Kung University, Tainan, Taiwan.
FAU - Wu, Pei-Ying
AU  - Wu PY
AD  - Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, 
      College of Medicine, National Cheng Kung University, Tainan, Taiwan.
FAU - Chou, Cheng-Yang
AU  - Chou CY
AD  - Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, 
      College of Medicine, National Cheng Kung University, Tainan, Taiwan.
LA  - eng
SI  - ClinicalTrials.gov/NCT03480750
PT  - Case Reports
DEP - 20190524
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC6544081
OTO - NOTNLM
OT  - adverse effect
OT  - carboplatin
OT  - ceruloplasmin
OT  - copper
OT  - human copper transporter 1
OT  - ovarian cancer
OT  - pegylated liposomal doxorubicin
OT  - trientine
EDAT- 2019/06/11 06:00
MHDA- 2019/06/11 06:01
PMCR- 2019/01/01
CRDT- 2019/06/11 06:00
PHST- 2019/03/20 00:00 [received]
PHST- 2019/05/07 00:00 [accepted]
PHST- 2019/06/11 06:00 [entrez]
PHST- 2019/06/11 06:00 [pubmed]
PHST- 2019/06/11 06:01 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2019.00437 [doi]
PST - epublish
SO  - Front Oncol. 2019 May 24;9:437. doi: 10.3389/fonc.2019.00437. eCollection 2019.