Far Eastern Memorial Hospital
Conditions: Advanced Ovarian Cancer
Sponsor: Far Eastern Memorial Hospital

Project Summary 
 
 
The combination of paclitaxel and carboplatin is the standard first-line 
chemotherapy for ovarian, fallopian tube and primary peritoneal cancer, and is 
conventionally given via intravenous route every three weeks. Several trials have 
demonstrated a clinically significant survival advantage associated with 
intraperitoneal (IP) chemotherapy compared to intravenous chemotherapy and the 
best outcomes are consistently seen for women who have no residual disease. The 
Japanese Gynecologic Oncology Group (JGOG) challenged the community standard 
of 21-day intravenous regimen by demonstrating the superiority of dose-dense weekly 
paclitaxel in improving the survival of women with stage II-IV cancer.  
 
This retrospective study aimed at comparing the clinical outcomes of women 
with advanced ovarian, fallopian tube or primary peritoneal cancer treated with 
frontline IP versus dose-dense chemotherapy, without addition of bevacizumab. It was 
performed at the Department of Obstetrics and Gynecology of Far Eastern Memorial 
Hospital from March 2006 to June 2019. The medical records of all consecutive 
women aged 20 and above, with advanced ovarian, fallopian tube or primary 
peritoneal cancer [The International Federation of Gynecology and Obstetrics (FIGO) 
stage II-IV] who received postoperative frontline chemotherapy or neoadjuvant 
chemotherapy with platinum/paclitaxel were reviewed. Women who received at least 
one cycle of IP chemotherapy were allocated to the IP group; otherwise, the 
dose-dense group.  
It was anticipated that the IP group would confer a better survival benefit than 
the dose-dense group.  

General Information 
 
Protocol title:  
Comparisons of Clinical Outcomes in Women with Advanced Ovarian Cancer Treated 
with Frontline Intraperitoneal versus Dose-dense Platinum/Paclitaxel Chemotherapy 
 
Clinical Trial Registration Number and date of registration:  
 NCT04135521, 22/10/2019 
 
Number of IRB and date of approval:  
108137-E, 14/10/2019 
 
Name and address of the sponsor/funder: 
Far Eastern Memorial Hospital 
No. 21, Sec. 2, Nanya S. Rd., Banqiao Dist., New Taipei City, Taiwan  
 
Name and title of the investigator: 
Principal investigator: Sheng-Mou Hsiao, MD 
Co-investigator: Wan-Hua Ting, MD 
 
Address and telephone number of the research site:  
Department of Obstetrics and Gynecology, Far Eastern Memorial Hospital,  
No. 21, Sec. 2, Nanya S. Rd., Banqiao Dist., New Taipei City, Taiwan  
Tel.: 886-2-8966-7000, ext. 1424  
Fax: 886-2-8966-5567  

Study Goals and Objectives 
This study aims at comparing the clinical outcomes of women with advanced 
ovarian, fallopian tube or primary peritoneal cancer treated with frontline IP versus 
dose-dense chemotherapy, without addition of bevacizumab. The secondary 
objective of this study is to identify the predictors of progression free survival 
(PFS) and overall survival (OS).  
 
Study Design 
This is a retrospective cohort study conducted between March 2006 and June 
2019. No written informed consent is needed due to its retrospective nature.   
Inclusion criteria: 
Women aged ≧20 years old with stage II-IV ovarian, fallopian tube or primary 
peritoneal cancer who EITHER 
1) received debulking surgery, followed by postoperative IP or dose-dense 
platinum/paclitaxel chemotherapy and were consecutively followed up till disease 
progression or death; OR  
2) received neoadjuvant IP or dose-dense platinum/paclitaxel chemotherapy, 
followed by debulking surgery and postoperative IP or dose-dense 
platinum/paclitaxel chemotherapy and were consecutively followed up till disease 
progression or death 
Exclusion criteria: 
Women without a complete treatment course or discontinued treatment due to 
reasons other than disease progression or death 
 
Methodology 
Group allocation: 
Women who received at least one cycle of IP chemotherapy were allocated to the IP 
group; otherwise, they were allocated to the dose-dense group. 
 
Surgical Method 
 
Debulking surgery including total abdominal hysterectomy, bilateral 
salpingo-oophorectomy, bilateral pelvic and para-aortic lymphadenectomy, 
omentectomy, appendectomy (for mucinous adenocarcinoma or appendiceal 
involvement), excision of peritoneal implants, ascites cytology 
 
Optimal debulking surgery: defined as having residual tumor with a maximal 
diameter less than 1 cm after cytoreductive surgery 
 
Drug Administration Schedule: 

 
Intraperitoneal group: 135 mg/m2 intravenous paclitaxel over a 3 or 24 hours 
period on day 1, followed by 75-100 mg/m2 IP cisplatin on day 2 and 60 
mg/m2 IP paclitaxel on day 8 
 
Dose-dense group: intravenous carboplatin at AUC of 6 mg/mL per min on 
day 1, followed by 80 mg/m2 intravenous paclitaxel on days 1, 8, and 15 
 
Rules for Dose Modification: 
 
For women with significantly impaired renal function (i.e., estimated 
glomerular filtration rate<50 mL/min/1.73 m2), carboplatin AUC=6 was used 
instead of cisplatin. 
 
The carboplatin or cisplatin dose was reduced when febrile neutropenia 
occurred, an absolute neutrophil count less than 0.5 x 109 cells per L persisted 
for 7 days or more, the platelet count was less than 10 x 109 per L, the platelet 
count was between 10 x 109 per L and 50 x 109 per L with bleeding 
tendencies, or the treatment was delayed for haematological toxicity for more 
than 1 week.  
 
The dose of paclitaxel was reduced in patients who had grade 2 or higher 
peripheral neuropathy. 
 
Measurements: 
1) Response criteria: 
 
Complete response  the disappearance of all evidence (including CA-125 and 
image) of tumor for at least 4 weeks, it could not be determined by CA-125 alone 
 
Partial response  a ≥50% reduction in the products of each measurable lesion 
or a ≥50% reduction of CA-125 for at least 4 weeks 
 
Progressive disease  a ≥25% increase in the size of one or more measurable   
lesions, the appearance of new lesions, or a ≥25% increase of CA-125 
 
Stable disease  any condition not meeting any of the above criteria 
2) Definitions of survival and methods of measurement 
 
Overall survival  the time interval from the date of surgery to the date of 
death from any cause or the last follow-up 
 
Progression free survival  the time interval from the date of surgery to 
clinically defined recurrence, disease progression, or the last follow-up 
 
Reasons for early cessation of trial therapy: 
Disease progression, death or grade 3-4 chemotherapy related adverse events  
 
 

Data Management and Statistical Analysis 
All the data collected will be kept confidential and anonymous, and the results 
reported in the aggregate. Information on individuals is only used by the principal 
and co-investigators for the purpose of the study, it will not be shared with the 
third party, except when applicable by law. Each individual will be designated a 
research number as the substitute for her name.  
 
The research results will be analyzed and published in scientific journal using  
Stata version 11.0 (Stata Corp, College Station, TX). Survival curves are generated 
using the Kaplan–Meier method, and differences in the survival curves were 
calculated with the log-rank test. A p-value less than 0.05 is considered statistically 
significant. A Cox proportional hazards model was used to identify predictors of PFS 
and OS.  
 
Dissemination of Results and Publication Policy 
The results of the study will be written into a manuscript and submitted for 
publication in English international journal by both the principal and 
co-investigators.  
 
Ethics 
This study has been approved by the Research Ethics Committee of Far Eastern 
Memorial Hospital.  
Other support for the Project: Not applicable 
Collaboration with other scientists or research institutions: Not applicable 
Links to other projects: Not applicable  
Financing and Insurance: Not applicable