1Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
2Department of Obstetrics and Gynecology, GangNeung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea
Copyright © 2023 by the Korean Cancer Association
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ethical Statement
The study protocol was approved by the institutional review board of Asan Medical Center (approval date: November 26, 2015; approval #2015-1296) and adhered to the principles in the Declaration of Helsinki. All participants provided written informed consent. The study was performed in compliance with the Declaration of Helsinki and was registered in ClinicalTrials.gov (NCT02739529).
Author Contributions
Conceived and designed the analysis: Nam SH, Kim YM, Lee SW, Lee YJ.
Collected the data: Nam SH, Kim YM, Lee SW, Lee YJ.
Contributed data or analysis tools: Nam SH, Kim YM, Lee SW.
Performed the analysis: Nam SH, Kim YM, Lee SW.
Wrote the paper: Nam SH, Kim YM, Lee SW, Lee YJ.
Conflicts of Interest
This study was sponsored by Samyang, and Genexol-PM was provided by Samyang. The authors declare no competing interests in relation to this article.
Serious adverse events |
Genexol PM 100 mg/m2+ Carboplatin 5 AUC |
Genexol PM 120 mg/m2+ Carboplatin 5 AUC |
Genexol PM 120 mg/m2+ Carboplatin 6 AUC |
|||
---|---|---|---|---|---|---|
No. of patients | No. of casesa) | No. of patients | No. of casesa) | No. of patients | No. of casesa) | |
Hematologic disorders | ||||||
Neutropenia | 1 | 1 | 1 | 2 | 0 | 0 |
Infections | ||||||
Pneumonia | 0 | 0 | 1 | 1 | 0 | 0 |
Total | 1 | 1 | 1 | 3 | 0 | 0 |
Characteristics of the study patients
Characteristic | No. (n=18) |
---|---|
Screened | 18 |
Eligible | 18 |
Assessable for toxicity | 18 |
Assessable for response | 17 |
Intention-to-treat group | 18 |
Per protocol group | 13 |
Age (yr), median (range) | 56 (36–68) |
ECOG performance status | |
0 | 18 |
1 | 0 |
Origin of the tumor | |
Ovary | 13 |
Fallopian tube | 2 |
Endometrium | 3 |
Histopathological grade | |
G1: well-differentiated | 1 |
G2: moderately differentiated | 3 |
G3: poorly differentiated | 13 |
Unknown | 1 |
Recurrent disease | 7 |
Previous lines of systemic therapies | |
0 | 12 |
1 | 6 |
FIGO stage at diagnosis | |
IA | 1 |
IC | 1 |
IIA | 1 |
IIB | 2 |
IIIA | 1 |
IIIB | 4 |
IIIC | 7 |
IVB | 1 |
ECOG, Eastern Cooperative Oncology Group; FIGO, The International Federation of Gynecology and Obstetrics.
Dosage escalation scheme and administration of treatments
Study stage | Genexol PM dose (mg/m2) | Carboplatin dose (AUC) | No. of patients | Patients that completed treatment | Total No. of cycles | No. of patients with DLT |
---|---|---|---|---|---|---|
1 | 100 | 5 | 6 | 5 | 31 | 0 |
2 | 120 | 5 | 6 | 5 | 33 | 0 |
3 | 120 | 6 | 6 | 3 | 28 | 0 |
AUC, area under the curve; DLT, dose-limiting toxicity.
Adverse drug reactions per patient stratified by dose level
Adverse drug reactions | Genexol PM 100 mg/m2+ Carboplatin 5 AUC (n=6) |
Genexol PM 120 mg/m2+ Carboplatin 5 AUC (n=6) |
Genexol PM 120 mg/m2+ Carboplatin 6 AUC (n=6) | |||
---|---|---|---|---|---|---|
Grade 1–4 | ≥Grade 3 | Grade 1–4 | ≥Grade 3 | Grade 1–4 | ≥Grade 3 | |
Hematologic | ||||||
Neutropenia | 6 (100) | 6 (100) | 6 (100) | 6 (100) | 6 (100) | 6 (100) |
Anemia | 5 (83.3) | 3 (50.0) | 2 (33.3) | 1 (16.7) | 3 (50.0) | 2 (33.3) |
Thrombocytopenia | 2 (33.3) | 1 (16.7) | 0 | 0 | 3 (50.0) | 0 |
Non-hematologic | ||||||
Anorexia | 1 (16.7) | 0 | 2 (33.3) | 0 | 1 (16.7) | 0 |
Constipation | 3 (50.0) | 0 | 3 (50.0) | 0 | 1 (16.7) | 0 |
Dyspepsia | 1 (16.7) | 0 | 1 (16.7) | 0 | 2 (33.3) | 0 |
Nausea | 1 (16.7) | 0 | 4 (66.7) | 0 | 1 (16.7) | 0 |
Vomiting | 0 | 0 | 3 (50.0) | 0 | 1 (16.7) | 0 |
Fever | 1 (16.7) | 0 | 2 (33.3) | 0 | 1 (16.7) | 0 |
Pain | 1 (16.7) | 0 | 3 (50.0) | 0 | 2 (33.3) | 0 |
ALT increase | 2 (33.3) | 0 | 3 (50.0) | 0 | 2 (33.3) | 0 |
AST increase | 2 (33.3) | 0 | 2 (33.3) | 0 | 2 (33.3) | 0 |
Headache | 1 (16.7) | 0 | 0 | 0 | 1 (16.7) | 0 |
Peripheral neuropathy | 2 (33.3) | 0 | 3 (50.0) | 0 | 3 (50.0) | 0 |
Hypersensitivity | 0 | 0 | 1 (16.7) | 1 (16.7) | 2 (33.3) | 0 |
Allergy reaction | 0 | 0 | 2 (33.3) | 0 | 2 (33.3) | 0 |
Pruritus | 2 (33.3) | 0 | 2 (33.3) | 0 | 2 (33.3) | 0 |
Urticaria | 1 (16.7) | 0 | 0 | 0 | 0 | 0 |
Alopecia | 5 (83.3) | 0 | 6 (100) | 0 | 6 (100) | 0 |
Insomnia | 2 (33.3) | 0 | 2 (33.3) | 0 | 2 (33.3) | 0 |
Values are presented as number (%). Some patients had multiple cases of the indicated condition. ALT, alanine aminotransferase; AST, aspartate aminotransferase; AUC, area under the curve.
Serious adverse events
Serious adverse events | Genexol PM 100 mg/m2+ Carboplatin 5 AUC |
Genexol PM 120 mg/m2+ Carboplatin 5 AUC |
Genexol PM 120 mg/m2+ Carboplatin 6 AUC | |||
---|---|---|---|---|---|---|
No. of patients | No. of cases |
No. of patients | No. of cases |
No. of patients | No. of cases | |
Hematologic disorders | ||||||
Neutropenia | 1 | 1 | 1 | 2 | 0 | 0 |
Infections | ||||||
Pneumonia | 0 | 0 | 1 | 1 | 0 | 0 |
Total | 1 | 1 | 1 | 3 | 0 | 0 |
Values are presented as number. AUC, area under the curve.
a)Some patients had multiple cases of the indicated condition.
Treatment response rate stratified by dose level
Group | Total No. of cycles | Investigator evaluation | CA-125 response | Best overall response (reviewer evaluation) |
---|---|---|---|---|
100 mg/m2+5 AUC | C6D15 | CR | Response | CR |
C6D15 | NA | Response | Response | |
C6D15 | CR | No response | CR | |
C6D15 | NA | Response | Response | |
C1D15 | NE | NE | NE | |
C6D15 | CR | Response | CR | |
120 mg/m2+5 AUC | C6D15 | NA | Response | Response |
C6D15 | NA | No response | No response | |
C6D15 | NA | Response | Response | |
C6D15 | NA | Response | Response | |
C6D15 | NA | Response | Response | |
C3D15 | PR | NE | PR | |
120 mg/m2+6 AUC | C2D15 | NA | NE | NA |
C3D15 | PR | Response | PR | |
C5D8 | NA | No response | No response | |
C6D15 | NA | No response | No response | |
C6D15 | NA | Response | Response | |
C6D15 | NA | Response | Response |
AUC, area under the curve; CA-125, carbohydrate antigen 125; CR, complete response; NA, not available; NE, not evaluable; PR, partial response.
ECOG, Eastern Cooperative Oncology Group; FIGO, The International Federation of Gynecology and Obstetrics.
AUC, area under the curve; DLT, dose-limiting toxicity.
Values are presented as number (%). Some patients had multiple cases of the indicated condition. ALT, alanine aminotransferase; AST, aspartate aminotransferase; AUC, area under the curve.
Values are presented as number. AUC, area under the curve. Some patients had multiple cases of the indicated condition.
AUC, area under the curve; CA-125, carbohydrate antigen 125; CR, complete response; NA, not available; NE, not evaluable; PR, partial response.