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European Journal of Gynaecological Oncology  2020, Vol. 41 Issue (3): 380-385    DOI: 10.31083/j.ejgo.2020.03.5156
Original Research Previous articles | Next articles
Relationship between usefulness of irinotecan and pegylated liposomal doxorubicin therapy and the UGT1A1 genotype in patients with recurrent ovarian cancer (TGCU 104 study)
T. Shoji1(), E. Takatori1, M. Kagabu1, M. Futagami2, Y. Yokoyama2, H. Tokunaga3, N. Yaegashi3, T. Ohta4, T. Watanabe5, T Sugiyama
1Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka 020-8505, Japan
2Department of Obstetrics and Gynecology, Hirosaki University School of Medicine, Hirosaki, Japan
3Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan
4Department of Obstetrics and Gynecology, Yamagata University Faculty of Medicine, Yamagata, Japan
5Department of Obstetrics and Gynecology, Fukushima Medical University School of Medicine, Fukushima, Japan
6Department of Obstetrics and Gynecology, Takagi Hospital, Okawa, Japan
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Abstract  

Objective: The authors investigated the relationship between the usefulness of CPT-11 + PLD combination therapy and the UGT1A1 genotype. Materials and Methods: Forty-one patients who provided informed consent were divided into the following two groups according to UGT1A1 genotypes: wild type and non-wild type. Adverse events, antitumor effect, and outcomes were compared between these two groups. Results: Twenty-three patients were wild type and 18 were non-wild type for UGT1A1. A total of 94 and 73 treatment cycles were prescribed to the wild-type and non-wild-type groups, respectively. No significant differences in the incidence of any grade 3 or higher adverse events were observed between the two groups. However, the next treatment cycle was postponed in 9.6% of the wildtype group and 12.3% of the non-wild-type group (p = 0.891). The antitumor effects as assessed by response rate were 26.1% in the wildtype group and 55.6% in the non-wild-type group (p = 0.054). The median observation period was 13 months. The median progression-free survival was three months in the wild-type group vs. five months in non-wild-type group (p = 0.913), while the median overall survival was 24 vs. 22 months (p = 0.535). Conclusions: This study did not demonstrate a statistically significant difference in the usefulness of CPT-11 + PLD combination therapy for recurrent ovarian cancer between the two groups of UGT1A1 genotypes. This study was considered to have significance as the first study conducted in Japan to prospectively evaluate the relationship between the usefulness of CPT-11-based chemotherapy and the UGT1A1 genotype for recurrent ovarian cancer.

Key words:  Recurrent ovarian cancer      Chemotherapy      CPT-11      PLD      UGT1A1     
Submitted:  06 February 2019      Accepted:  16 July 2019      Published:  15 June 2020     
*Corresponding Author(s):  T. Shoji     E-mail:  tshoji@iwate-med.ac.jp

Cite this article: 

T. Shoji, E. Takatori, M. Kagabu, M. Futagami, Y. Yokoyama, H. Tokunaga, N. Yaegashi, T. Ohta, T. Watanabe, T Sugiyama. Relationship between usefulness of irinotecan and pegylated liposomal doxorubicin therapy and the UGT1A1 genotype in patients with recurrent ovarian cancer (TGCU 104 study). European Journal of Gynaecological Oncology, 2020, 41(3): 380-385.

URL: 

https://ejgo.imrpress.com/EN/10.31083/j.ejgo.2020.03.5156     OR     https://ejgo.imrpress.com/EN/Y2020/V41/I3/380

Table 1  - Patients Characteristics
Wild type (n = 23) Non-Wild type (n = 18) p value
Age (median,range) 57 (38-74) 55 (41-70) 0.519**
PS 0.338*
0 20 14
1 3 4
Cell type 0.815*
Serous 18 14
Mucinus 1 0
Clear 4 3
Endometrioid 0 1
Prior regimens (median) 0.252*
1 7 10
2 8 6
3 < 3 7
TFI 0.355*
3 <, < 6 9 10
3 > 14 8
Cycle number (median,range) 2 (1-16) 3.5 (2-9) 0.957**
Recurrent sites 0.730*
Pelvic cavity 2 2
Peritoneum 13 9
Lymph nodes 8 8
Liver 2 0
Spleen 1 0
Lung 2 1
Table 2  - Adverse effects (n = 41,> Grade3)
Wild type
(n = 23)
Non-Wild type
(n = 18)
p value
Leucopenia 0.353 0.261 0.5299
Neutropenia 0.529 0.522 0.9617
Anemia 0.118 0.043 0.3786
Thrombocytopenia 0.059 0.043 0.8258
Mucositis 0 0 -
Hand foot 0 0 -
Diarrhea 0 0.118 0.0915
Nausea 0.059 0 0.2388
Vomiting 0.118 0.043 0.3786
Appetite loss 0 0 -
Fatigue 0 0.043 0.3839
Table 3  - Tumor Response (n = 41)
Wild type Non-Wild type Total p value
CR 0 0 0
PR 6 10 16
SD 7 5 12
PD 10 3 13
Overall response (%) 6 (26.1%) 10 (55.6%) 16 (39.0%) 0.054
CR/PR+SD (%) 13 (56.5%) 15 (83.3%) 28 (68.3%) 0.067
Figure 1.  — Progression-free survival. Progression-free survival. The median PFS was 3 months (range, 2-45 months) for the wild-type group, and 5 months (2-94 months) for the non-wild-type group. There was no statistically significant difference (hazard ratios [HR]: 0.99, 95% confidence interval [CI]: 0.52-1.95, p = 0.913) between the wild-type and non-wild-type groups.

Figure 2.  — Overall survial. Overall survival. The median OS was 24 months (range, 2-64 months), for the wild-type group, and 22 months (range 2-94 months) for the non-wild-type group. There was no statistically significant difference (HR: 1.15, 95% CI: 0.45-3.14, p = 0.535) between the wild-type and non-wild-type groups.

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