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International Journal of Clinical Oncology

, Volume 24, Issue 10, pp 1284–1291 | Cite as

A phase II randomized controlled study of pegylated liposomal doxorubicin and carboplatin vs. gemcitabine and carboplatin for platinum-sensitive recurrent ovarian cancer (GOTIC003/intergroup study)

  • Hiroyuki FujiwaraEmail author
  • Kimio Ushijima
  • Shoji Nagao
  • Yuji Takei
  • Muneaki Shimada
  • Masashi Takano
  • Kiyoshi Yoshino
  • Yoshiaki Kawano
  • Yasuyuki Hirashima
  • Satoru Nagase
  • Shin Nishio
  • Tadaaki Nishikawa
  • Kimihiko Ito
  • Tadahiro Shoji
  • Eizo Kimura
  • Tadao Takano
  • Toru Sugiyama
  • Junzo Kigawa
  • Keiichi Fujiwara
  • Mitsuaki Suzuki
Original Article
  • 184 Downloads

Abstract

Purpose

To compare the efficacy, safety, and tolerability profiles of pegylated liposomal doxorubicin and carboplatin (PLDC) with those of gemcitabine and carboplatin (GC) for the treatment of patients with platinum-sensitive recurrent ovarian cancer.

Methods

Ovarian cancer patients with recurrence > 6 months after first-line platinum and taxane-based therapies were randomly assigned to PLDC [pegylated liposomal doxorubicin 30 mg/m2 plus carboplatin area under the curve (AUC) 5 mg/mL/min on day 1] every 4 weeks or GC (gemcitabine 1000 mg/m2 on days 1 and 8 plus carboplatin AUC 4 mg/mL/min on day 1) every 3 weeks for at least 6 cycles. The primary endpoint was progression-free survival, and overall response rate, overall survival, toxicity, and dose administration were secondary endpoints.

Results

One-hundred patients (49 PLDC; 51 GC) were randomly assigned. Over a median follow-up of 24 months, the median progression-free survival was 12.0 months (95% CI 9.2–15.0) for PLDC and 9.8 months (8.9–12.3) for GC [HR 0.69 (0.455–1.047)] with a difference of 2.2 months. The response rate was 57.1% (41.0–72.3) for PLDC and 56.4% (39.6–72.2) for GC. No obvious differences in toxicity (G3/4) were noted between arms. The median relative dose intensity of planned dose per week was 88.9% for pegylated liposomal doxorubicin and 53.1% for gemcitabine (p < 0.0001).

Conclusions

PLDC and GC are both good treatment candidates for platinum-sensitive recurrent ovarian cancer patients; however, the dose intensity was lower for GC than for PLDC. PLDC had a more favorable risk–benefit profile than that of GC for patients.

Keywords

Platinum-sensitive recurrent ovarian cancer Pegylated liposomal doxorubicin Gemcitabine Randomized clinical trial 

Notes

Acknowledgements

We thank Izumi Kohara, Yoshie Ueki and staff of Global Clinical Research Coordinating Center of Kitasato University Hospital for general support of this trial, and Toshiharu Yamashita and Takaaki Takenaga for statistical support. We also gratefully acknowledge the participation of 100 women in this trial. This study was presented in part at the 20th Biennial meeting of the European Society of Gynaecological Oncology (ESGO2017), November 4–7, 2017, Vienna, Austria and the 17th biennial meeting of the international gynecologic cancer society (IGCS2018), September 14–16, 2018, Kyoto, Japan.

Funding

This study was supported by Janssen Pharmaceutical K.K. and the Japan Society of Clinical Oncology Clinical Research Program Grant. The study was performed and analyzed independently by the study groups (GOTIC and Intergroup in Japan).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Medical institutions

Jichi Medical University, Kurume University School of Medicine, Saitama Medical University International Medical Center, Tottori University School of Medicine, National Defense Medical College Hospital, Osaka University Graduate School of Medicine, Kyushu University, Shizuoka Cancer Center Hospital, Yamagata University School of Medicine, Kansai Rosai Hospital, Iwate Medical University, Kosei Hospital, The Jikei University School of Medicine, Kashiwa Hospital, Hirosaki University School of Medicine & Hospital, Nara Medical University Hospital, Niigata University Medical and Dental Hospital, Mie University Hospital, Ehime University Hospital, Hyogo Medical College Hospital, Miyoshi Central Hospital, Nagaoka Red Cross Hospital, NHO Shikoku Cancer Center, Niigata Cancer Center Hospital, Tottori Municipal Hospital.

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Copyright information

© Japan Society of Clinical Oncology 2019

Authors and Affiliations

  • Hiroyuki Fujiwara
    • 1
    Email author
  • Kimio Ushijima
    • 2
  • Shoji Nagao
    • 3
    • 14
  • Yuji Takei
    • 1
  • Muneaki Shimada
    • 4
    • 13
  • Masashi Takano
    • 5
  • Kiyoshi Yoshino
    • 6
    • 15
  • Yoshiaki Kawano
    • 7
  • Yasuyuki Hirashima
    • 8
  • Satoru Nagase
    • 9
  • Shin Nishio
    • 2
  • Tadaaki Nishikawa
    • 3
  • Kimihiko Ito
    • 10
  • Tadahiro Shoji
    • 11
  • Eizo Kimura
    • 12
  • Tadao Takano
    • 13
  • Toru Sugiyama
    • 11
  • Junzo Kigawa
    • 4
    • 16
  • Keiichi Fujiwara
    • 3
  • Mitsuaki Suzuki
    • 1
    • 17
  1. 1.Department of Obstetrics and GynecologyJichi Medical UniversityShimotsukeJapan
  2. 2.Department of Obstetrics and GynecologyKurume University School of MedicineFukuokaJapan
  3. 3.Department of Gynecologic OncologySaitama Medical University International Medical CenterSaitamaJapan
  4. 4.Department of Obstetrics and GynecologyTottori University School of MedicineTottoriJapan
  5. 5.Department of Obstetrics and GynecologyNational Defense Medical College HospitalSaitamaJapan
  6. 6.Department of Obstetrics and GynecologyOsaka University Graduate School of MedicineOsakaJapan
  7. 7.Department of Obstetrics and Gynecology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  8. 8.Department of GynecologyShizuoka Cancer Center HospitalShizuokaJapan
  9. 9.Department of Obstetrics and GynecologyYamagata University School of MedicineYamagataJapan
  10. 10.Department of Obstetrics and GynecologyKansai Rosai HospitalHyogoJapan
  11. 11.Department of Obstetrics and GynecologyIwate Medical UniversityIwateJapan
  12. 12.Department of Obstetrics and GynecologyKosei HospitalTokyoJapan
  13. 13.Department of Obstetrics and GynecologyTohoku University School of MedicineMiyagiJapan
  14. 14.Department of Gynecologic OncologyHyogo Cancer CenterAkashiJapan
  15. 15.Department of Obstetrics and GynecologyUniversity of Occupational and Environmental HealthKitakyushuJapan
  16. 16.Department of Obstetrics and GynecologyMatsue City HospitalMatsueJapan
  17. 17.Department of Obstetrics and GynecologyShin Yurigaoka General HospitalKawasakiJapan

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