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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)

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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.

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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).

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, 329-0498, Tochigi, Japan

    Hiroyuki Fujiwara, Yuji Takei & Mitsuaki Suzuki

  2. Department of Obstetrics and Gynecology, Kurume University School of Medicine, Fukuoka, Japan

    Kimio Ushijima & Shin Nishio

  3. Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan

    Shoji Nagao, Tadaaki Nishikawa & Keiichi Fujiwara

  4. Department of Obstetrics and Gynecology, Tottori University School of Medicine, Tottori, Japan

    Muneaki Shimada & Junzo Kigawa

  5. Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Saitama, Japan

    Masashi Takano

  6. Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan

    Kiyoshi Yoshino

  7. Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Yoshiaki Kawano

  8. Department of Gynecology, Shizuoka Cancer Center Hospital, Shizuoka, Japan

    Yasuyuki Hirashima

  9. Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan

    Satoru Nagase

  10. Department of Obstetrics and Gynecology, Kansai Rosai Hospital, Hyogo, Japan

    Kimihiko Ito

  11. Department of Obstetrics and Gynecology, Iwate Medical University, Iwate, Japan

    Tadahiro Shoji & Toru Sugiyama

  12. Department of Obstetrics and Gynecology, Kosei Hospital, Tokyo, Japan

    Eizo Kimura

  13. Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Miyagi, Japan

    Muneaki Shimada & Tadao Takano

  14. Department of Gynecologic Oncology, Hyogo Cancer Center, Akashi, Japan

    Shoji Nagao

  15. Department of Obstetrics and Gynecology, University of Occupational and Environmental Health, Kitakyushu, Japan

    Kiyoshi Yoshino

  16. Department of Obstetrics and Gynecology, Matsue City Hospital, Matsue, Japan

    Junzo Kigawa

  17. Department of Obstetrics and Gynecology, Shin Yurigaoka General Hospital, Kawasaki, Japan

    Mitsuaki Suzuki

Authors
  1. Hiroyuki Fujiwara
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  2. Kimio Ushijima
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  19. Keiichi Fujiwara
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  20. Mitsuaki Suzuki
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Corresponding author

Correspondence to Hiroyuki Fujiwara.

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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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Fujiwara, H., Ushijima, K., Nagao, S. et al. 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). Int J Clin Oncol 24, 1284–1291 (2019). https://doi.org/10.1007/s10147-019-01471-5

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