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Does Severe Anemia Caused by Dose-Dense Paclitaxel-Carboplatin Combination Therapy Have an Effect on the Survival of Patients With Epithelial Ovarian Cancer? Retrospective Analysis of the Japanese Gynecologic Oncology Group 3016 Trial
  1. Seisuke Kumagai, MD*,
  2. Toru Sugiyama, MD*,
  3. Tadahiro Shoji, MD*,
  4. Hirofumi Michimae, PhD,
  5. Noriyuki Katsumata, MD,
  6. Daisuke Aoki, MD§,
  7. Fumitoshi Terauchi, MD,
  8. Toshiko Jobo, MD,
  9. Kazunori Ochiai, MD# and
  10. Makoto Yasuda, MD#
  1. * Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine, Iwate;
  2. Department of Clinical Medicine (Biostatistics), Kitasato University School of Pharmacy;
  3. Department of Medical Oncology, National Cancer Center Hospital;
  4. § Department of Obstetrics and Gynecology, School of Medicine, Keio University;
  5. Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo;
  6. Department of Obstetrics and Gynecology, Social Insurance Sagamino Hospital, Kanagawa; and
  7. # Department of Obstetrics and Gynecology, Jikei University School of Medicine, Tokyo, Japan.
  1. Address correspondence and reprint requests to Toru Sugiyama, MD, Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka-city, Iwate 020-8505, Japan. E-mail: sugiyama{at}


Introduction To evaluate the incidence of anemia in patients with epithelial ovarian cancer receiving paclitaxel-carboplatin combination therapy (TC) using data from the Japanese Gynecologic Oncology Group (JGOG) 3016 trial, and to examine the effect of severe anemia on survival during dose-dense TC.

Methods Retrospective analysis was conducted in patients enrolled in the JGOG 3016 trial who underwent at least one cycle of the protocol therapy (n = 622). Hemoglobin values at enrollment and during each cycle of TC were collected. One-to-one matching was performed between patients with and patients without grade 3/4 anemia during TC (anemia and nonanemia groups) to adjust the baseline characteristics of the patients. The cumulative survival curve and median progression-free survival were estimated using the Kaplan-Meier method.

Results Grades 2 to 4 anemia was observed in 19.8% of patients before first-line TC. The incidence of grade 3/4 anemia rapidly increased to 56.1% after the fourth cycle of dose-dense TC. After matching, the median progression-free survival in the anemia (hemoglobin <8.0 g/dL) and nonanemia (hemoglobin >8.0 g/dL) groups was 777 and 1100 days, respectively (P = 0.3493) for patients receiving dose-dense TC. The median progression-free survival in patients receiving conventional TC was similar between the 2 groups.

Conclusions The difference in progression-free survival between patients with epithelial ovarian cancer with and those without severe anemia during TC was not statistically significant, but for patients receiving dose-dense TC, severe anemia seems to have prognostic relevance. Prospective trials are needed to investigate whether the optimal management of chemotherapy-induced anemia, including appropriate use of erythropoiesis-stimulating agents, would further improve the survival of patients with ovarian cancer receiving dose-dense TC.

  • Anemia
  • Chemotherapy
  • Hemoglobin
  • Ovarian cancer
  • Survival

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  • The authors declare that no potential conflict of interest exists.