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Epirubicin, Cisplatin, and Capecitabine for Primary Platinum-Resistant or Platinum-Refractory Epithelial Ovarian Cancer: Results of a Retrospective, Single-Institution Study
  1. Karen Sayal, MA, MB BChir*,
  2. Ioannis Gounaris, PhD, MRCP*,,
  3. Bristi Basu, PhD, MRCP*,,
  4. Sue Freeman, FRCR,
  5. Penny Moyle, FRCR,
  6. Karen Hosking, BSc§,
  7. Mahesh Iddawela, PhD, MRCP*,
  8. Mercedes Jimenez-Linan, PhD, FRCPath,
  9. Jean Abraham, PhD, MRCP*,§,
  10. James Brenton, PhD, FRCP*,,
  11. Helen Hatcher, PhD, FRCP*,§,
  12. Helena Earl, PhD, FRCP*,§ and
  13. Christine Parkinson, PhD, MRCP*
  1. *Department of Oncology, Cambridge University NHS Foundation Trust, Cambridge, United Kingdom;
  2. Cancer Research United Kingdom Cambridge Institute, University of Cambirdge, Li Ka Shing Centre, Cambridge, United Kingdom;
  3. Department of Radiology, Cambridge University NHS Foundation Trust, Cambridge, United Kingdom;
  4. §Department of Oncology, University of Cambridge, Cambridge, United Kingdom; and
  5. Department of Histopathology, Cambridge University NHS Foundation Trust, Cambridge, United Kingdom.
  1. Address correspondence and reprint requests to Christine Parkinson, Department of Oncology, Cambridge University NHS Foundation Trust, Box 193, Hills Rd, Cambridge, CB2 0QQ, United Kingdom. E-mail: christine.parkinson{at}cruk.cam.ac.uk.

Abstract

Objective Primary platinum-resistant epithelial ovarian cancer (EOC) is an area of unmet medical need. There is limited evidence from small studies that platinum-based combinations can overcome “resistance” in a proportion of patients. We investigated the efficacy and toxicity of platinum-based combination chemotherapy in the platinum-resistant and platinum-refractory setting.

Methods Epirubicin, cisplatin, and capecitabine (ECX) combination chemotherapy was used at our institution for the treatment of relapsed EOC. From the institutional database, we identified all patients with primary platinum-refractory or platinum-resistant relapse treated with ECX as second-line therapy between 2001 and 2012. We extracted demographic, clinical, treatment, and toxicity data and outcomes. We used logistic and Cox regression models to identify predictors of response and survival respectively.

Results Thirty-four 34 patients (8 refractory, 26 resistant) were treated with ECX. Response Evaluation Criteria In Solid Tumors (RECIST) response rate was 45%, median progression-free survival (PFS) was 6.4 months, and overall survival (OS) was 10.6 months. Platinum-resistant patients had better outcomes than did platinum-refractory patients (response rate, 54% vs 0%, P = 0.047; PFS 7.2 vs 1.8 months, P < 0.0001; OS 14.4 vs 3 months, P < 0.001). In regression models, time to progression after first-line treatment and platinum-refractory status were the strongest predictors of response and PFS or OS, respectively. Patients with time to progression after first-line treatment longer than 3 months showed PFS and OS of 7.9 and 14.7 months, respectively. Toxicity was manageable, with only 13% of cycles administered at reduced doses.

Conclusions Epirubicin, cisplatin, and capecitabine seems to be active in platinum-resistant relapsed EOC with manageable toxicity. Further prospective investigation of platinum-anthracycline combinations is warranted in patients who relapse 3 to 6 months after first-line platinum-taxane treatment.

  • Ovarian cancer
  • Platinum refractory
  • Platinum resistant
  • Chemotherapy

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Footnotes

  • Ioannis Gounaris has received honoraria and support to attend conferences from PharmaMar which is unrelated to this work. The remaining authors declare no relevant conflicts of interest.

  • Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.ijgc.net).