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Original research
Metronomic oral cyclophosphamide in relapsed ovarian cancer
  1. Pavlina Spiliopoulou1,2,
  2. Samantha Hinsley2,
  3. Iain A McNeish3,
  4. Patricia Roxburgh1,2 and
  5. Ros Glasspool1,2
  1. 1 Beatson West of Scotland Cancer Centre, Glasgow, UK
  2. 2 Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
  3. 3 Imperial College London Department of Surgery and Cancer, London, UK
  1. Correspondence to Dr Pavlina Spiliopoulou, Beatson West of Scotland Cancer Centre, Glasgow G12 0YN, UK; pavlina.spiliopoulou{at}glasgow.ac.uk

Abstract

Objectives To describe the clinical activity of metronomic cyclophosphamide in a population of patients with recurrent ovarian cancer, and to identify predictors of clinical response.

Methods We retrospectively reviewed all patients treated at our institution with oral metronomic cyclophosphamide for relapsed ovarian cancer between January 2012 and December 2016. These were identified from electronic chemotherapy prescription records. The primary endpoint was response rate by combined Gynecologic Cancer InterGroup (GCIG) criteria. Data on patient demographics, previous therapies, platinum resistance, germline BRCA1/2 (gBRCA1/2) status, disease response by radiological or cancer antigen 125 (CA125) criteria alone, adverse events secondary to metronomic cyclophosphamide treatment, progression-free survival, and overall survival were also evaluated.

Results 50 out of 68 patients treated with oral metronomic cyclophosphamide were evaluable for disease response. By combination criteria (radiological plus CA125), complete response was 0%, partial response 32%, stable disease 16%, and progressive disease 52%. In the intention-to-treat population (n=68), progression-free survival and overall survival were 2.6 months and 6 months, respectively. Having a gBRCA1/2 mutation reduced the risk of disease progression by radiological criteria (OR 0.07, 95% CI 0.008 to 0.67, p=0.02), and patients with gBRCA1/2 mutations had improved progression-free survival (7.9 vs 2.5 months, HR 0.4, 95% CI 0.23 to 0.74, p=0.003) and overall survival (15.5 vs 6 months, HR 0.49, 95% CI 0.28 to 0.85, p=0.02) with metronomic cyclophosphamide when compared with patients without gBRCA1/2 mutations (or unknown gBRCA1/2 status).

Conclusion Oral metronomic cyclophosphamide showed a clinical benefit in 48% of patients with recurrent ovarian cancer. gBRCA1/2 status can be an independent predictor of response.

  • ovarian cancer
  • BRCA1 protein
  • BRCA2 protein

Data availability statement

Data are stored in a de-identified form and can become available upon request to pavlina.spiliopoulou@glasgow.ac.uk.

https://doi.org/10.1136/ijgc-2021-002467

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    Data availability statement

    Data are stored in a de-identified form and can become available upon request to pavlina.spiliopoulou@glasgow.ac.uk.

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    Footnotes

    • Presented at Part of the study results were presented as a poster in the conference, American Association for Cancer Research, Addressing Critical Questions in Ovarian Cancer Research and Treatment, Pittsburgh, Pennsylvania (DOI: 10.1158/1557-3265.OVCA17-B02), October 2017.

    • Contributors PS: concept, data analysis, manuscript writing, statistical analysis. SH: statistical support. IMcN, manuscript writing and review. PR: concept, manuscript writing and review. RG: concept, manuscript writing and review.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.