Metronomic oral cyclophosphamide in relapsed ovarian cancer
File(s)Manuscript_IJGC_resubmission_210422.docx (675.96 KB)
Accepted version
Author(s)
Spiliopoulou, Pavlina
Hinsley, Samantha
McNeish, Iain A
Roxburgh, Patricia
Glasspool, Ros
Type
Journal Article
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.
Date Issued
2021-05-20
Date Acceptance
2021-05-07
Citation
International Journal of Gynecological Cancer, 2021, 31 (7), pp.1037-1044
ISSN
1048-891X
Publisher
BMJ Publishing Group
Start Page
1037
End Page
1044
Journal / Book Title
International Journal of Gynecological Cancer
Volume
31
Issue
7
Copyright Statement
© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.
License URL
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
Ovarian Cancer Action
National Institute for Health Research
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/34016703
PII: ijgc-2021-002467
Grant Number
RDB01
n/a
NIHR202372
Subjects
BRCA1 protein
BRCA2 protein
ovarian cancer
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2021-05-20