Effectiveness and toxicity of metronomic oral cyclophosphamide for recurrent or platinum-refractory ovarian cancer: A meta-analysis

PURPOSE: To systematically assess the effectiveness and toxicity of metronomic oral cyclophosphamide (MOC) on recurrent or platinum-refractory ovarian cancer. METHODS: We searched the Cochrane Library, Embase, PubMed, CNKI, Weipu, and Wanfang databases for eligible studies. A descriptive statistical method was used to analyze the pooled results. Ratios and means were merged to analyze the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and the rate of serious adverse events (SAEs). Subgroup analysis, sensitivity analysis, and examination of publication bias were conducted for heterogeneity test and quality assurance of the results. RESULTS: The ORR and DCR by MOC were 25% (95% CI 12–41) and 61% (95% CI 43–77), respectively. The median PFS and OS were 4.29 months (95% CI 2.62–5.97) and 11.26 months (95% CI 8.13–14.39), respectively. The rate of SAEs was 41% (95% CI 30–52). The most frequent SAEs were gastrointestinal toxicity 6% (95% CI 1–12), lymphopenia 6% (95% CI 1–13), and neutropenia 5% (95% CI 2–9). In the subgroup analysis, the ORR and DCR in the subgroup of MOC combined with bevacizumab/pazopanib were 42% (95% CI 26–58) and 82% (95% CI 63–95), respectively. The median PFS and OS were 7.32 months (95% CI 5.93–8.70) and 17.35 months (95% CI 12.89–21.82), respectively. CONCLUSION: MOC has a certain effect in clinical response on patients with recurrent or platinum-refractory ovarian cancers, especially when MOC combined with bevacizumab/pazopanib. However, there is a high risk of SAEs.