Efficacy and Safety of Placebo During the Maintenance Therapy of Ovarian Cancer in Randomized Controlled Trials: A Systematic Review and Meta-analysis.

Introduction: This meta-analysis evaluated the efficacy and safety of placebo during the maintenance therapy of ovarian cancer (OC) patients in randomized controlled trials (RCTs). Methods: A comprehensive literature review was performed for RCTs published up to and including August 2020 from four electronic databases. We analyzed the efficacy and safety in the control arms of the maintenance therapy in advanced OC patients. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) of progression-free survival (PFS) and overall survival (OS) were estimated in the placebo arms and the observation arms, respectively, using the Frequency Framework method. We also calculated the incidences of common adverse effects (AEs) in the placebo arms. Results: In total, 41 articles with 20,099 (4,787 in the placebo arms, 3,420 in the observation arms, and 11,892 in the experiment arms) patients were included in this meta-analysis. Compared with observation, placebo did not improve or reduce PFS (HR, 1.02; 95% CI, 0.87-1.20; P = 0.81) and OS (HR, 1.02; 95% CI, 0.89-1.16; P = 0.76) of OC patients, while other treatments, except for radiotherapy, significantly improved PFS and OS (all P < 0.05). The incidences of AEs produced by placebo were 94.03% in all grades and 20.22% in grade ≥3. The incidences of AEs were 29.75% in fatigue, 26.38% in nausea, 24.34% in abdominal pain, 18.92% in constipation, 16.65% in diarrhea, 14.55% in vomiting, 13.89% in hypertension, and 13.14% in headache. Conclusions: Placebo did not improve or reduce the PFS and OS benefits of OC patients in RCTs but increased the incidences of AEs.

Selective estrogen receptor modulator with estrogen does not affect the proliferation and apoptosis of uterine leiomyoma cells.

BACKGROUND: The administration of menopausal hormone therapy (MHT) in women with uterine leiomyomas is still debated. The purpose of this article is to study the proliferation and apoptosis of uterine leiomyoma cells under the impact of selective estrogen receptor modulator (SERM) combined with estrogen. METHODS: Primary cultured uterine leiomyoma cells in the perimenopausal period were treated with estrogen (17-beta estradiol) + SERM (raloxifene) as the tissue selective estrogen complex (TSEC) group, while both estrogen + medroxyprogesterone acetate (E+P) and estrogen (E) alone as were used as control groups. The expression of proliferating cell nuclear antigen (PCNA) and B-cell lymphoma-2 (Bcl-2) proteins was assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and western-blot analysis, respectively. RESULTS: The proliferation in the TSEC group was weaker than the control groups (P<0.001). There was no statistical difference between the TSEC and blank control group on cell proliferation at 72 h (P=0.13). However, there was a significant difference between the other groups (P<0.001). PCNA expression of TSEC was lower than that of the E + P and E groups (P<0.05). There was no statistical difference in the expression of PCNA between the TSEC and blank control groups (P=0.63). Bcl-2 expression of TSEC was lower than that of the E + P and E groups (P<0.05). There was no statistical difference in the expression of Bcl-2 between the TSEC group and the blank control group (P=0.60). CONCLUSIONS: SERM combined with estrogen may have a better safety for perimenopausal women with uterine leiomyoma in MHT.