European Journal of Clinical Pharmacology

Lipid-lowering medication use and cancer-specific survival among endometrial or lung cancer patients: an Australian nationwide cohort study

Inconsistent results of lipid-lowering medications (LLMs) on improved cancer survival need more investigations. We tested the hypothesis that adherence to the drug would be associated with a lower cancer-specific mortality in a homogeneous population who has ever used the drug. Utilising data from the Australian Cancer database, linked to the Pharmaceutical Benefits Scheme data and the National Death Index, we identified two separate cohorts of 4519 and 3083 women patients with newly diagnosed endometrial and lung cancer respectively between 2003 and 2013. Adherence to this drug was calculated by proportion of days covered. Cox regression models with time-varying covariates were used to estimate the multivariable-adjusted cause-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of adherence to LLMs, statins, lipophilic and hydrophilic statins, and cancer-specific mortality. Each 10% increase in 1-year adherence to LLMs reduced cancer-specific mortality among women with endometrial cancer (adjusted HR=0.93, 95% CI 0.90-0.96) or lung cancer (adjusted HR=0.95, 95% CI 0.93-0.97). The inverse associations remained unchanged in different subgroup analyses. The reductions in lung cancer mortality were not apparent for women who adhered to lipophilic statins albeit better endometrial cancer survival appeared in the lipophilic statin group and borderline statistical improvement in the hydrophilic statin group. Among LLM users, adherence to this drug is inversely associated with reduced cancer-specific mortality. Together with previous evidence, randomised controlled trials are called for to confirm whether LLMs could be considered as an adjuvant treatment to improve prognosis.

Use of statins and risks of ovarian, uterine, and cervical diseases: a cohort study in the UK Biobank

Abstract Purpose To examine the associations between use of statins and risks of various ovarian, uterine, and cervical diseases, including ovarian cancer, endometrial cancer, cervical cancer, ovarian cyst, polycystic ovarian syndrome, endometriosis, endometrial hyperplasia, endometrial polyp, and cervical polyp. Methods We conducted a cohort study among female participants in the UK Biobank. Information on the use of statins was collected through verbal interview. Outcome information was obtained by linking to national cancer registry data and hospital inpatient data. We used Cox proportional hazards regression to examine the associations. Results A total of 180,855 female participants (18,403 statin users and 162,452 non-users) were included. Use of statins was significantly associated with increased risks of cervical cancer (adjusted hazard ratio (HR), 1.55; 95% confidence interval (95% CI), 1.05–2.30) and polycystic ovarian syndrome (adjusted HR, 4.39; 95% CI, 1.68–11.49). However, we observed no significant association between use of statins and risk of ovarian cancer, endometrial cancer, ovarian cyst, endometriosis, endometrial hyperplasia, endometrial polyp, or cervical polyp. Conclusion Our findings suggest that use of statins is associated with increased risks of cervical cancer and polycystic ovarian syndrome, but is not associated with increased or decreased risk of ovarian cancer, endometrial cancer, ovarian cyst, endometriosis, endometrial polyp, or cervical polyp.

A systematic literature review assessing if genetic biomarkers are predictors for platinum-based chemotherapy response in ovarian cancer patients

Ovarian cancer is the deadliest of gynecologic malignancies with the 5-year overall survival rate remaining at approximately 30%, a rate that has not improved over the last three decades. Standard of care for epithelial ovarian cancer patients consists of a platinum compound with a taxane given intravenously following debulking surgery; however, 80% of cases relapse within 2 years of diagnosis. This review sought to identify key underlying biomarkers related to platinum resistance in ovarian cancer to establish possible prognostic biomarkers of chemoresponse. A systematic literature review was conducted across three databases PubMed, EMBASE and SCOPUS to summarise the evidence for prognostic biomarkers in platinum-resistant ovarian cancer patients. Forty-eight human studies were used in the review encompassing 6719 participants in retrospective and prospective study designs. A total of 68 biomarkers were reported that were significantly correlated with chemoresponse and/or survival reporting a p value less than or equal to 0.05. This review accentuates the pleiotropic phenotypic complexities related to the response to platinum therapy in ovarian cancer. A one-size-fits-all approach may be ineffective in a large portion of patients, emphasising the need for a whole system-based approach and personalised treatment strategies. Identifying key biomarkers to aid clinical decision-making is the first essential step in developing and appropriating therapies for at-risk patients, reducing toxicity and improving quality of life.

Association between antidepressant use and gynecological cancer risk: a systematic review and meta-analysis

The potential carcinogenic effects of antidepressants (ADs) have been debated, with some preclinical studies suggesting associations with tumor promotion. However, clinical evidence regarding their impact on the risk of gynecological cancers remains limited and inconclusive, necessitating further investigation. Therefore we conducted a comprehensive search in PubMed, Embase, and Web of Science for studies examining the correlation between AD use and the risk of gynecological cancers. The DerSimonian and Laird random-effects model was applied to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the I-squared and Tau-squared statistics. Statistical analyses were performed using R software (version 4.4.1), with a significance threshold of p < 0.05. Our meta-analysis included 10 case-control studies, with a total of 965,834 participants, of whom 45,998 were AD users. The findings revealed a significant association between AD use and a reduced overall risk of gynecological cancers (OR = 0.9518; 95% CI: 0.9206 to 0.9841; P = 0.004; I Our meta-analysis indicates that AD use may serve as a protective factor against the development of gynecological cancers. However, potential biases and confounders should be considered, highlighting the need for balanced prescribing, taking into account the potential side effects of each AD and its suitability for individual patients.