Bram H. Goldstein

Clinical differences among the PARP inhibitors in the first-line treatment of advanced-stage ovarian carcinoma

Despite favorable patient response rates to first-line chemotherapy, 5-year overall survival rates in ovarian cancer are dismal. Fortunately, the inclusion of PARP inhibitors (e.g. olaparib, niraparib, and rucaparib) following the completion of primary induction chemotherapy, has conferred improved progression-free survival rates. There are treatment outcome differences among the various PARP inhibitors that coincide with a patient's specific homologous recombination deficit (HRD) status; moreover, only single-agent olaparib and olaparib with bevacizumab have conferred a 5-year overall survival benefit. In the current review, we recount the clinical differences associated with the available PARP inhibitors in the management of advanced-stage ovarian carcinoma. The inclusion of PARP inhibitors has significantly improved survival benefits in advanced-stage ovarian cancer, especially among patients with an identifiable HRD. While there are tolerability differences inherent to the specific PARP inhibitors, not to mention approval distinctions, olaparib is the only PARP inhibitor that has demonstrated consistent overall survival benefits.

Statin use and ovarian cancer outcomes

Ovarian cancer contributed to 13,270 patient deaths in the United States during 2023 and is considered the most aggressive gynecologic malignancy. While surgery, chemotherapy and targeted medications have improved ovarian cancer patient outcomes, novel therapies that further bolster treatment efficacy without compromising toxicity represent an unmet clinical need. In the current review, we assessed the reported studies involving statin use and ovarian cancer outcomes; a preponderance of the evidence indicated that statins confer a survival benefit in ovarian cancer, especially for patients who underwent treatment post-diagnosis and for a prolonged interval. The evidence involving a potential survival benefit from statin use in ovarian cancer remains controversial, especially with hydrophilic statins (e.g. pravastatin). While statin users may exhibit better ovarian cancer survival outcomes than non-statin users, additional research should evaluate the putative clinical benefits of statins in ovarian cancer via randomized controlled trials.

A retrospective study comparing the efficacy of dose-dense chemotherapy, intraperitoneal chemotherapy and dose-dense chemotherapy with hyperthermic intraperitoneal chemotherapy in the treatment of advanced stage ovarian carcinoma

Hyperthermic intraperitoneal chemotherapy (HIPEC), intraperitoneal chemotherapy (IP) and dose-dense (DD) chemotherapy have been employed with varying success in the treatment of advanced stage ovarian carcinoma. Despite the clinical benefits associated with these specific forms of chemotherapy administration, they have not been comparatively analyzed, vis-à-vis their efficacy. Advanced stage ovarian cancer patients who were treated with platinum/taxane chemotherapy via a DD regimen (n = 100), IP approach (n = 81) or a DD regimen in conjunction with HIPEC (n = 64) were retrospectively evaluated. The clinical variables of interest were patient age, body mass index, surgery and pathology data, chemotherapy regimen, inclusion of maintenance therapy, and progression free/overall survival. Progression free survival (PFS) was significantly more pronounced in the HIPEC (34.9 months) and IP (34.0 months) patients, compared to the DD group (27.6 months) (P = 0.005). A cox-proportional hazards regression model indicated that there was a decreased risk of disease progression accorded to the patients who were treated with IP chemo or HIPEC and DD chemotherapy (HR, 0.43; 95 % CI: 0.21-0.88; P = 0.022) and the subjects who underwent optimal cytoreductive surgery (HR, 2.42; 95 % CI: 1.22-4.80; P = 0.011). Positive BRCA status (HR, 0.434; 95 % CI: 1.59-3.44; P = 0.001) and number of chemotherapy regimens (HR, 1.36; 95 % CI: 1.159-1.61; P = 0.001) were significantly correlated with improved OS although we did not discern a survival benefit associated with any of the chemotherapy treatments (P = 0.136). We observed PFS advantages conferred to the ovarian cancer patients treated with HIPEC and IP chemotherapy compared to DD chemotherapy. However, an overall survival advantage related to the chemotherapy regimens was not borne out, possibly due to the retrospective nature of the study or differing time periods wherein the specific patient cohorts underwent treatment.

Talc powder and ovarian cancer: what is the evidence?

Talc is a desiccant that has been historically used as baby powder by numerous women to enhance their feminine hygiene. Talc has been identified in proximity to asbestos; accordingly, retrospective and case-control studies have implicated the role of talc use in the development of ovarian cancer, whereas prospective evaluations have not documented concordant findings. Moreover, the positive associations derived from case-control studies have been remote and the putative causal factors remain inconclusive. Consequently, one should be circumspect regarding the assertion that genital talc powder application induces ovarian cancer development.