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Background/Objectives: Platinum-resistant ovarian cancer (PROC) is a major therapeutic challenge, as it responds poorly to standard platinum-based treatment, has limited treatment options, and offers a generally unfavorable prognosis. Chemotherapeutic agents like pegylated liposomal doxorubicin (PLD), topotecan (TOPO), and gemcitabine (GEM) are used for this setting, but with varying efficacy and toxicity profiles, leading to an increasing need to understand the optimal balance between treatment effectiveness and tolerability for improving patient outcomes. This study evaluates the efficacy and side effects of PLD, TOPO, and GEM, focusing on progression-free survival (PFS), overall survival (OS), and safety profiles. Methods: We conducted a retrospective observational study that included 856 PROC patients treated with PLD (n = 383), TOPO (n = 352), or GEM (n = 121) at the OncoHelp Oncology Center from January 2018 to December 2023. Inclusion criteria encompass diagnosis, prior platinum therapy, and Eastern Cooperative Oncology Group (ECOG) status (0–2). Treatment protocols followed standard dosing, with adjustments for toxicity. Primary endpoints included PFS and OS, with safety assessed by incidence of grade 3 and 4 toxicities per CTCAE v5.0. Kaplan–Meier analysis and Cox regression were used to compare survival, and statistical significance was set at p < 0.05. Results: TOPO showed higher toxicity than PLD and GEM, including liver damage, hematological and non-hematological side effects, while PLD induced more skin toxicity. In terms of survival, minor differences were seen between the three chemotherapeutic agents, with a slight advantage for PLD for better disease control. Conclusions: Given the comparable results in OS across the regimens, treatment decisions should be based on other factors such as patient tolerance and quality of life. [ABSTRACT FROM AUTHOR]

Weekly paclitaxel (WP) is a chemotherapeutic cornerstone in the management of patients with platinum-resistant ovarian carcinoma. Multiple WP dosing regimens have been used clinically and studied individually. However, no formal comparison of these regimens is available to provide objective guidance in clinical decision making. The primary objective of this study was to compare the cumulative dose of paclitaxel delivered using 80 mg/m2/week, administered using either a 3 weeks out of 4 (WP3) or a 4 weeks out of 4 (WP4) regimen. The secondary objective was to evaluate the clinical outcomes associated with both regimens, including efficacy and toxicity parameters. Our retrospective cohort comprised 149 patients harboring platinum-resistant ovarian cancer treated at the CHU de Québec from January 2012 to January 2023. WP3 and WP4 reached a similar cumulative dose (1353.7 vs. 1404.2 mg/m2; p = 0.29). No significant differences in the clinical outcomes were observed. The frequency of dose reduction was significantly higher for WP4 than WP3 (44.7% vs. 4.9%; p < 0.01), mainly due to treatment intolerance from toxicity (34.0% vs. 3.9%; p < 0.01). Our data suggest that a WP3 regimen delivers a similar cumulative dose to WP4, hence offering a better efficacy profile without compromising efficacy. [ABSTRACT FROM AUTHOR]

Simple Summary: Antibody-drug conjugates (ADCs) are a promising new treatment modality for patients with cancer. They have been approved by the US Food and Drug Administration for treating breast, gastric, cervical, and ovarian cancers (OC), as well as lymphoma and multiple myeloma. Recently, several ADCs have undergone clinical trials for OC, and their development is underway. Several unmet medical needs exist in OC, including treatment for patients with platinum recurrence. This new treatment modality may benefit these patients. ADCs, a new concept of agents, comprise an antibody, a linker, and a payload. If the target is expressed in tumors, the payload specifically reaches the tumor cells. This approach is particularly suitable for OC because of its heterogeneous nature. In this review, we describe the existing evidence for ADC use in OC treatment and discuss ongoing clinical trials. Ovarian cancer (OC), accounting for approximately 200,000 deaths worldwide annually, is a heterogeneous disease showing major differences in terms of its incidence, tumor behavior, and outcomes across histological subtypes. In OC, primary chemotherapy, paclitaxel carboplatin, bevacizumab, and PARP inhibitors have shown prolonged progression-free survival and a favorable overall response rate compared to conventional treatments. However, treatment options for platinum-resistant recurrence cases are limited, with no effective therapies that significantly prolong the prognosis. Recently, mirvetuximab soravtansine, an alpha-folate receptor (FRα)-targeted antibody-drug conjugate (ADC), was approved by the US Food and Drug Administration for patients with FRα-positive recurrent epithelial OC (EOC). This approval was based on a Phase II study, which demonstrated its efficacy in such patients. ADCs comprise an antibody, a linker, and a payload, representing new concept agents without precedence. Advanced clinical studies are developing ADCs for patients with OC, targeting solid tumors such as gynecologic cancer. Ongoing clinical trials are evaluating ADCs targeting FRα and human epidermal growth factor receptor 2, trophoblast cell surface antigen-2, sodium-dependent phosphate transport protein 2B, and cadherin-6 in Phase II/III studies. In this review, we summarize the existing evidence supporting the use of ADCs in OC, discuss ongoing clinical trials and preclinical studies, and explore the potential of these innovative agents to address the challenges in OC treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: While latest evidence suggests that some patients with recurrent high-grade serous ovarian cancer may profit from reinduction with platinum-based chemotherapy regimens, the selection of patients who are likely to respond remains difficult. The present study therefore aimed to adapt a mathematical model, which used frequently available laboratory values to estimate growth rates of recurring tumors as an objectifiable surrogate of both therapy response and patient survival. After clinical validation, the model may help to personalize treatment strategies and thereby increase survival of affected patients. This study aimed to assess the predictive value of tumor growth rate estimates based on serial cancer antigen-125 (CA-125) levels on therapy response and survival of patients with recurrent high-grade serous ovarian cancer (HGSOC). In total, 301 consecutive patients with advanced HGSOC (exploratory cohort: n = 155, treated at the Medical University of Vienna; external validation cohort: n = 146, from the Ovarian Cancer Therapy–Innovative Models Prolong Survival (OCTIPS) consortium) were enrolled. Tumor growth estimates were obtained using a validated two-phase equation model involving serial CA-125 levels, and their predictive value with respect to treatment response to the next chemotherapy and the prognostic value with respect to disease-specific survival and overall survival were assessed. Tumor growth estimates were an independent predictor for response to second-line chemotherapy and an independent prognostic factor for second-line chemotherapy use in both univariate and multivariable analyses, outperforming both the predictive (second line: p = 0.003, HR 5.19 [1.73–15.58] vs. p = 0.453, HR 1.95 [0.34–11.17]) and prognostic values (second line: p = 0.042, HR 1.53 [1.02–2.31] vs. p = 0.331, HR 1.39 [0.71–2.27]) of a therapy-free interval (TFI) < 6 months. Tumor growth estimates were a predictive factor for response to third- and fourth-line chemotherapy and a prognostic factor for third- and fourth-line chemotherapy use in the univariate analysis. The CA-125-derived tumor growth rate estimate may be a quantifiable and easily assessable surrogate to TFI in treatment decision making for patients with recurrent HGSOC. [ABSTRACT FROM AUTHOR]

Ovarian cancer is a highly deadly malignancy in which recurrence is considered incurable. Resistance to platinum-based chemotherapy bodes a particularly abysmal prognosis, underscoring the need for novel therapeutic agents and strategies. The use of mithramycin, an antineoplastic antibiotic, has been previously limited by its narrow therapeutic window. Recent advances in semisynthetic methods have led to mithramycin analogs with improved pharmacological profiles. Mithramycin inhibits the activity of the transcription factor Sp1, which is closely linked with ovarian tumorigenesis and platinum-resistance. This article summarizes recent clinical developments related to mithramycin and postulates a role for the use of mithramycin, or its analog, in the treatment of platinum-resistant ovarian cancer. [ABSTRACT FROM AUTHOR]