Assessment of the efficacy and safety of anlotinib for the treatment of recurrent epithelial ovarian cancer.

OBJECTIVE: The current research aims to evaluate the efficacy and safety of anlotinib, an orally administered small-molecular tyrosine kinase inhibitor (TKI), in the treatment of recurrent epithelial ovarian cancer (EOC). METHODS: Patients with recurrent EOC subjected to treatment with anlotinib in Fourth Hospital of Hebei Medical University from 2020 to 2022 were included. The evaluation involved a thorough review of medical records, focusing on parameters such as the objective response rate (ORR), disease control rate (DCR), survival outcomes, and safety profile. RESULTS: This study recorded 51 patients, with 26 patients undergoing anlotinib monotherapy. The median progression-free survival (PFS) was 4.0 months, whereas the median overall survival (OS) was not reached. Seven cases underwent a combined treatment of anlotinib with chemotherapy. Among them, two patients achieved partial response (PR), two were categorized as stable disease (SD), and three were identified as having progressive disease (PD). The ORR and DCR were 28.5% (2/7) and 57.1% (4/7), respectively. Additionally, 18 cases received anlotinib maintenance therapy, and the median PFS and the median OS were 7.0 months and 25.5 months, respectively. The most prevalent adverse effects included fatigue (38.6%), hypertension (27.3%), nausea and vomiting (25.0%) and hand-foot syndrome (25.0%). CONCLUSION: Anlotinib demonstrated mild efficacy in the treatment of recurrent EOC, whether employed as monotherapy, chemotherapy-combined therapy, or maintenance therapy. The safety profile was proven manageable and well-tolerated, suggesting that anlotinib may emerge as a viable and novel treatment option for recurrent EOC.

Recurrent ovarian cancer in Africa: Rate and associated factors at a gynecologic oncology treatment center in Ethiopia-A cross-sectional study.

OBJECTIVE: To determine the recurrence rate of epithelial ovarian cancer (EOC) and associated factors in an Ethiopian tertiary setting. METHODS: A cross-sectional study was conducted on recurrent ovarian cancer at St. Paul's College Millennium Medical College (Ethiopia). Data were collected through chart review using a structured questionnaire. SPSS version 26 was used to analyze the data. Descriptive analysis, bivariate, and multivariate regression analysis were performed as appropriate. Percentages, frequencies, odds ratio with 95% confidence interval (CI) were used to present the results' significance. RESULTS: A total of 202 patients with EOC were reviewed. The recurrence rate of ovarian cancer (OC) among these patients was 86.1% (a total of 173 patients developed recurrent disease). The commonest site of recurrence was the pelvis (89.1%, 180/202) and the majority of patients with recurrence were platinum sensitive, accounting for 63.8% (129/202) of cases. Age ≥40 years (adjusted odds ratio [AOR], 23.3, CI: 4.3-31.5), macroscopic residual disease (AOR, 5.2, CI: 1.96-17.68), and FIGO Stage III/IV (AOR, 22.11, CI: 8.3-39.13) were associated with recurrence. CONCLUSION: The recurrence rate of OC in this study was higher than previous reports. Advanced age at first presentation, extent of residual disease after surgery, and FIGO Stage III and IV disease were associated with disease recurrence.

Surgery in Recurrent Ovarian Cancer: A Meta-Analysis.

Background: The second cytoreductive surgery performed for a patient who has recurrent ovarian cancer remains controversial. Our study analyzes overall survival (OS) and disease-free survival (DFS) for cytoreductive surgery in addition to chemotherapy in recurrent ovarian cancer instead of chemotherapy alone. Methods: A meta-analysis was conducted using PubMed and the Cochrane database of systematic reviews to select randomized controlled studies. In total, three randomized studies were used, employing a total of 1249 patients. Results: The results of our meta-analysis of these randomized controlled trials identified significant differences in OS (HR = 0.83, IC 95% 0.70-0.99, p < 0.04) and DFS (HR = 0.63, IC 95% 0.55-0.72, p < 0.000001). A subgroup analysis comparing complete cytoreductive surgery and surgery with residual tumor achieved better results for both OS (HR = 0.65, IC 95% 0.49-0.86, p = 0.002) and DFS (HR = 0.67, IC 95% 0.53-0.82, p = 0.0008), with statistical significance. Conclusions: A complete secondary cytoreductive surgery (SCS) in recurrent ovarian cancer (ROC) demonstrates an improvement in the OS and DFS, and this benefit is most evident in cases where complete cytoreductive surgery is achieved. The challenge is the correct patient selection for secondary cytoreductive surgery to improve the results of this approach.

Observation of the therapeutic effect of apatinib in advanced platinum-resistant recurrent epithelial ovarian cancer.

BACKGROUND: Apatinib is an oral anti-angiogenic drug that mainly targets vascular endothelial growth factor receptor 2 (VEGFR-2) and is widely used in a variety of solid tumours. The purpose of this study is to evaluate the clinical efficacy and safety of apatinib in patients with advanced platinum-resistant relapsed epithelial ovarian cancer (EOC). METHODS: A retrospective analysis was performed, the clinical data of patients with stage IIIC-IV platinum-resistant relapsed EOC between January 2014 and May 2018 were collected. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were reviewed and evaluated. The propensity score matching (PSM) method was used to determine the final case data included in this study. RESULTS: According to 1:2 propensity matching, 108 patients were finally taken into account: 36 in the apatinib group and 72 in the control group. The follow-up ended in January 2019, and the median follow-up time was 28 months. In the apatinib group, ORR was 30.56% and DCR was 66.67%, whereas in the control group, ORR was 16.67% and DCR was 44.44%. In the apatinib group, median PFS was 6.0 months (95% CI 3.69-8.31) and median OS was 15.8 months (95% CI 6.99-24.6), while in the control group, median PFS was 3.3 months (95% CI 2.44-4.16) and median OS was 9.2 months (95% CI 6.3-12.06); the difference was statistically significant (P < 0.05). Apatinib was more effective than conventional chemotherapy in reducing the risk of PFS [HR 0.40 (95% CI 0.22-0.76), P = 0.0017] and OS [HR 0.40 (95% CI 0.21-0.73), P = 0.002]. Multivariate Cox analysis showed that the course of treatment and decrease in serum CA125 levels are independent risk factors for PFS in patients, while apatinib, the length of treatment course and the location of the lesion are independent risk factors for recurrence affecting the OS of patients. The main grade 3-4 adverse events in the apatinib group were hypertension, hand-foot syndrome, and oral mucosal ulcers, and all adverse events were controllable. CONCLUSION: Apatinib was found to be both safe and effective in patients with advanced platinum-resistant relapsed EOC. More in-depth clinical research and applications should be carried out.

Efficacy and safety of fluzopril in the treatment of platinum-sensitive recurrent epithelial ovarian cancer / 新乡医学院学报

Objective To investigate the efficacy and safety of fluzopril in the treatment of platinum-sensitive recurrent epithelial ovarian cancer.Methods A total of 107 patients with platinum-sensitive recurrent epithelial ovarian cancer admitted to the First Affiliated Hospital of Henan University of Science and Technology from January 2019 to December 2020 were selected as the subjects.According to treatment methods,the patients were divided into control group(n=50)and observation group(n=57).The patients in the control group received a first-line chemotherapy regimen of paclitaxel combined with platinum:on the first day,intravenous infusion with paclitaxel injection 135 mg·m-2 was administered;on day 1-3,intravenous drip with cisplatin 50-60 mg·m-2 was administered;21 days was one chemotherapy cycle.On the basis of the treatment in the control group,the patients in the observation group were given fluzoparide capsules orally,150 mg each time,twice a day,and the treatment continued until disease progression or unacceptable toxic reactions occurred;21 days was one chemotherapy cycle.The patients in both groups received three consecutive chemotherapy cycles.The clinical efficacy,prognosis within 2 years after chemotherapy,Karnofsky Performance Status(KPS)score before and after chemotherapy,and incidence of adverse reactions during chemotherapy of patients between the two groups were compared.Results After 3 cycles of chemo-therapy,the disease control rate and objective remission rate of patients in the observation group were significantly higher than those in the control group(x2=5.420,4.220;P＜0.05).Following up to 24 months,the progression free survival of patients in the observation group was significantly longer than that in the control group(t=6.702,P＜0.05);there was no statistically significant difference in 1-year survival rate of patients between the two groups(x2=0.415,P＞0.05);the 2-year survival rate of patients in the observation group was significantly higher than that in the control group(x2=5.420,P＜0.05).Before chemotherapy,there was no statistically significant difference in KPS scores of patients between the two groups(t=0.537,P＞0.05);the KPS scores of patients in the two groups after three cycles of chemotherapy were significantly higher than those before chemotherapy(t=5.604,9.378;P＜0.05);after three cycles of chemotherapy,the KPS score of patients in the observation group was significantly higher than that in the control group(t=2.608,P＜0.05).The patients in both groups experienced hematological and non-hematological adverse reactions during chemotherapy;the main hematological adverse reactions was bone marrow suppression,most of which were Ⅲ ° and Ⅳ ° adverse reactions;the non-hematological adverse reactions included alo-pecia,gastrointestinal reactions,and liver and kidney dysfunction,most of which were Ⅰ°and Ⅱ°adverse reactions.There were no chemotherapy related deaths of patients in both groups.The incidence rates of anemia,thrombocytopenia,neutropenia,leuko-penia,lymphopenia,nausea,vomiting,fatigue,loss of appetite,hair loss,elevated serum creatinine,and elevated alanine amino-transferase(ALT)of patients during chemotherapy in the control group were 68.00％(34/50),72.00％(36/50),58.00％(29/50),68.00％(34/50),22.00％(11/50),26.00％(13/50),24.00％(12/50),46.00％(23/50),30.00％(15/50),50.00％(25/50),20.00％(10/50),10.00％(5/50),respectively;the incidence rates of anemia,thrombocytopenia,neutropenia,leukopenia,lymphopenia,nausea,vomiting,fatigue,loss of appetite,hair loss,elevated serum creatinine,and elevated ALT of patients during chemotherapy in the observation group were 61.40％(35/57),63.16％(36/57),49.12％(28/57),52.63％(30/57),21.05％(12/57),22.81％(13/57),24.56％(14/57),42.11％(24/57),29.82％(17/57),47.37％(27/57),21.05％(12/57),10.53％(6/57),respectively.There was no statistically significant difference in the incidences of anemia,thrombocytopenia,neutropenia,leukopenia,lymphopenia,nausea,vomiting,fatigue,loss of appetite,hair loss,elevated serum creatinine,and elevated ALT of patients during chemotherapy between the control group and the observation group(x2=0.047,0.000,0.041,0.694,0.056,0.000,0.208,0.041,0.184,0.160,0.233,0.102;P＞0.05).Conclusion For patients with platinum-sensitive recurrent ovarian cancer,the combination of paclitaxel and platinum chemo-therapy combined with fluzopril can effectively improve the anti-tumor effect,prolong the progression-free survival,improve survival rate and quality of life,and the adverse reactions are controllable.

Pharmacotherapeutic treatment options for recurrent epithelial ovarian cancer.

INTRODUCTION: Almost 80% of epithelial ovarian cancer present in advanced stage at diagnosis and despite excellent response to surgery and chemotherapy, more than 70% cancers recur. Subsequent therapies become decreasingly effective in controlling the disease, with each successful therapy being effective for a shorter duration. As a result, there is a need for novel therapeutic strategies to effectively treat recurrence. AREAS COVERED: In this extensive literature review of high-quality articles, we have focused on surveillance strategy to detect recurrence early, classification of recurrence based on timeline, role of surgery, chemotherapy, and targeted agents such as anti-angiogenetic drugs, PARP inhibitors, and immune checkpoint inhibitors in platinum-sensitive and platinum-resistant disease, respectively. EXPERT OPINION: Recurrent ovarian cancers (ROC) are represented by a heterogenous group of patient population in terms of platinum-free interval (PFI), histology, molecular characteristics and immune recognition. In today's era of precision medicine, chemotherapy should be combined with appropriate targeted agent in a multipronged approach to prolong survival and provide better quality of life outcomes by minimizing side effects.

Real-World Efficacy of Bevacizumab in Patients With Recurrent Epithelial Ovarian Cancer.

Background: Bevacizumab in combination with chemotherapy prolonged the progression-free survival (PFS) of patients with recurrent epithelial ovarian cancer (EOC) in large-scale randomized controlled trials. However, real-world data for the use of bevacizumab in Asian patients with EOC is lacking. This study investigated the efficacy of adding bevacizumab to chemotherapy and compared it with that of chemotherapy alone in patients with recurrent EOC using real-world data from an Asian population. Method: We conducted a retrospective cohort study using data from a tertiary medical center in central Taiwan. Patients who had EOC with first relapse between 2011 and 2019 were enrolled. Patients' medical histories, medication treatment, and relevant information were collected. The outcomes were PFS and overall survival (OS). The Kaplan-Meier plot was used to generate a survival curve for OS and PFS. Cox proportional hazard analysis was used to determine the associations of Bevacizumab treatment with OS and PFS with adjustment of relevant variables. Subgroup analyses were conducted to determine if there was a significant variation in the aforementioned associations. Results: After a median follow-up of 23 months, 67% of patients in the Bevacizumab group and 81% of patients in the non-Bevacizumab group had disease progression or death. There was no significant between-group difference in OS (p = 0.475). The median duration of PFS was 18.9 and 9.6 months, respectively, favoring those who were treated with Bevacizumab. After multivariate adjustment, treatment with Bevacizumab was associated with a lower risk of disease progression (hazard ratio 0.33, 95% CI 0.13-0.85, p = 0.021). The improvement in PFS was consistent in the subgroups of different histological types, different disease stages at diagnosis, different treatment-free intervals, those undergoing or not undergoing secondary cytoreductive surgery, diverse chemotherapy regimens. Conclusion: Our findings provided crucial insights into the efficacy of bevacizumab for the treatment of recurrent EOC in the real-world setting.

Improved prognosis for recurrent epithelial ovarian cancer by early diagnosis and 125I seeds implantation during suboptimal secondary cytoreductive surgery: a case report and literature review.

BACKGROUND: Epithelial ovarian cancer (EOC) has the worst prognosis in all of gynecologic malignant tumors because of its high recurrence and eventually chemo-resistance. Early diagnosis of recurrence is crucial to avoid diffuse dissemination. Failure of traditional treatment in recurrent epithelial ovarian cancer remains a challenge for clinicians. On the other hand, 125I brachytherapy has been accepted as a useful and hopeful treatment for multiple advanced cancers in recent years. However, its success in advanced epithelial ovarian cancer is limited. Here we report a case of recurrent ovarian cancer who had been early diagnosis of isolated recurrence and successfully treated with 125I seeds implantation during suboptimal cytoreductive surgery. CASE PRESENTATION: A 59-year-old woman presented with recurrent epithelial ovarian cancer who have had a history of ovarian cancer stage IIIB and an R0 resection had been achieved nearly 2 years before presented in our hospital. She underwent suboptimal secondary cytoreductive surgery after four cycles of chemotherapy with little effectiveness and severe chemotherapy-related side effects. Approximately 70% of the cancer-bulk was resected during surgery. For residual lesion which fixed around the right ureter and right external iliac vessel, 125I seeds implantation was performed. Postoperatively, the patient was treated with two cycles of combination chemotherapy with paclitaxel and carboplatin. The patient was free of disease at 26 months' follow-up period. CONCLUSION: In recurrent EOC patients with unresectable isolated lesion, salvage 125I seeds implantation are feasible and may contribute to survival.

Does sites of recurrence impact survival in secondary cytoreduction surgery for recurrent epithelial ovarian cancer?

Outcomes of secondary cytoreduction surgery (SCS) were evaluated for morbidity, progression free survival (PFS) and overall survival (OS) and factors influencing results were explored. Retrospective analysis of all cases of SCS for epithelial ovarian cancer (EOC) was performed from October 2010 to December 2017. 62 patients were prospectively identified as candidates for SCS and 57 underwent SCS. 20(35%) patients required bowel resection/s, 24(42%) had nodal resections and 11(19%) had extensive upper abdominal surgery. 51(89%) achieved complete cytoreduction. After a median follow-up of 30 months (range 9-95 months), median PFS was 32 months (CI 17-76 months) and median OS has not reached. Seventeen patients have died and 32 have progressed. Three patients had Clavien-Dindo grade-3 and two had grade-4 morbidity. Patients who had multi-site recurrence had shorter median PFS (p = 0.04) and patients who required bowel resections had lower median OS (p = 0.009) compared to rest of the cohort.IMPACT STATEMENTWhat is already known on this subject? Retrospective studies have confirmed survival advantage for recurrence in epithelial ovarian cancer and recommend SCS for carefully selected patients. This finding is being evaluated in randomised control trials currently.What do the results of this study add? This study presents excellent results for survival outcomes after SCS and highlights importance of careful selection of patients with a goal to achieve complete cytoreduction. In addition, for the first time in literature, this study also explores various factors that may influence results and finds that there are no differences in survival outcomes whether these patients had early stage or advanced stage disease earlier. Patients who have multisite recurrence tend to have shorter PFS but no difference were noted for overall survival. Patients who have recurrence in bowels necessitating resection/s have a shorter median OS compared to rest of cohorts, however, still achieving a good survival time.What are the implications of these findings for clinical practice and/or further research? These findings will raise awareness for the clinicians and patients while discussing surgical outcomes and would set an achievable standard to improve cancer services. The pattern of recurrence and associated outcomes also point towards difference in biological nature of recurrent disease and could provide an opportunity for scientists to study the biological makeup of these recurrent tumours.

Interval between secondary cytoreductive surgery and adjuvant chemotherapy is not associated with survivals in patients with recurrent ovarian cancer.

BACKGROUND: Secondary cytoreductive surgery (SCS) is possible in selected patients with recurrent epithelial ovarian cancer (EOC). The goal of SCS is complete resection, although chemotherapy is always followed. Delayed intervals between primary debulking surgery and adjuvant chemotherapy was reported to be associated with poorer survivals, however, the role of intervals in recurrent disease is still unknown. MATERIALS AND METHODS: This retrospective cohort study reviewed data from electronic medical records of women with recurrent EOC treated at Samsung Medical Centre, Seoul, Korea, between January 1, 2002, and December 31, 2015. Patients who underwent SCS with adjuvant chemotherapy for recurrent EOC were eligible. We defined intervals as the period between the day of SCS and the first cycle of adjuvant chemotherapy. RESULTS: Seventy-nine patients were eligible for this study. Their median age was 48 (range, 18-69) years and median interval between the date of SCS and initiation of adjuvant chemotherapy was 10 (range, 4-115) days. The rate of complete resection was 72.2% (57/79). Division of the patients by interval (Group 1, interval ≤ 10 days; Group 2, interval > 10 days) revealed no difference in clinical parameters. No gross residual disease after SCS (no vs. any gross residual, p = 0.002) and longer platinum-free survival (over 12 vs. 6-12 months, p = 0.023) were independent favorable prognostic factors in Cox model; however, the intervals did not affect survival. CONCLUSIONS: Delayed intervals to adjuvant chemotherapy after secondary cytoreductive surgery is not associated with decreased survivals. It is important to identify recurrent EOC patients who might have no gross residual disease following SCS. Moreover, surgeons should strive for complete resection.

Combined cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as a treatment for recurrent epithelial ovarian cancer-National Cancer Institute experience.

BACKGROUND: Complete cytoreduction has been associated with survival benefit in the treatment of recurrent epithelial ovarian cancer (EOC). In this study, the aim is to investigate the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of recurrent EOC. PATIENTS AND METHODS: This is a descriptive (case series) study including 9 patients with recurrent EOC treated by CRS and HIPEC. They were treated and followed up between December 2011 and December 2017. The study was performed at The National Cancer Institute (NCI) - Cairo University (CU). RESULTS: Postoperative death occurred in 2 cases, while recurrence occurred in one case. Six cases had smooth postoperative course and free follow-up. Median follow-up period was 39 months, ranging from 29 to 47 months. Median overall survival was 42 months while median disease-free survival was not reached. CONCLUSIONS: Treatment of recurrent EOC by CRS and HIPEC appears to be promising. However, this line of treatment requires further evaluations and larger studies for better assessment of the potential survival benefits and possible complications.

The role of pemetrexed in recurrent epithelial ovarian cancer: A scoping review.

Ovarian cancer is the leading cause of mortality among gynecologic malignancies, with most cases diagnosed at an advanced stage. Despite an initial response, most develop a recurrence and subsequent resistance to standard therapies. Pemetrexed (AlimtaTM) is a new generation multi-targeted antifolate initially approved for the treatment of malignant pleural mesothelioma. In recent years, it has shown promise in the treatment of recurrent epithelial ovarian cancer. In this review, we outline the current literature and discuss the future of pemetrexed in the setting of recurrent epithelial ovarian cancer.

Systemic therapy for recurrent epithelial ovarian cancer: a clinical practice guideline.

OBJECTIVE: The purpose of this guideline is to recommend systemic therapy options for women with recurrent epithelial ovarian cancer, including fallopian tube and primary peritoneal cancers. METHODS: This document updates the recommendations published in the 2011 Optimal Chemotherapy for Recurrent Ovarian Cancer guideline from Cancer Care Ontario. Draft recommendations were formulated based on evidence obtained through a systematic review of phase ii and iii randomized controlled trials (rcts). The draft recommendations underwent internal review by clinical and methodology experts, and external review by clinical practitioners through a survey assessing the clinical relevance and overall quality of the guideline. Feedback from the internal and external reviews was integrated into the clinical practice guideline. RESULTS: The primary literature search yielded thirty-six primary research papers representing thirty rcts that met the eligibility criteria. The guideline provides recommendations for patients with serous tumour histologies and with recurrent, platinum-resistant, and platinum-sensitive ovarian cancer. CONCLUSIONS: The body of evidence from trials that included olaparib and bevacizumab consistently shows a benefit in progression-free survival (pfs) without a corresponding benefit in overall survival (os). The Working Group for this guideline designated pfs, which is associated with symptom control, as a critical outcome. A finding of net benefit can therefore be concluded based on significant differences in pfs. However, that benefit is not without identified harms. Given the identified harms, patient involvement in the decision-making process must take into consideration the side effect profiles of olaparib and bevacizumab within the context of improved pfs but minimal change in os.

Secondary cytoreductive surgery in recurrent epithelial ovarian cancer: A prognostic analysis with 103 cases.

BACKGROUND: Due to satisfactory cytoreductive surgery combined with platinum-based chemotherapy in epithelial ovarian cancer has improved greatly, however, the relapse rate also high. In current study, we analyzed prognostic factors related to secondary cytoreductive surgery in patients with recurrent epithelial ovarian cancer. METHODS: Clinical and follow-up data from 103 patients with recurrent epithelial ovarian cancer who received secondary cytoreductive surgery and were admitted to our hospital between January 2000 and December 2008 were analyzed. RESULTS: Median survival after recurrence (RS) after the first relapse for the 103 patients was 36 months, and median overall survival (OS) was 60 months. Patients without visible residual tumors after secondary cytoreductive surgery had longer RS and OS compared to those with residual tumors ≥1 cm. The RS and OS of patients without visible residual tumors after secondary cytoreductive surgery were not significantly different compared to those with residual tumors between 0.1 and 1 cm. Patients with disease free interval (DFI) ≥ 12 months at secondary cytoreductive surgery had longer RS and OS compared to those with DFI < 12 months. Patients with one recurrent lesion had longer RS and OS compared to those with more than one lesion. CONCLUSIONS: Residual tumor at secondary cytoreductive surgery, DFI and number of lesions were independent prognostic factors for secondary cytoreductive surgery in patients with epithelial ovarian cancer. Patients with DFI ≥12 months and a single lesion had better prognosis for achieving satisfactory cytoreduction, especially the absence of visible residual tumors.

Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): Long-term survival, impact of ascites, and progression-free survival-2.

PURPOSE: Trebananib, a peptibody that blocks binding of angiopoietin-1 and -2 to Tie2, significantly prolonged progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer in the phase 3 TRINOVA-1 study. We report overall survival (OS) in the intent-to-treat population and clinically relevant subgroups and time to second disease progression (PFS-2). PATIENTS AND METHODS: Women with recurrent disease (platinum-free interval<12months) were randomized to receive intravenous paclitaxel 80mg/m(2) (3weeks on/1week off) plus intravenous trebananib 15mg/kg or placebo, weekly. OS in the intent-to-treat population was a key secondary endpoint. Exploratory analysis of PFS-2 was conducted according to guidance by the European Medicines Agency. RESULTS: Median OS was not significantly improved with trebananib compared with placebo (19.3 versus 18.3months; HR, 0.95; 95% CI, 0.81-1.11; P=0.52) in the intent-to-treat population (n=919). In subgroup analysis, trebananib improved median OS compared with placebo (14.5 versus 12.3months; HR, 0.72; 95% CI, 0.55-0.93; P=0.011) in patients with ascites at baseline (n=295). In the intent-to-treat population, trebananib significantly improved median PFS-2 compared with placebo (12.5 versus 10.9months; HR, 0.85; 95% CI, 0.74-0.98; P=0.024). The incidence and type of adverse events in this updated analysis was consistent with that described in the primary analysis; no new safety signals were detected. CONCLUSIONS: OS was not significantly longer in the intent-to-treat population, although there was an improvement in OS in patients with ascites receiving trebananib. PFS-2 confirmed that the PFS benefit associated with trebananib was maintained through the second disease progression independent of the choice of subsequent therapy.

Prognostic value of (18)F-FDG PET/CT volumetric parameters in recurrent epithelial ovarian cancer.

OBJECTIVE: Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from (18)F-FDG PET/CT are emerging prognostic biomarkers in various solid neoplasms. These volumetric parameters and the SUVmax have shown to be useful criteria for disease prognostication in preoperative and post-treatment epithelial ovarian cancer (EOC) patients. The purpose of this study was to evaluate the utility of (18)F-FDG PET/CT measurements to predict survival in patients with recurrent EOC. MATERIAL AND METHODS: Twenty-six patients with EOC who underwent a total of 31 (18)F-FDG PET/CT studies for suspected recurrence were retrospectively included. SUVmax and volumetric parameters whole-body MTV (wbMTV) and whole-body TLG (wbTLG) with a threshold of 40% and 50% of the SUVmax were obtained. Correlation between PET parameters and progression-free survival (PFS) and the survival analysis of prognostic factors were calculated. RESULTS: Serous cancer was the most common histological subtype (76.9%). The median PFS was 12.5 months (range 10.7-20.6 months). Volumetric parameters showed moderate inverse correlation with PFS but there was no significant correlation in the case of SUVmax. The correlation was stronger for first recurrences. By Kaplan-Meier analysis and log-rank test, wbMTV 40%, wbMTV 50% and wbTLG 50% correlated with PFS. However, SUVmax and wbTLG 40% were not statistically significant predictors for PFS. CONCLUSION: Volumetric parameters wbMTV and wbTLG 50% measured by (18)F-FDG PET/CT appear to be useful prognostic predictors of outcome and may provide valuable information to individualize treatment strategies in patients with recurrent EOC.

Comparison of bevacizumab alone or with chemotherapy in recurrent ovarian cancer patients.

BACKGROUND: To compare the efficacy of chemotherapy (C) combined with bevacizumab (Bev) versus Bev alone in recurrent, heavily pretreated epithelial ovarian cancer (EOC). METHODS: A multicenter analysis of patients treated from 2004 to 2011 was performed. Demographic, treatment, response, and adverse event information were obtained. Progression-free (PFS) and overall survival (OS) were analyzed. RESULTS: Of 277 patients (median age: 58years), the majority had Stage III and IV (86%) disease, and 72% had serous histology. 244 (88%) were treated with C+Bev and 33 (12%) with Bev. Corresponding median progression-free survival (PFS) was 8.7 and 6.7months, and median overall survival (OS) was 14.3 and 10.5months, respectively. The chemotherapeutic agents combined with Bev and the median OS include: pegylated liposomal doxorubicin (n=19, OS of 20.4months), taxanes (n=55, OS of 20.2months), gemcitabine (n=106, OS of 14.1months), topotecan (n=43, OS of 13months), and cyclophosphamide (n=21, OS of 13months). There was no significant difference in toxicities between the C+Bev vs. Bev alone group. CONCLUSION: This retrospective analysis supports that combination chemotherapy and bevacizumab prolongs PFS and OS compared with bevacizumab alone.

The use of weekly topotecan in the treatment of heavily pretreated recurrent epithelial ovarian and primary peritoneal cancer: the Kaohsiung Chang Gung experience.

OBJECTIVE: We attempted to investigate the safety and efficacy of alternative weekly topotecan dosing in a heavily pretreated Taiwanese population with recurrent epithelial ovarian cancer (EOC) and primary peritoneal carcinoma (PPC). MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients with recurrent EOC and PPC who had been treated with weekly topotecan between November 2008 and May 2012. Topotecan was given at a dose of 2.75-4 mg/m(2) via a 30-minute intravenous (IV) infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity occurred. RESULTS: Thirty-two patients were identified and 24 (75%) of them had received at least two previous regimens of chemotherapy; the median number of treatment courses was seven. The main toxicities (Grades 3 and 4) were anemia in seven (21.9%), neutropenia in six (18.8%), and thrombocytopenia in two patients (6.2%). No deaths were attributable to the therapy. Overall, seven patients (21.9%) showed a partial response (PR), while seven patients (21.9%) with stable disease (SD) were observed. Furthermore, we found a favorable response and toxicity profile in patients who received the lowest dose intensity (2.75 mg/m(2)). The median progression-free survival (PFS) and overall survival (OS) were 3 months [95% confidence interval (CI) 2.7-3.2] and 20 months (95% CI 11.1-28.9), respectively. CONCLUSION: Topotecan administered as a weekly dosage (2.75-4 mg/m(2)) seems to be a tolerable regimen with modest activity in a Taiwanese population. Although the lower dose schedule showed a higher response with a better toxicity profile, further studies with more cases are needed to confirm this finding.

External validation of two prediction models of complete secondary cytoreductive surgery in patients with recurrent epithelial ovarian cancer.

OBJECTIVE: The purpose of this study was to validate the performance of two prediction models, the AGO score and the Tian model, of complete secondary cytoreductive surgery (SCS) in patients with recurrent epithelial ovarian cancer. The predictive value of both models for survival controlled for the outcome of SCS was analyzed and known predictive factors for complete SCS were tested. METHODS: A population-based database with 408 patients, who underwent SCS between 2000 and 2013 in 38 Dutch hospitals, was used. The validation cohorts for the AGO score and the model of Tian contained 273 (66.9%) and 257 (63.0%) patients, respectively. RESULTS: The AGO score and Tian model showed a positive predictive value for complete SCS of 82.0% and 80.3% respectively, and a false negative rate of 68.5% and 55.6% respectively. A positive AGO score had no significant association with overall survival (HR 0.73; 95% CI 0.51-1.06) whereas the low risk score of the Tian model did (HR 0.62; 95% CI 0.41-0.93). A good performance status (OR 0.60; 95% CI 0.33-1.10) and the absence of ascites (OR 0.18; 95% CI 0.08-0.41) were prognostic factors for complete SCS. CONCLUSIONS: Both the AGO score and the model of Tian showed a high positive predictive value for complete SCS but also relatively high false negative rates. However, before the two prediction models can be applied in daily clinical practice the usefulness of SCS itself has to be proven first by the three ongoing randomized controlled trials: DESKTOP III trial, the GOG 213 trial and the Dutch SOCceR trial.

Epithelial ovarian cancer: A case report.

An 82-year-old female was diagnosed with ovarian cancer in May 2004. Following gynecological surgery, pathological evaluation showed stage IIIC epithelial ovarian cancer. From June 2004 to January 2005, the patient received six cycles of conventional treatment combined with intravenous paclitaxel (Taxol®) and cisplatin. The patient developed abdominal distension and experienced a gradual deterioration in health during 2007, with admission to The First Affiliated Hospital in May 2007. The patient presented with severe abdominal distension and breathing difficulty on May 15 and appeared to be in critical condition. Ultrasound examination revealed massive ascites and left-side pleural effusion. Thoracentesis and abdominocentesis were performed, and 300 mg carboplatin was administered intraperitoneally on May 19, followed by a second abdominocentesis on May 21. However, these treatments did not alleviate the symptoms, and 200 mg bevacizumab was administered by intravenous infusion on May 27. The condition of the patient gradually improved and 400 mg bevacizumab was administered by intravenous infusion every two weeks from June 9. From December, the dosage of bevacizumab was reduced to 200 mg every two weeks. In addition, 300 mg carboplatin was administered intraperitoneally on November 4 and intraperitoneal carboplatin chemotherapy was repeated thereafter. The patient exhibited disease-free survival until July 2009, at which time disease progression was observed and the cancer recurred in August 2009. The patient died of multiple organ failure in September 2009. Bevacizumab rapidly eliminated the patient's massive ascites and pleural effusion, and achieved an effect that was not possible with other treatments. Therefore, bevacizumab is an effective therapy for late-stage relapse and refractory ovarian cancer.