taxane and Carcinoma--Ovarian-Epithelial

Chemotherapy is the cornerstone of adjuvant therapy in ovarian cancer. Its impact on the quality of life (QoL) has been addressed in several studies; however, several misperceptions concerning this affect patient counseling and physicians' ability to overcome patient fears. In the present systematic review, we sought to accumulate current evidence in the field in order to help establish robust information that will help physicians answer patients' questions.. The present systematic review is based on the PRISMA guidelines. Studies that evaluated patient QoL pre-, during, and post-chemotherapy with the use of the QLQC-30 were selected for inclusion. Their methodological quality was assessed with the before-after studies tool that is proposed by the National Institute of Health (NIH).. Ten studies that involved 5181 patients were included in the present systematic review. The risk of bias and methodological quality of included studies was of good and fair overall quality. Retrieved data suggest there is substantial evidence that points toward improved global QoL among ovarian cancer patients treated with taxanes-platinum combination therapy. Individual outcomes evaluated with the QLQ-C30 also provide positive results, although underreporting was noted.. Despite the significant heterogeneity in outcome reporting, the findings of this study reveal the significant benefit of combined platinum taxane chemotherapy on the QoL of ovarian cancer patients and can be used for patients counseling in order to reduce refusals that arise from fear of adverse effects that may negatively affect QoL. Graphical abstract.

Topics: Bridged-Ring Compounds; Carcinoma, Ovarian Epithelial; Female; Humans; Ovarian Neoplasms; Platinum; Quality of Life; Taxoids

Intravenous (IV) chemotherapy has been compared with intraperitoneal (IP) chemotherapy in randomized clinical trials in advanced ovarian cancer (OC). The aim of this meta-analysis was to evaluate efficacy and toxicity of IV and IP and identify differences in outcomes.. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement was applied. Random-effects models were used. Primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and the proportion of patients with grade ≥2 acute toxicity.. Four randomized clinical trials representing 2461 patients were identified. The hazard ratio (HR) of PFS was 0.88 (95% CI 0.80-0.98; p = 0.01, I. This meta-analysis shows the superiority of IP chemotherapy over IV infusion in terms of clinical outcomes but toxicity rates. Its precise role in the management of advanced OC remains to be determined.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carcinoma, Ovarian Epithelial; Disease-Free Survival; Female; Humans; Infusions, Intravenous; Infusions, Parenteral; Ovarian Neoplasms; Platinum Compounds; Taxoids; Treatment Outcome

For more than 20 years, the combination of a platinum agent and a taxane has served as the primary chemotherapy strategy for epithelial ovarian cancer. Alternative approaches employing these drugs (intraperitoneal drug delivery, neoadjuvant therapy) have favorably impacted outcomes in selected patient populations. Multiple single agent and combination therapy strategies have been delivered in the second-line (or later) setting with the goal to prolong survival and optimize quality-of-life. The anti-angiogenic agent bevacizumab has been shown to be clinically active when added to chemotherapy and delivered as a "maintenance" strategy in the front-line, platinum-sensitive recurrent and platinum-resistant settings. Several poly-(ADP-ribose) polymerase (PARP) inhibitors are currently utilized as single-agent "second-line" treatment options or in the maintenance setting. Recent clinical research efforts in ovarian cancer have focused on the potential role of checkpoint inhibitors used alone or in combination with PARP inhibitors or anti-angiogenic agents.

Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Bridged-Ring Compounds; Carboplatin; Carcinoma, Ovarian Epithelial; Cisplatin; Drug Delivery Systems; Drug Resistance, Neoplasm; Female; Humans; Neoadjuvant Therapy; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Taxoids

Epithelial ovarian cancer classically presents with vague persistent gastrointestinal, urologic, or nonacute abdominal/pelvic symptoms (bloating, early satiety, discomfort). Ultimately, a pelvic examination or imaging identifies an adnexal mass typically with accompanied advanced peritoneal dissemination. Management involves aggressive cytoreductive surgery in combination with platinum and taxane chemotherapy. Over the last 20 years, optimal resection and mode and timing of chemotherapy have evolved. The authors review the initial diagnosis and management and present the available data and recommendations to guide the decision tree of when to use neoadjuvant, intraperitoneal, HIPEC, dose-dense, and maintenance chemotherapy in the front-line treatment of epithelial ovarian cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carcinoma, Ovarian Epithelial; Combined Modality Therapy; Cytoreduction Surgical Procedures; Female; Humans; Hyperthermia, Induced; Neoadjuvant Therapy; Ovarian Neoplasms; Taxoids

Ovarian cancer is the most lethal gynecologic malignancy. It appears that the vast majority of what seem to be primary epithelial ovarian and primary peritoneal carcinomas is, in fact, secondary from the fimbria, the most distal part of the fallopian tube. Treatment of epithelial ovarian cancer is based on the combination of cytoreductive surgery and combination chemotherapy using taxane and platinum. Although clear cell type is categorized in indolent type, it is known to show relatively strong resistance to carboplatin and paclitaxel regimen and thus poor prognosis compared to serous adenocarcinoma, especially in advanced stages. Irinotecan plus cisplatin therapy may effective for the clear cell adenocarcinoma. The larger expectation for improved prognosis in ovarian carcinoma is related to the use of the new biological agents. One of the most investigated and promising molecular targeted drugs in ovarian cancer is bevacizumab, a monoclonal antibody directed against VEGF. PARP inhibitor is another one. A few recent studies demonstrated positive results of bevacizumab on progression-free survival in ovarian cancer patients, however, investigation of molecular targeting drugs in patients with ovarian cancer are still underway.

Topics: Bridged-Ring Compounds; Carcinoma, Ovarian Epithelial; Combined Modality Therapy; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Humans; Molecular Targeted Therapy; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Peritoneal Neoplasms; Platinum; Prognosis; Taxoids

Suppression of neoangiogenesis and pegylated liposomal doxorubicin (PLD) each contribute to the management of platinum-resistant/refractory ovarian cancer. The aim of this study is to test the combination of bevacizumab and PLD in women with resistant or refractory ovarian cancer.. Eligibility criteria were no more than two prior treatments with platinum-containing regimens and one additional regimen, without anthracyclines. Treatment was administered every 3 weeks (bevacizumab 15 mg/kg beginning on cycle 2 and PLD 30 mg/m(2)). The primary end point was progression-free survival (PFS) at 6 months; the secondary end points included side-effects, overall response rates (ORR) and survival (OS).. Forty-six patients were enrolled. The average number of courses administered was 7. The median PFS was 6.6 months (range 1-24.6 months) according to Gynecologic Cancer Intergroup Committee (GCIC) criteria and 7.8 months (range 2-13.3 months) according to Response Evaluation Criteria in Solid Tumors (RECIST). The median OS was 33.2 months (range 3-37.5+ months). The ORR was 30.2% [95% confidence interval (CI) 17.2-46.1] and the clinical benefit rate (CBR) was 86.1% (95% CI 72.1-94.7). Adverse events included mucosal and dermal erosions (30% grade 3) and asymptomatic cardiac dysfunction. Additional toxic effects included hypertension, headache, renal dysfunction and proteinuria, wound healing delay, and one episode each of central nervous system (CNS) ischemia and hemolytic uremic syndrome.. PLD with bevacizumab has improved activity in recurrent ovarian cancer with increased toxicity.

Topics: Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antibiotics, Antineoplastic; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Bridged-Ring Compounds; Carcinoma, Ovarian Epithelial; Disease-Free Survival; Doxorubicin; Drug Resistance, Neoplasm; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Platinum; Taxoids; Treatment Outcome

Low molecular weight heparin reduces the risk of venous thromboembolism (VTE) and may have antineoplastic effects by interfering with angiogenesis and with tumor growth and metastasis. A multicentre phase II randomized trial was done to evaluate the antineoplastic potential of dalteparin in ovarian cancer (OC).. Women with newly-diagnosed epithelial OC were randomized to receive standard chemotherapy (CT) and one of 3 doses of dalteparin (50 IU/kg, 100 IU/kg, or 150 IU/kg) subcutaneously once daily during the first 3 of 6 cycles of 3-weekly CT. Blood was drawn on day 1 of each cycle for CA125 and, in a substudy of randomized patients, for markers of coagulation activation and angiogenesis. The primary outcome was tumor response defined by ≥ 50% reduction in serum CA125 from baseline sustained for at least 28 days. Patients were followed until the end of CT.. The study was terminated early due to poor recruitment. Seventy-seven women were evaluable for the primary outcome. A 50% drop in CA125 at the end of cycle 3 was seen in 85% of the 50 IU/kg group, 92% of the 100 IU/kg group, and 85% of the 150 IU/kg group. There were no symptomatic VTE or major bleeding events while on dalteparin. Two patients experienced VTE several days after discontinuing study drug. Women on dalteparin had lower levels of D-dimer and thrombin-antithrombin, and higher levels of tissue factor pathway inhibitor, relative to baseline.. Dalteparin is safe and well tolerated in women receiving CT for newly-diagnosed epithelial OC. A dose-response effect was not identified. The lack of control group precluded any inference on the antineoplastic effect of dalteparin.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bridged-Ring Compounds; CA-125 Antigen; Carcinoma, Ovarian Epithelial; Dalteparin; Female; Humans; Membrane Proteins; Middle Aged; Neoplasms, Glandular and Epithelial; Neovascularization, Pathologic; Organoplatinum Compounds; Ovarian Neoplasms; Taxoids

Although chemotherapy is a conventional cancer treatment, it may induce a protumorigenic microenvironment by triggering the release of proinflammatory mediators. In this study, we demonstrate that ovarian tumor cell debris generated by first-line platinum- and taxane-based chemotherapy accelerates tumor progression by stimulating a macrophage-derived "surge" of proinflammatory cytokines and bioactive lipids. Thus, targeting a single inflammatory mediator or pathway is unlikely to prevent therapy-induced tumor progression. Here, we show that combined pharmacological abrogation of the cyclooxygenase-2 (COX-2) and soluble epoxide hydrolase (sEH) pathways prevented the debris-induced surge of both cytokines and lipid mediators by macrophages. In animal models, the dual COX-2/sEH inhibitor PTUPB delayed the onset of debris-stimulated ovarian tumor growth and ascites leading to sustained survival over 120 days postinjection. Therefore, dual inhibition of COX-2/sEH may be an approach to suppress debris-stimulated ovarian tumor growth by preventing the therapy-induced surge of cytokines and lipid mediators.

Topics: Animals; Antineoplastic Agents; Bridged-Ring Compounds; Carcinoma, Ovarian Epithelial; Cell Proliferation; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cytokines; Disease Models, Animal; Disease Progression; Epoxide Hydrolases; Female; Inflammation; Lipids; Macrophages; Mice; Mice, Inbred C57BL; Mice, SCID; Ovarian Neoplasms; Platinum; Signal Transduction; Taxoids

The overall survival (OS) of patients with ovarian cancer is poor while epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer. The aim of the present study was to evaluate the clinico-pathologic characteristics, especially the prognostic factors, for patients with epithelial ovarian cancer (EOC) in Taiwan. Information about newly diagnosed patients with EOC from 2009 to 2012 was retrieved from the database of the Taiwan Cancer Registry. Data from 2009 to 2013 for the respective cases from the claims database of Taiwan's National Health Insurance and National Death Registry were then retrieved. Potential prognostic factors were analyzed. The mean age at diagnosis of the 2,498 patients was 52.8 years. Serous carcinoma and clear cell carcinoma were diagnosed in 43.3% and 22.8% of the total patients, respectively. For patients with early-stage disease, taxane-based adjuvant chemotherapy, stage I, and younger age at diagnosis led to better overall survival (p = 0.030, p = 0.002, p<0.001, respectively) in multivariable analysis. For advanced-stage patients, histology (endometrioid type), taxane-based adjuvant chemotherapy, stage, and age at diagnosis had a significant impact on OS (p<0.001, p = 0.020, p<0.001, p<0.001, respectively). In conclusion, taxane-based chemotherapy impacts the outcome of patients with EOC. Personalized medicine may be needed for different histological types of EOC because of their different outcomes.

Topics: Adenocarcinoma, Clear Cell; Adult; Aged; Antineoplastic Agents; Bridged-Ring Compounds; Carcinoma; Carcinoma, Ovarian Epithelial; Chemotherapy, Adjuvant; Female; Humans; Middle Aged; Multivariate Analysis; Neoplasm Staging; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Prognosis; Registries; Survival Rate; Taxoids; Young Adult

To evaluate the predictive value of genes involved in resistance to platinum-taxane chemotherapy in patients with epithelial ovarian cancer (EOC). Microdissected formalin-fixed tumoral samples from 187 EOC patients' primary tumors (90 and 97 samples from matched patients in the experimental and validation sets, respectively) were analyzed. All specimens were analyzed for ATP7b, BRCA1, BRCA2, PARP1, UIMC1(RAP80), HOXA9, DAXX, TXN (TRX1), THBS1 (TSP1) and PRR13 (TXR1) mRNA expression by quantitative real-time PCR. Most of the patients (172 out of 187) received front-line carboplatin-paclitaxel regimen. Expression levels were correlated with overall (OS) and progression-free (PFS) survival by multivariate analysis. Patients with high TXN and THBS1 expression presented longer PFS (P=0.001 and P<0.001, respectively) and OS (P=0.024 and P<0.001, respectively). High TXR1 expression was associated with decreased PFS (P<0.001) and OS (P<0.001). Multivariate analysis demonstrated that high PRR13/low THBS1 expression was an independent factor for decreased PFS (hazards ratio: 1.94; 95% confidence interval (CI): 1.48-2.92; P=0.008) and OS (hazard ratio: 3.89; 95% CI: 2.16-6.87; P<0.001), whereas low TXN expression was correlated with decreased PFS (hazard ratio: 1.44; 95% CI: 1.05-2.84; P=0.043) and OS (hazard ratio: 2.38; 95% CI: 1.78-2.77; P=0.009). These findings indicate that PRR13/THBS1 and TXN expression could be used for the prediction of resistance to treatment of EOC patients and, therefore, merit to be further evaluated.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carboplatin; Carcinoma, Ovarian Epithelial; Drug Resistance, Neoplasm; Female; Humans; Middle Aged; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Predictive Value of Tests; Prognosis; Repressor Proteins; Taxoids; Thioredoxins; Thrombospondin 1

The aim of this study was to confirm the expression of high mobility group box 1 (HMGB1) in patients with epithelial ovarian cancer (EOC) and to evaluate the prognostic significance of HMGB1.. A total of 74 patients with EOC comprised our cohort. Retrospectively collected tissue microarray from EOC patients treated with debulking surgery followed by taxane and platinum chemotherapy were analyzed for evaluation of the prognostic significance of HMGB1. Expression of HMGB1 was assessed by immunohistochemistry.. The positive staining was detected in 80% of EOC patients and the rate of high HMGB1 expression was 42%. In advanced stage, patients with high HMGB1 expression showed a poorer prognosis than low HMGB1 expression group [median progression-free survival (PFS), 10.8 vs. 21.7 months, P = 0.005]. High HMGB1 expression was an independent predictor for PFS (P = 0.024).. HMGB1 expression is expected as a promising biomarker for EOC and further studies are needed to assess potential roles in EOC.

Topics: Adult; Aged; Antineoplastic Agents; Biomarkers, Tumor; Bridged-Ring Compounds; Carcinoma, Ovarian Epithelial; Cytoreduction Surgical Procedures; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; HMGB1 Protein; Humans; Immunohistochemistry; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Prognosis; Receptor for Advanced Glycation End Products; Retrospective Studies; Survival Rate; Taxoids; Tissue Array Analysis; Treatment Outcome

Individual mutations in the tumor suppressor TP53 alter p53 protein function. Some mutations create a non-functional protein, whereas others confer oncogenic activity, which we term 'oncomorphic'. Since mutations in TP53 occur in nearly all ovarian tumors, the objective of this study was to determine the relationship of oncomorphic TP53 mutations with patient outcomes in advanced serous ovarian cancer patients. Clinical and molecular data from 264 high-grade serous ovarian cancer patients uniformly treated with standard platinum- and taxane-based adjuvant chemotherapy were downloaded from The Cancer Genome Atlas (TCGA) portal. Additionally, patient samples were obtained from the University of Iowa and individual mutations were analyzed in ovarian cancer cell lines. Mutations in the TP53 were annotated and categorized as oncomorphic, loss of function (LOF), or unclassified. Associations between mutation types, chemoresistance, recurrence, and progression-free survival (PFS) were calculated. Oncomorphic TP53 mutations were present in 21.3% of ovarian cancers in the TCGA dataset. Patients with oncomorphic TP53 mutations demonstrated significantly worse PFS, a 60% higher risk of recurrence (HR=1.60, 95% confidence intervals 1.09, 2.33, p=0.015), and higher rates of platinum resistance (χ(2) test p=0.0024) when compared with single nucleotide mutations not categorized as oncomorphic. Furthermore, tumors containing oncomorphic TP53 mutations displayed unique protein expression profiles, and some mutations conferred increased clonogenic capacity in ovarian cancer cell models. Our study reveals that oncomorphic TP53 mutations are associated with worse patient outcome. These data suggest that future studies should take into consideration the functional consequences of TP53 mutations when determining treatment options.

Topics: Adult; Aged; Bridged-Ring Compounds; Carcinoma, Ovarian Epithelial; Cystadenocarcinoma, Serous; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Humans; Middle Aged; Mutation; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Platinum; Prognosis; Taxoids; Tumor Suppressor Protein p53

The aim of the current study was to investigate the role of BRCA1 promoter methylation as predictive factor of response to platinum-taxane-based therapy in sporadic ovarian cancer.. BRCA1 promoter methylation was analyzed in 42 sporadic epithelial ovarian cancers. The results were validated in a second cohort of 137 ovarian cancer patients.. BRCA1 promoter methylation was observed in 35.7 % of patients in the first group and in 33.6 % in the second group. BRCA1 promoter methylation was associated with significant increase in median progression-free survival (PFS) of ovarian cancer patients receiving adjuvant platinum-taxane-based chemotherapy (P = 0.008). Multivariate analysis revealed that BRCA1 promoter methylation remains a favorable factor in regard to PFS (HR 0.52; 95 % CI 0.32-0.85, P = 0.009) after adjustment for other prognostic factors. Under the patients with recurrent disease, BRCA1 promoter methylation was associated with significant longer median PFS of 18.5 months in comparison with 12.8 months PFS for patients without BRCA1 promoter methylation.. BRCA1 promoter methylation is predictive for better response to platinum-taxane-based therapy in EOC.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; BRCA1 Protein; Bridged-Ring Compounds; Carcinoma, Ovarian Epithelial; Disease-Free Survival; Female; Humans; Methylation; Middle Aged; Neoplasms, Glandular and Epithelial; Organoplatinum Compounds; Ovarian Neoplasms; Prognosis; Promoter Regions, Genetic; Taxoids; Young Adult

In epithelial ovarian cancer (EOC), literature on the prognostic value of B-cell lymphoma 2 (Bcl-2) is limited and inconsistent. Little is known about the expression patterns and the prognostic value of prosurvival proteins of the Bcl-2-associated athanogene (BAG) family proteins interacting with Bcl-2. The major aim of this study was to further define the expression pattern and the prognostic role of Bcl-2 together with BAG-1, BAG-3, and BAG-4 proteins in EOC patients receiving platinum/taxane-based chemotherapy. A tissue array was constructed comprising 63 EOC patients. The expression and the prognostic value of Bcl-2, BAG-1, BAG-3, and BAG-4 in EOC were evaluated by immunohistochemistry and multivariate analysis. A positive cytoplasmic staining for Bcl-2 was observed in 23.8% of EOC samples and in all histologic subtypes. BAG-1, BAG-3, and BAG-4 were detected in tumor cell nuclei and cytoplasm. Interestingly, all patients presenting with a positive Bcl-2 staining showed additional positive nuclear and cytoplasmic BAG-4 expression (P=0.014). Expression of Bcl-2, or the BAG family proteins, independent of nuclear or cytoplasmic localization, had no significant impact on either disease-free or overall survival, both in univariate and multivariate survival analyses with the limitation of a small cohort of cases. In this study, no association between Bcl-2 expression in EOC tumor tissue and prognosis was found. Similarly, nuclear and cytoplasmic expression of the prosurvival proteins of the BAG family had no significant impact on patients' outcome.

Topics: Adaptor Proteins, Signal Transducing; Adult; Aged; Antineoplastic Agents; Apoptosis Regulatory Proteins; Bridged-Ring Compounds; Carcinoma, Ovarian Epithelial; DNA-Binding Proteins; Female; Humans; Immunohistochemistry; Middle Aged; Multivariate Analysis; Neoplasm Staging; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Platinum; Prognosis; Proto-Oncogene Proteins c-bcl-2; Survival Analysis; Taxoids; Transcription Factors

To develop a nomogram based on established prognostic factors to predict the probability of 5-year disease-specific mortality after primary surgery for patients with all stages of epithelial ovarian cancer (EOC) and compare the predictive accuracy with the currently used International Federation of Gynecology and Obstetrics (FIGO) staging system.. Using a prospectively kept database, we identified all patients with EOC who had their primary surgery at our institution between January 1996 and December 2004. Disease-specific mortality was estimated using the Kaplan-Meier method. Twenty-eight clinical and pathologic factors were analyzed. Significant factors on univariate analysis were included in the Cox proportional hazards regression model, which identified factors utilized in the nomogram. The concordance index (CI) was used as an accuracy measure, with bootstrapping to correct for optimistic bias. Calibration plots were constructed.. A total of 478 patients with EOC were included. The most predictive nomogram was constructed using seven variables: age, FIGO stage, residual disease status, preoperative albumin level, histology, family history suggestive of hereditary breast/ovarian cancer (HBOC) syndrome, and American Society of Anesthesiologists (ASA) status. This nomogram was internally validated using bootstrapping and shown to have excellent calibration with a bootstrap-corrected CI of 0.714. The CI for FIGO staging alone was significantly less at 0.62 (P=0.002).. We have developed an all-stage nomogram to predict 5-year disease-specific mortality after primary surgery for epithelial ovarian cancer. This tool is more accurate than FIGO staging and should be useful for patient counseling, clinical trial eligibility, postoperative management, and follow-up.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Bridged-Ring Compounds; Carcinoma, Ovarian Epithelial; Chemotherapy, Adjuvant; Female; Humans; Kaplan-Meier Estimate; Middle Aged; Neoplasm Staging; Neoplasms, Glandular and Epithelial; Nomograms; Ovarian Neoplasms; Proportional Hazards Models; Taxoids; Treatment Outcome

The objective of this study was to evaluate the prognostic effect of the apoptosis regulators p53, bax and PUMA for recurrent disease and disease-free survival (DFS) in a series of 105 patients in FIGO-stages I-II with epithelial ovarian cancer, all treated with post-surgical platinum-taxane chemotherapy. For the detection of positivity of the biological markers p53, bax and PUMA the techniques of tissue microarrays and immunohistochemistry (IHC) were used. In tumors the frequency of p53 positivity was 24%, that of bax positivity was 83%, and strong positivity was found for PUMA (43%). The bax status was related to tumor grade (P=0.029). Positive staining for bax was related to strong positivity of PUMA in the tumors (P=0.004). The p53, bax or PUMA status alone or concomitant (p53 bax, p53 PUMA and bax PUMA) were not related to age, histopathological subtype, serous/non-serous tumors or type of the staging procedure at primary surgery. In survival analysis p53-positive tumors (P=0.014) and concomitant p53-positive and weak PUMA-positive tumors (P=0.015) were significantly correlated with shorter DFS. Concomitant p53-negative and bax-positive tumors were significantly correlated with longer survival (P=0.019). FIGO-stage (OR=6.0) and p53 status (OR=4.1) were predictive factors for tumor recurrence in logistic regression analysis and independent prognostic factors (HR=2.4 for both) in multivariate Cox regression analysis. In a separate Cox multivariate regression analysis the p53 bax status (HR=2.2) was an independent prognostic factor for DFS. The p53 PUMA status (HR=0.4) was not an independent prognostic factor, however, a borderline significance (P=0.07) was noted. Our results indicate that FIGO stage and p53 status alone were independent predictive factors for recurrence and prognostic factors for survival. Furthermore, p53 bax status was an independent prognostic factor for survival in this study.

Topics: Adult; Aged; Aged, 80 and over; Apoptosis; Apoptosis Regulatory Proteins; bcl-2-Associated X Protein; Biomarkers, Tumor; Bridged-Ring Compounds; Carcinoma, Ovarian Epithelial; Disease-Free Survival; Female; Follow-Up Studies; Humans; Immunohistochemistry; Middle Aged; Neoplasm Staging; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Proto-Oncogene Proteins; Survival Analysis; Taxoids; Treatment Outcome; Tumor Suppressor Protein p53

We have previously shown that transducin-like enhancer of split 3 (TLE3) is associated with outcome specifically in patients with taxane-treated breast cancer and not in patients treated with anthracycline-based regimens without a taxane. The purpose of this study was to assess the association between TLE3 expression and recurrence in patients with ovarian carcinoma treated with a taxane containing regimen as opposed to those treated with a platinum-based agent alone.. We carried out immunohistochemical staining of TLE3 in two series of ovarian cancer specimens from the University of Alabama at Birmingham, Birmingham, AL and the Royal Hospital for Women, Sydney, Australia. Local and distant recurrences within the first five years of follow-up were analyzed using Kaplan-Meier, Cox proportional hazard, and multivariate analysis to assess an association between TLE3 expression and response to therapy.. TLE3 was expressed in approximately 30% of tumors and expression was associated with a favorable outcome only in patients who had received taxane as part of their treatment regimen (n = 173, HR = 0.62, P = 0.012; P(interaction) = 0.024). Further analysis revealed that the predictive association between TLE3 expression and outcome was strongest in patients with nonserous histology.. High TLE3 expression predicts a favorable response to taxane containing chemotherapy regimens in ovarian carcinoma.. Our findings warrant an independent evaluation of TLE3 as a potential therapeutic response marker for taxane-based chemotherapy in ovarian cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bridged-Ring Compounds; Carcinoma, Ovarian Epithelial; Co-Repressor Proteins; Cohort Studies; Female; Humans; Kaplan-Meier Estimate; Multivariate Analysis; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Proportional Hazards Models; Taxoids; Treatment Outcome

To evaluate the predictive power of serum CA-125 changes in the management of patients undergoing neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) for a new diagnosis of epithelial ovarian carcinoma (EOC).. Using the Cancer Registry databases from our institutions, a retrospective review of patients with FIGO stage IIIC and IV EOC who were treated with platinum-based NACT-IDS between January 2006 and December 2009 was conducted. Demographic data, CA-125 levels, radiographic data, chemotherapy, and surgical-pathologic information were obtained. Continuous variables were evaluated by Student's t test or Wilcoxon-Mann-Whitney test.. One hundred-three patients with stage IIIC or IV EOC met study criteria. Median number of neoadjuvant cycles was 3. Ninety-nine patients (96.1%) were optimally cytoreduced. Forty-seven patients (47.5%) had resection to no residual disease (NRD). The median CA-125 at diagnosis and before interval debulking was 1749U/mL and 161U/mL, respectively. Comparing patients with NRD v. optimal macroscopic disease (OMD), there was no statistical difference in the mean CA-125 at diagnosis (1566U/mL v. 2077U/mL, p=0.1). There was a significant difference in the mean CA-125 prior to interval debulking, 92 v. 233U/mL (p=0.001). In the NRD group, 38 patients (80%) had preoperative CA-125≤100U/mL compared to 33 patients (63.4%) in the OMD group (p=0.04).. Patients who undergo NACT-IDS achieve a high rate of optimal cytoreduction. In our series, after treatment with taxane and platinum-based chemotherapy, patients with a preoperative CA-125 of ≤100U/mL were highly likely to be cytoreduced to no residual disease.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; CA-125 Antigen; Carcinoma, Ovarian Epithelial; Chemotherapy, Adjuvant; Female; Humans; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Neoplasm, Residual; Neoplasms, Glandular and Epithelial; Organoplatinum Compounds; Ovarian Neoplasms; Taxoids

Platinum-resistant and refractory cancers of the ovary, fallopian tube, and peritoneum have a poor prognosis, yet in some cases, they can respond to multiple lines of chemotherapy. Uncertainty remains over optimal drug choice and when therapeutic focus should be switched from active therapy to supportive care.. A retrospective case note review was performed on 274 women treated for platinum-resistant/refractory ovarian, fallopian tube, or peritoneal carcinoma at the Christie Hospital between 2004 and 2008. Baseline data at onset of platinum resistance and outcomes from subsequent lines of therapy were recorded.. A total of 689 lines of therapy were administered with a median overall survival from initiation of first-line therapy for platinum-resistant disease of 61 weeks. Twenty-eight percent of women commenced cytotoxic therapy in the last 3 months of life. Treatment efficacy declined rapidly with successive lines of therapy particularly if disease progression occurred during first-line therapy. Factors independently associated with worse overall survival at recognition of platinum resistance were performance status, presence of stage IV disease, elevated cancer antigen 125, and platinum-refractory disease.. A significant proportion of women who were treated received therapy within the last few months of life with little clinical benefit. Disease progression on 2 consecutive lines of therapy should be used as a guide to discontinue cytotoxic treatment. A subset of patients with poor prognosis at the onset of platinum resistance, who may have little gain from anticancer treatment, can be identified.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; CA-125 Antigen; Carcinoma; Carcinoma, Ovarian Epithelial; Cisplatin; Cytotoxins; Deoxycytidine; Disease-Free Survival; Doxorubicin; Drug Resistance, Neoplasm; Etoposide; Fallopian Tube Neoplasms; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Middle Aged; Neoplasm Recurrence, Local; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Paclitaxel; Peritoneal Neoplasms; Platinum; Polyethylene Glycols; Prognosis; Proportional Hazards Models; Retrospective Studies; Survival Analysis; Taxoids; Treatment Outcome

Despite the fact the standard-of-care primary chemotherapy strategy in epithelial ovarian cancer has undergone very limited changes over the past decade there have been important advances in treatment outcomes resulting from data generated in evidence-based trials that has modified the paradigm for second-line disease management. Recently reported data suggest novel classes of agents, including anti-angiogenic drugs and PARP inhibitors may add to the established utility of standard cytotoxic chemotherapy.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carcinoma, Ovarian Epithelial; Female; Humans; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Platinum; Taxoids

We investigated the relationship between BRCA1 protein expression by immunohistochemistry (IHC) and clinical outcome following platinum and platinum/taxane chemotherapy in sporadic epithelial ovarian cancer (EOC).. BRCA1 IHC was performed on a cohort of 292 ovarian tumours from two UK oncology centres. BRCA1 protein expression levels were correlated with overall survival (OS), progression free survival (PFS) and clinical response to chemotherapy by multivariate analysis.. EOC patients with absent/low BRCA1 protein expression (41%) had a better chance of clinical response following chemotherapy as compared to patients with high BRCA1 expression (odds ratio 2.47: 95%CI 1.10-5.55, p=0.029). Patients with absent/low BRCA1 had a higher probability of clinical response following single agent platinum compared to high BRCA1 expressing patients (68.5% vs. 46.8%), while addition of a taxane increased response rates independent of BRCA1. Overall, patients with absent/low BRCA1 had a better clinical outcome compared to patients with high BRCA1 protein expression in terms of both OS (HR=0.65: 95%CI 0.48-0.88, p=0.006) and PFS (HR=0.74, 95%CI 0.55-0.98, p=0.040).. We confirm that absent/low BRCA1 protein expression is a favourable prognostic marker. However, we also provide the first evidence that absent/low BRCA1 protein expression in sporadic EOC patients predicts for an improved clinical response to chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; BRCA1 Protein; Bridged-Ring Compounds; Carcinoma, Ovarian Epithelial; Cohort Studies; Disease-Free Survival; Female; Gene Expression; Humans; Immunohistochemistry; Middle Aged; Multivariate Analysis; Neoplasms, Glandular and Epithelial; Organoplatinum Compounds; Ovarian Neoplasms; Predictive Value of Tests; Retrospective Studies; Survival Rate; Taxoids