Chemotherapy versus surgery for initial treatment in advanced ovarian epithelial cancer
ABSTRACT Epithelial ovarian cancer presents at an advanced stage in the majority of women. These women require surgery and chemotherapy for optimal treatment. Conventional treatment is to perform surgery first and then give chemotherapy. However, it is not yet clear whether there are any advantages to using chemotherapy before surgery.
To assess whether there is an advantage to treating women with advanced epithelial ovarian cancer with chemotherapy before cytoreductive surgery (neoadjuvant chemotherapy (NACT)) compared with conventional treatment where chemotherapy follows maximal cytoreductive surgery.
For the original review we searched, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2006), MEDLINE (Silver Platter, from 1966 to 1 Sept 2006), EMBASE via Ovid (from 1980 to 1 Sept 2006), CANCERLIT (from 1966 to 1 Sept 2006), PDQ (search for open and closed trials) and MetaRegister (most current search Sept 2006). For this update randomised controlled trials (RCTs) were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2011) and the Cochrane Gynaecological Cancer Specialised Register (2011), MEDLINE (August week 1, 2011), EMBASE (to week 31, 2011), PDQ (search for open and closed trials) and MetaRegister (August 2011).
RCTs of women with advanced epithelial ovarian cancer (Federation of International Gynaecologists and Obstetricians (FIGO) stage III/IV) who were randomly allocated to treatment groups that compared platinum-based chemotherapy before cytoreductive surgery with platinum-based chemotherapy following cytoreductive surgery.
Data were extracted by two review authors independently, and the quality of included trials was assessed by two review authors independently.
One high-quality RCT met the inclusion criteria. This multicentre trial randomised 718 women with stage IIIc/IV ovarian cancer to NACT followed by interval debulking surgery (IDS) or primary debulking surgery (PDS) followed by chemotherapy. There were no significant differences between the study groups with regard to overall survival (OS) (670 women; HR 0.98; 95% CI 0.82 to 1.18) or progression-free survival (PFS) (670 women; HR 1.01; 95% CI 0.86 to 1.17).Significant differences occurred between the NACT and PDS groups with regard to some surgically related serious adverse effects (SAE grade 3/4) including haemorrhage (12 in NACT group vs 23 in PDS group; RR 0.50; 95% CI 0.25 to 0.99), venous thromboembolism (none in NACT group vs eight in PDS group; RR 0.06; 95% CI 0 to 0.98) and infection (five in NACT group vs 25 in PDS group; RR 0.19; 95% CI 0.07 to 0.50). Quality of life (QoL) was reported to be similar for the NACT and PDS groups.Three ongoing RCTs were also identified.
We consider the use of NACT in women with stage IIIc/IV ovarian cancer to be a reasonable alternative to PDS, particularly in bulky disease. With regard to selecting who will benefit from NACT, treatment should be tailored to the patient and should take into account resectability, age, histology, stage and performance status. These results cannot be generalised to women with stage IIIa and IIIb ovarian cancer; in these women, PDS is the standard. We await the results of three ongoing trials, which may change these conclusions.
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- "e l s e v i e r . c o m / l o c a t e / y g y n o treatment option   . Recently, the findings from several trials reported that patients with stages IIIC/IV EOC randomized to NACT-IDS had the same survival as patients undergoing primary debulking surgery (PDS) followed by chemotherapy and that NACT-IDS was not inferior to PDS   . "
ABSTRACT: TP53 K351N mutation is associated with acquired cisplatin resistance in ovarian cancer cells following exposure to cisplatin. We investigated the effect of TP53 K351N mutation on outcome in patients with epithelial ovarian cancer (EOC) that received platinum-based chemotherapy. We assessed TP53 K351N mutations by allele specific real-time PCR (AS-PCR) and DNA sequencing in tumor samples of 153 patients with stage IIIC/IV EOC. Clinicopathologic and follow-up data were collected by a retrospective chart review. TP53 K351N mutations were detected in 8 (11.27%) of 71 patients underwent neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) but not in 82 patients underwent primary debulking surgery (PDS) (P<0.01). In patients with relapse within 6 months, the relapse rate was 14 (19.72%) of 71 patients for NACT-IDS compared to 15 (18.29%) of 82 patients for PDS (P=0.49), and TP53 K351N mutation was observed in 8 of NACT-IDS 14 patients (57.14% P<0.01). In the patients retreated at first recurrence within 6 months, 7 with TP53 K351N mutation of 14 NACT-IDS patients exhibited progression of disease, compared to 2 of PDS 15 patients (50.00% vs. 13.33%, P=0.04). The median disease-free survival (DFS) for NACT-IDS was 13.0months compared to 15.0months for PDS (P=0.02). In multivariate analysis, TP53 K351N mutation is an independent factor for shorter DFS in the patients underwent NACT-IDS (HR=19.05; P=0.01). TP53 K351N mutation may be associated with induction of platinum resistance after NACT in advanced EOC.Gynecologic Oncology 01/2014; 132(3). DOI:10.1016/j.ygyno.2014.01.028 · 3.77 Impact Factor
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- "However, the result of a meta-analysis of Bristow and Chi  involving 835 patients suggested that NACT, compared with PDS, was associated with a worse OS and it was suggested that the definitive operative intervention should be undertaken as early in the treatment program as possible. But a more recent meta-analysis  of multiply central randomized trials concluded that survival was similar in patients treated with NACT followed by interval debulking surgery compared to primary debulking followed by chemotherapy and criticized the meta-analysis of Bristow and Chi . "
ABSTRACT: The purpose of the current study is to analyze the existing data comparing neoadjuvant chemotherapy with primary debulking surgery (PDS) in patients with advanced ovarian carcinoma. Patients with stage IIIC and IV ovarian cancer were identified from articles in Medline, PubMed, Cochrane Library, and EMBASE database (1989 to February 2013). Two authors independently extracted the data. To assess the risk of bias of included literatures, Cochrane Collaboration's risk of bias tool was used. Meta-analysis on literatures was conducted by using RevMan 5.2 software. Two high-quality randomized controlled trials (RCTs) met the inclusion criteria. These multicenter trials randomized 1,220 women with stage IIIc/IV ovarian cancer to NACT or PDS followed by chemotherapy. There were no significant differences between the study groups with regard to overall survival (OS) (1,120 women; HR 0.98; 95% CI 0.85 to 1.14) or progression-free survival (PFS) (1,120 women; HR 1.03; 95% CI 0.91 to 1.16). There was no statistical difference in median OS and PFS between the two treatment groups. With regard to selecting who will benefit from NACT, treatment should be tailored to the patient and should take into account respectability, age, histology, stage, and performance status.World Journal of Surgical Oncology 10/2013; 11(1):267. DOI:10.1186/1477-7819-11-267 · 1.41 Impact Factor
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ABSTRACT: Ovarian cancer has a poor prognosis and advanced ovarian cancer lacks effective therapy. In this study, we seek to establish targeting therapy for ovarian cancer through tumor tissue-specific delivery of miRNA-29b to reexpress PTEN tumor-suppressor gene. A chimera (Chi-29b) was constructed to compose of a mucin 1 (MUC1) aptamer targeting tumor cell surface MUC1 protein and miR-29b inhibiting DNA methyltransferases' expression, subsequently reexpressing PTEN gene. The specificity and efficacy of the chimera delivery were analyzed in OVCAR-3 ovarian tumor cells, and the biological activities of the chimera were identified by the expression of its downstream molecules and cell apoptosis. We demonstrated that Chi-29b chimera can be specifically delivered into OVCAR-3 cells in a concentration-dependent manner. Dicer efficiently cleaved the Chi-29b chimera to release miR-29b. Chi-29b chimera downregulated Dnmt1, Dnmt3a, and Dnmt3b protein levels; induced hypomethylation in PTEN promoter; and upregulated PTEN mRNA and protein expression in OVCAR-3 cells. Importantly, Chi-29b chimera significantly induced apoptosis in OVCAR-3 cells. Our study indicated that Chi-29b chimera can effectively exert antitumor effect through specific delivery of miR-29b into OVCAR-3 tumor cells, subsequently reexpressing PTEN gene and inducing cell apoptosis.Targeted Oncology 11/2012; 7(4). DOI:10.1007/s11523-012-0236-7 · 4.00 Impact Factor