First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)—a gynecologic cancer intergroup study of the NSGO, EORTC GCG and NCIC CTG

Lindemann, Kristina; Christensen, René dePont; Vergote, Ignace; Stuart, Gavin; Izquierdo, Miguel; Kærn, J.; Havsteen, Hanne; Eisenhauer, Elizabeth; Ridderheim, Mona; Lopez, A. B.; Hirte, Hal W.; Aavall-Lundquvist, E; Vrdoljak, Eduard; Green, J; Kristensen, Gunnar B.

doi:10.1093/annonc/mds060

Cited by 28 publications

(23 citation statements)

References 16 publications

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“…According to our NMA SUCRA values, PC produced better outcomes with regard to CR, PD and DCR, while DC was more effective regarding ORR and PC + Epirubicin had a higher efficacy in terms of DCR. These results are consistent with previous studies [26, 37, 38], demonstrating there was no efficacy difference between PC, PC + Epirubicin, and DC. However, some studies indicated that toxicity was lower in PC as compared to PC + Epirubicin [37], PC + Topotecan [38], and DC [26].…”

Section: Discussionsupporting

confidence: 93%

“…These results are consistent with previous studies [26, 37, 38], demonstrating there was no efficacy difference between PC, PC + Epirubicin, and DC. However, some studies indicated that toxicity was lower in PC as compared to PC + Epirubicin [37], PC + Topotecan [38], and DC [26]. Epirubicin inhibits DNA and RNA synthesis by intercalating DNA strands [7] and Topotecan inhibits cancer cell differentiation through PPARγ degradation [12], which disturbs the normal processes of cell division and differentiation, and impedes cell damage repair,.…”

Section: Discussionsupporting

confidence: 93%

“…Pacilitaxel promotes stable microtubule assembly by acting specifically at the beta-tubulin subunit N-terminus [33], impeding depolymerization and inhibiting cancer cell division [9]. In terms of progression-free survival, previous studies showed that PC was more efficacious than GC [23], while no difference was detected when PC was compared to PLD + Carboplatin [20, 34], PC + Topotecan [35], PC + Epirubicin [36, 37] or DC [26]. According to our NMA SUCRA values, PC produced better outcomes with regard to CR, PD and DCR, while DC was more effective regarding ORR and PC + Epirubicin had a higher efficacy in terms of DCR.…”

Section: Discussionmentioning

confidence: 99%

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A network meta-analysis of eight chemotherapy regimens for treatment of advanced ovarian cancer

et al. 2016

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This study compared the short-term efficacies of different chemotherapy regimens in the treatment of advanced ovarian cancer (AOC) through pair-wise and network meta-analyses (NMA). Randomized controlled trials (RCTs) identified in a comprehensive online literature search met our inclusion criteria. Direct and indirect evidence was combined to compare odds ratios (OR) and surfaces under the cumulative ranking curves (SUCRA) across the different treatment regimens. Twelve eligible RCTs were finally included, involving eight regimens (Paclitaxel + Carboplatin [PC], Gemcitabine + Carboplatin [GC], Carboplatin, Pegylated Liposomal Doxorubicin + Carboplatin [PLD + Carboplatin], Paclitaxel, Paclitaxel + Carboplatin + Topotecan [PC + Topotecan], Paclitaxel + Carboplatin + Epirubicin [PC + Epirubicin] and Docetaxel + Carboplatin [DC]). The NMA results revealed that in terms of overall response rate (ORR) and disease control rate (DCR), PC (ORR: OR=2.59, 95%CI=1.20–6.22; DCR: OR=2.58, 95%CI=1.05–6.82) and GC (ORR: OR=2.08, 95%CI=1.08–4.37; DCR: OR=2.43, 95%CI=1.07–5.80) were more effective against AOC than Carboplatin alone. Similarly, PC (OR=0.21, 95%CI=0.05–0.69), GC (OR=0.31, 95%CI=0.09–0.90) and PLD + Carboplatin (OR=0.22, 95%CI=0.04–0.92) slowed disease progression better than Carboplatin alone. We also found that PC was more efficacious against AOC than Carboplatin or Paclitaxel single-agent chemotherapy. Combination chemotherapy is thus recommended for AOC, and should guide subsequent drug development and treatment strategies.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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A network meta-analysis of eight chemotherapy regimens for treatment of advanced ovarian cancer

et al. 2016

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“…In Japan, approximately 7,000 cases of EOC are diagnosed every year, and an estimated 4,467 women died of this disease in 2007 [1]. Despite the use of advanced strategic therapies, including surgery and chemotherapy, the 5-year overall survival (OS) rate is approximately 30% [2,3,4,5]. EOC accounts for approximately 90% of ovarian malignancies, and it is commonly diagnosed at a menopausal age.…”

Section: Introductionmentioning

confidence: 99%

Clinicopathologic features of epithelial ovarian carcinoma in younger vs. older patients: analysis in Japanese women

et al. 2014

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ObjectiveThe purpose of this study was to clarify the clinical features of epithelial ovarian carcinoma (EOC) in younger vs. older patients in Japan.MethodsWe collected data on 1,562 patients with EOC treated at multiple institutions in the Tokai Ovarian Tumor Study Group, and analyzed them retrospectively. All patients were divided into 2 groups: group A (≤40 years old) and group B (>40 years old). The data were analyzed to evaluate prognostic factors and the distribution of features in each group. Patients were subjected to univariate and multivariate analyses to evaluate overall survival (OS).ResultsThe median follow-up time was 45.1 months (range, 1 to 257 months). Patients in group A had a significantly higher rate of stage I disease (67.3% vs. 42.6%, respectively; p<0.001) and the mucinous type (36.7% vs. 13.5%, respectively; p<0.001) than those in group B. There was a significant difference of OS between the 2 groups (p=0.013). However, upon stratification according to the stage, there were no significant differences in the OS between the 2 groups (group A vs. B: stage I, p=0.533; stage II-IV, p=0.407). Multivariate analysis revealed that younger age was not an independent prognostic factor for OS.ConclusionOn the basis of our data, younger patients had a different clinical profile than older patients, particularly regarding the stage of the disease and pathological distribution; however, they showed a similar long-term prognosis, even upon stratification according to the stage.

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“…Nevertheless, although TRAIL is well tolerated in patients, its single-agent efficacy is very limited and not all tumor cell lines respond well (20,21). Paclitaxel has emerged as the first-line therapy for EOC or recurrent EOC, however, its clinical application is usually limited by the dose-dependent toxicity and development of drug resistance (22,23). Therefore, combination chemotherapy is usually required to achieve efficacy at tolerable dosages.…”

Section: Discussionmentioning

confidence: 99%

Smac peptide potentiates TRAIL- or paclitaxel-mediated ovarian cancer cell death in vitro and in vivo

et al. 2012

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Second mitochondria-derived activator of caspases (Smac) is a recently identified protein that is released from mitochondria in response to apoptotic stimuli and promotes apoptosis by antagonizing the inhibitor of apoptosis proteins (IAPs). Our previous study showed that ectopic overexpression of Smac sensitizes drug-resistant tumor cells to TRAIL- or paclitaxel-induced apoptosis in vitro. The present study was designed to explore the effect of the synthesized Smac N7 peptide in a human ovarian cancer cell line and xenograft model. The results showed that the single-agent Smac N7 had a non-cytotoxic effect, but it effectively enhanced TRAIL- or paclitaxel-induced inhibition of cell proliferation in a dose-dependent manner, even in TRAIL-resistant A2780 cells. When Smac N7 was combined with TRAIL or paclitaxel in treating A2780 cell tumor xenografts, synergistic anticancer effects were achieved. Furthermore, the combination therapy caused less damage in normal tissues and more apoptosis in tumor xenografts compared with TRAIL or paclitaxel alone. Increased apoptosis was associated with the downregulation of XIAP, survivin and the increased activity of caspase-3, along with an increased amount of cleaved PARP. In conclusion, this Smac N7 peptide is a promising candidate for ovarian cancer combination therapy, and Smac may be the target for the development of a novel class of anticancer drugs.

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First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)—a gynecologic cancer intergroup study of the NSGO, EORTC GCG and NCIC CTG

Abstract: The addition of epirubicin to standard carboplatin and paclitaxel treatment did not improve survival in patients with advanced ovarian, tubal or peritoneal cancer.

Cited by 28 publications

References 16 publications

A network meta-analysis of eight chemotherapy regimens for treatment of advanced ovarian cancer

A network meta-analysis of eight chemotherapy regimens for treatment of advanced ovarian cancer

Clinicopathologic features of epithelial ovarian carcinoma in younger vs. older patients: analysis in Japanese women

Smac peptide potentiates TRAIL- or paclitaxel-mediated ovarian cancer cell death in vitro and in vivo

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