Phase III Randomized Trial of Docetaxel-Carboplatin Versus Paclitaxel-Carboplatin as First-line Chemotherapy for Ovarian Carcinoma

Vasey, P.; Jayson, Gordon C; Gordon, Alan N.; Gabra, Hani; Coleman, Robert E.; Atkinson, R; Parkin, David E.; Paul, James; Hay, A.; Kaye, Stan B.

doi:10.1093/jnci/djh323

Cited by 555 publications

(324 citation statements)

References 25 publications

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“…Ranges were selected from the results of 3-day cytotoxicity assays on parental cell lines (Table S3) For carboplatin and taxol a dose range of up to 20µg/ml and 120ng/ml respectively was deemed clinically relevant following pharmacokinetic studies for a dose of carboplatin at AUC 5 and taxol at 175mg/m 2 which are often administered to patients in clinical trials as single agents (du Bois et al 1997;Go et al 1999;ICON3 2002;Joerger et al 2006;Markman et al 2010;Mross et al 2000;Oguri et al 1988;Ozols et al 2003;Pfisterer et al 2006;Rowinsky 1997;Vasey et al 2004). …”

Section: Dose Optimisationmentioning

confidence: 99%

Carboplatin and taxol resistance develops more rapidly in functional BRCA1 compared to dysfunctional BRCA1 ovarian cancer cells

Busschots

O’Toole

O’Leary

et al. 2015

Experimental Cell Research

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Section: Dose Optimisationmentioning

confidence: 99%

Carboplatin and taxol resistance develops more rapidly in functional BRCA1 compared to dysfunctional BRCA1 ovarian cancer cells

Busschots

O’Toole

O’Leary

et al. 2015

Experimental Cell Research

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“…In Japan, ovarian cancer is the eighth leading cause of death from cancer in woman, but a steady upward trend has become evident in recent years. Ovarian clear cell carcinoma (OCCC) has a higher incidence in Japan at 24.7% of all epithelial ovarian cancers (1), than in North America and Europe (1-12%) (2)(3)(4)(5). OCCC has clinical characteristics and pathologic significance based on molecular features that are distinct from high-grade serous carcinoma of the ovary (6).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia promotes glycogen synthesis and accumulation in human ovarian clear cell carcinoma

et al. 2012

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Abstract. Ovarian clear cell carcinoma (OCCC) has several significant characteristics based on molecular features that are distinct from those of ovarian high-grade serous carcinoma. Cellular glycogen accumulation is the most conspicuous feature of OCCC and in the present study its metabolic mechanism was investigated. The amount of glycogen in cells cultured under hypoxia increased significantly and approximately doubled after 48 h (P<0.01) compared to that under normoxic conditions. Periodic acid-Schiff positive staining also demonstrated intracellular glycogen storage. Western blot analysis revealed that HIF1α, which was overexpressed and stabilized under hypoxic conditions, led to an increase in the levels of cellular glycogen synthase 1, muscle type (GYS1), and conversely to a decrease in inactive phosphorylated GYS1 at serine (Ser) 641. Additional increases were observed in both protein phosphatase 1, which dephosphorylates and thereby induces GYS1 enzyme activity, and glycogen synthase kinase 3 beta (GSK3β) phosphorylated at Ser9, which is inactive on phosphorylation of GYS1 and subsequently induces its enzyme activity. By contrast, the level of PYGM-b decreased. These results indicated that the glycogen accumulation under a hypoxic environment resulted in the promotion of glycogen synthesis, but did not lead to inhibition of glycogen degradation and/or consumption. Under hypoxic conditions, HAC2 cells showed activation of the PI3K/AKT pathway caused by a mutation in exon 20 of PIK3CA, encoding the catalytic subunit p110α of PI3K. The resulting activation of AKT (phosphoSer473) also plays a role as a central enhancer in glycogen synthesis through suppression of GSK3β via phosphorylation at Ser9. Hypoxia decreased the cytocidal activity of cisplatin and doxorubicin to various degrees. In conclusion, the hypoxic conditions together with HIF1 expression and stabilization increased the intracellular glycogen contents and resistance to the anticancer drugs.

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“…There is a large interindividual variability in toxicity and therapeutic effect of paclitaxel in ovarian cancer treatment, which remains a clinically relevant problem with implications on survival and quality of life of the patients and practical with regard to the handling of dose delay, dose reduction or cessation of the treatment. 2 Several possible causes of this variability have been suggested; especially the notion that single-nucleotide polymorphisms (SNPs) in certain genes could cause significant changes in the affinity and/or expression of key transporters or metabolizing enzymes. Paclitaxel is metabolized to inactive compounds by CYP2C8 and CYP3A4 in the liver, [3][4][5] and is also a substrate for the adenosine triphosphate-driven efflux pump P-glycoprotein encoded by the ABCB1 gene.…”

Section: Introductionmentioning

confidence: 99%

Impact of CYP2C8*3 on paclitaxel clearance: a population pharmacokinetic and pharmacogenomic study in 93 patients with ovarian cancer

et al. 2010

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The primary purpose of this study was to evaluate the effect of CYP2C8*3 and three genetic ABCB1 variants on the elimination of paclitaxel. We studied 93 Caucasian women with ovarian cancer treated with paclitaxel and carboplatin. Using sparse sampling and nonlinear mixed effects modeling, the individual clearance of unbound paclitaxel was estimated from total plasma paclitaxel and Cremophor EL. The geometric mean of clearance was 385 l h -1 (range 176-726 l h -1 ). Carriers of CYP2C8*3 had 11% lower clearance than non-carriers, P ¼ 0.03. This has not been shown before in similar studies; the explanation is probably the advantage of using both unbound paclitaxel clearance and a population of patients of same gender. No significant association was found for the ABCB1 variants C1236T, G2677T/A and C3435T. Secondarily, other candidate single-nucleotide polymorphisms were explored with possible associations found for CYP2C8*4 (P ¼ 0.04) and ABCC1 g.7356253C4G (P ¼ 0.04).

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Phase III Randomized Trial of Docetaxel-Carboplatin Versus Paclitaxel-Carboplatin as First-line Chemotherapy for Ovarian Carcinoma

Cited by 555 publications

References 25 publications

Carboplatin and taxol resistance develops more rapidly in functional BRCA1 compared to dysfunctional BRCA1 ovarian cancer cells

Carboplatin and taxol resistance develops more rapidly in functional BRCA1 compared to dysfunctional BRCA1 ovarian cancer cells

Hypoxia promotes glycogen synthesis and accumulation in human ovarian clear cell carcinoma

Impact of CYP2C8*3 on paclitaxel clearance: a population pharmacokinetic and pharmacogenomic study in 93 patients with ovarian cancer

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