Efficacy and safety of docetaxel (Taxotere™) in heavily pretreated advanced breast cancer patients

Bonneterre, Jacques; Spielman, M.; Guastalla, Jean‐Paul; Marty, M.; Viens, Patrice; Chollet, Philippe; Roché, Henri; Fumoleau, P.; Mauriac, L.; Bourgeois, H.; Namer, M.; Bergerat, J. P.; Misset, Jean-Louis; Trandafir, L.; Mahjoubi, M.

doi:10.1016/s0959-8049(99)00174-4

Cited by 48 publications

(26 citation statements)

References 20 publications

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“…10 Therefore, it is essential to identify predictive markers for chemotherapy selection, and to better understand mechanisms of taxane-induced cell death for rational development of novel targeted and combinatorial treatment to occur. We previously demonstrated that cells with low levels of Daxx have reduced sensitivity to taxanes 20,21 by persisting in a prometaphase block, escaping taxane-induced cell death.…”

Section: Discussionmentioning

confidence: 99%

“…10 Predicting and overcoming resistance to these agents would represent a major improvement in the clinical management of breast cancer. 11 Besides alteration in the expression of tubulin or microtubuleassociated proteins and multidrug resistance, dysregulation of cellular pathways such as cell cycle control, cell proliferation, apoptosis and nuclear-cytoplasmic transport have been linked to taxane activity and resistance.…”

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confidence: 99%

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USP7 and Daxx regulate mitosis progression and taxane sensitivity by affecting stability of Aurora-A kinase

et al. 2013

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A large number of patients are resistant to taxane-based chemotherapy. Functional mitotic checkpoints are essential for taxane sensitivity. Thus, mitotic regulators are potential markers for therapy response and could be targeted for anticancer therapy. In this study, we identified a novel function of ubiquitin (Ub)-specific processing protease-7 (USP7) that interacts and cooperates with protein death domain-associated protein (Daxx) in the regulation of mitosis and taxane resistance. Depletion of USP7 impairs mitotic progression, stabilizes cyclin B and reduces stability of the mitotic E3 Ub ligase, checkpoint with forkhead and Ring-finger (CHFR). Consequently, cells with depleted USP7 accumulate Aurora-A kinase, a CHFR substrate, thus elevating multipolar mitoses. We further show that these effects are independent of the USP7 substrate p53. Thus, USP7 and Daxx are necessary to regulate proper execution of mitosis, partially via regulation of CHFR and Aurora-A kinase stability. Results from colony formation assay, in silico analysis across the NCI60 platform and in breast cancer patients suggest that USP7 levels inversely correlate with response to taxanes, pointing at the USP7 protein as a potential predictive factor for taxane response in cancer patients. In addition, we demonstrated that inhibition of Aurora-A attenuates USP7-mediated taxane resistance, suggesting that combinatorial drug regimens of Taxol and Aurora-A inhibitors may improve the outcome of chemotherapy response in cancer patients resistant to taxane treatment. Finally, our study offers novel insights on USP7 inhibition as cancer therapy.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

USP7 and Daxx regulate mitosis progression and taxane sensitivity by affecting stability of Aurora-A kinase

et al. 2013

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“…[12][13][14] Indeed, up to 50% of cancer patients are resistant or become PAPer tyPe rePOrt resistant to PTX during drug administration. [15][16][17] Therefore, it is compelling to overcome taxane resistance or to find alternative therapeutic strategies that would kill tumor cells more efficiently than taxanes. Over the past decades great translational effort has been directed toward the development of drugs that target the mitotic spindle assembly or function (such as Eg5, Aurora, Plk1, or cyclin-dependent kinases).…”

Section: Introductionmentioning

confidence: 99%

Targeting mitotic exit with hyperthermia or APC/C inhibition to increase paclitaxel efficacy

et al. 2013

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Microtubule-poisoning drugs, such as Paclitaxel (or taxol, PtX), are powerful and commonly used anti-neoplastic agents for the treatment of several malignancies. PtX triggers cell death, mainly through a mitotic arrest following the activation of the spindle assembly checkpoint (SAC). Cells treated with PtX slowly slip from this mitotic block and die by mitotic catastrophe. However, cancer cells can acquire or are intrinsically resistant to this drug, posing one of the main obstacles for PtX clinical effectiveness. In order to override PtX resistance and increase its efficacy, we investigated both the enhancement of mitotic slippage and the block of mitotic exit.to test these opposing strategies, we used physiological hyperthermia (Ht) to force exit from PtX-induced mitotic block and the anaphase-promoting complex/cyclosome (APC/C) inhibitor, protAMe, to block mitotic exit. We observed that application of Ht on PtX-treated cells forced mitotic slippage, as shown by the rapid decline of cyclin B levels and by microscopy analysis. Similarly, Ht induced mitotic exit in cells blocked in mitosis by other antimitotic drugs, such as Nocodazole and the Aurora A inhibitor MLN8054, indicating a common effect of Ht on mitotic cells. On the other hand, protAMe prevented mitotic exit of PtX and MLN8054 arrested cells, prolonged mitosis, and induced apoptosis. In addition, we showed that protAMe prevented Ht-mediated mitotic exit, indicating that stress-induced APC/C activation is necessary for Ht-induced mitotic slippage.Finally, Ht significantly increased PtX cytotoxicity, regardless of cancer cells' sensitivity to PtX, and this activity was superior to the combination of PtX with pro-tAMe. Our data suggested that forced mitotic exit of cells arrested in mitosis by anti-mitotic drugs, such as PtX, can be a more successful anticancer strategy than blocking mitotic exit by inactivation of the APC/C.

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“…The use of Mphase inhibitors such as taxanes and vinorelbine in these patients is widely accepted. Response rates of 22 to 28% are reported for paclitaxel (Perez, 1998), 29 to 41% for docetaxel (Bonneterre et al, 1999;Trudeau, 1999) and 15 to 16% for vinorelbine in this setting (Degardin et al, 1994;Ibrahim et al, 1999). The duration of remission is approximately 4 to 5 months (Degardin et al, 1994;Ibrahim et al, 1999).…”

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confidence: 98%

Randomised, phase II trial comparing oral capecitabine (Xeloda®) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines

et al. 2002

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Capecitabine, an oral fluoropyrimidine carbamate, was designed to generate 5-fluorouracil preferentially at the tumour site. This randomised, phase II trial evaluated the efficacy and safety of capecitabine or paclitaxel in patients with anthracyclinepretreated metastatic breast cancer. Outpatients with locally advanced and/or metastatic breast cancer whose disease was unresponsive or resistant to anthracycline therapy were randomised to 3-week cycles of intermittent oral capecitabine (1255 mg m 72 twice daily, days 1 -14, (22 patients)) or a reference arm of i.v. paclitaxel (175 mg m 72 , (20 patients)). Two additional patients were initially randomised to continuous capecitabine 666 mg m 72 twice daily, but this arm was closed following selection of the intermittent schedule for further development. Overall response rate was 36% (95% CI 17 -59%) with capecitabine (including three complete responses) and 26% (95% CI 9 -51%) with paclitaxel (no complete responses). Median time to disease progression was similar in the two treatment groups (3.0 months with capecitabine, 3.1 months with paclitaxel), as was overall survival (7.6 and 9.4 months, respectively). Paclitaxel was associated with more alopecia, peripheral neuropathy, myalgia and neutropenia, whereas typical capecitabine-related adverse events were diarrhoea, vomiting and hand -foot syndrome. Twenty-three per cent of capecitabine-treated patients and 16% of paclitaxel-treated patients achieved a 510% improvement in Karnofsky Performance Status. Oral capecitabine is active in anthracycline-pretreated advanced/ metastatic breast cancer and has a favourable safety profile. Furthermore, capecitabine provides a convenient, patientorientated therapy.

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Efficacy and safety of docetaxel (Taxotere™) in heavily pretreated advanced breast cancer patients

Cited by 48 publications

References 20 publications

USP7 and Daxx regulate mitosis progression and taxane sensitivity by affecting stability of Aurora-A kinase

USP7 and Daxx regulate mitosis progression and taxane sensitivity by affecting stability of Aurora-A kinase

Targeting mitotic exit with hyperthermia or APC/C inhibition to increase paclitaxel efficacy

Randomised, phase II trial comparing oral capecitabine (Xeloda®) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines

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