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A Pilot Study of Extended Adjuvant Therapy with Metronomic Docetaxel for Patients with Operable Triple-Negative Breast Cancer.

ABSTRACT: BACKGROUND:Triple-negative breast(TNBC) cancer is a molecular subtype of breast cancer with poor prognosis and did not get approved targeted therapy till now. In the last years, metronomic chemotherapy (mCTH) was investigated to improve treatment outcomes in TNBC patients both in early and metastatic setting due to its anti-angiogenic and immune-stimulatory mechanisms. The aim of this study is to evaluate the efficacy and safety of extended adjuvant chemotherapy with metronomic docetaxel for patients with operable TNBC. METHODS:31 women with clinically and pathologically proved operable TNBC, either node-negative or node-positive with tumor size ? 0,5 cm were enrolled after finishing the primary standard of care treatment. The patients were subjected to extended adjuvant therapy for 6 months with metronomic low dose docetaxel with starting dose of 15mg/m2 in weekly bases for 4 weeks then the dose was escalated to 20 mg/m2 once per week if there were no side effects. RESULTS:After a median follow up of 36 months (range 6-52), 24 patients (77.4%) were still alive. During the period of follow-up, 12 patients (38.7%) showed disease relapse and 19(61.3%) cases remain free of the disease. The estimated mean of DFS in our study was 38.26 months (95%CI; 31.87 - 44.65) with 2 and 3 years DFS rate of 70.5 % and 56.4% respectively while the estimated mean of OS was 43.75 months (95% CI; 38.35 - 49.16) with 2 and 3 years OS rates 83.3% and 78.1% respectively, Generally the treatment was tolerated with mild to moderate hematological and non hematological adverse events, all are grade 1,2 and treatment-related deaths were not observed. CONCLUSION:Extended adjuvant treatment for 6 months with metronomic docetaxel after the primary standard of care therapy was tolerated and has an encouraging survival benefit in patients with operable TNBC and these results need further evaluation in randomized control studies.
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SUBMITTER: Abdelmaksoud BA

PROVIDER: S-EPMC7437317 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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A Pilot Study of Extended Adjuvant Therapy with Metronomic Docetaxel for Patients with Operable Triple-Negative Breast Cancer.

Abdelmaksoud Bader A BA Mohammed Abdelmotaleb A Toam Mostafa M MM

Asian Pacific journal of cancer prevention : APJCP 20200301 3

<h4>Background</h4>Triple-negative breast(TNBC) cancer is a molecular subtype of breast cancer with poor prognosis and did not get approved targeted therapy till now. In the last years, metronomic chemotherapy (mCTH) was investigated to improve treatment outcomes in TNBC patients both in early and metastatic setting due to its anti-angiogenic and immune-stimulatory mechanisms. The aim of this study is to evaluate the efficacy and safety of extended adjuvant chemotherapy with metronomic docetaxel ...[more]

PMID: 32212803

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Project description:BackgroundPatients diagnosed with triple negative breast cancer (TNBC) have limited treatment options and often suffer from resistance and toxicity due to chemotherapy. We previously found that depleting calcium and integrin-binding protein 1 (CIB1) induces cell death selectively in TNBC cells, while sparing normal cells. Therefore, we asked whether CIB1 depletion further enhances tumor-specific killing when combined with either the commonly used chemotherapeutic, docetaxel, or the cell death-inducing ligand, TRAIL.MethodsWe targeted CIB1 by RNA interference in MDA-MB-436, MDA-MB-231, MDA-MB-468, docetaxel-resistant MDA-MB-436 TNBC cells and ME16C normal breast epithelial cells alone or combination with docetaxel or TRAIL. Cell death was quantified via trypan blue exclusion using flow cytometry and cell death mechanisms were analyzed by Western blotting. Cell surface levels of TRAIL receptors were measured by flow cytometry analysis.ResultsCIB1 depletion combined with docetaxel significantly enhanced tumor-specific cell death relative to each treatment alone. The enhanced cell death strongly correlated with caspase-8 activation, a hallmark of death receptor-mediated apoptosis. The death receptor TRAIL-R2 was upregulated in response to CIB1 depletion, which sensitized TNBC cells to the ligand TRAIL, resulting in a synergistic increase in cell death. In addition to death receptor-mediated apoptosis, both combination treatments activated a non-apoptotic mechanism, called paraptosis. Interestingly, these combination treatments also induced nearly complete death of docetaxel-resistant MDA-MB-436 cells, again via apoptosis and paraptosis. In contrast, neither combination treatment induced cell death in normal ME16C cells.ConclusionNovel combinations of CIB1 depletion with docetaxel or TRAIL selectively enhance naive and docetaxel-resistant TNBC cell death while sparing normal cell. Therefore, combination therapies that target CIB1 could prove to be a safe and durable strategy for treatment of TNBC and potentially other cancers.

Dataset Information

A Pilot Study of Extended Adjuvant Therapy with Metronomic Docetaxel for Patients with Operable Triple-Negative Breast Cancer.

Publications

A Pilot Study of Extended Adjuvant Therapy with Metronomic Docetaxel for Patients with Operable Triple-Negative Breast Cancer.

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