scholarly journals A Randomized Phase 3 Clinical Trial of the Combination of Plinabulin (plin) + Pegfilgrastim (peg) Versus (vs) Peg Alone for Tac (docetaxel, doxorubicin, cyclophosphamide) Induced Neutropenia (cin)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3590-3590
Author(s):  
Douglas W. Blayney ◽  
Lan Huang ◽  
Ramon Mohanlal
Keyword(s):  
Phase Ii ◽  
Bone Pain ◽  
Phase 3 ◽  
Anticancer Effects ◽  
Validated Questionnaire ◽  
Chemotherapy Dose ◽  
Treated Breast ◽  
Dose Modifications ◽  
Confirmatory Phase ◽  
Treated Breast Cancer

Trial in Progress: Granulocyte colony stimulating factors (G-CSFs) (including Peg) reduce, but do not completely ameliorate CIN. Plinabulin is a novel, small molecule, single-dose-per cycle therapy, with equal activity against docetaxel CIN vs. Peg, but with several advantages: Plin has 1. Less bone pain, 2. Anticancer effects, and 3. Dosing 30 min after chemotherapy (chemo). The CIN nadir with Plin occurs in week 2 and with Peg in week 1 of the chemo cycle. All these features suggest a mechanism of action (MoA) with Plin that is different from Peg (Blayney, ASCO 2018; IASLC 2018). Neutrophil demargination with Plin and a reduced neutrophil transit time consistent with IL-6 signaling, and reversal of a LSK block in bone marrow, suggest protective rather than a stimulatory MoA for Plin in CIN (Blayney, SLB 2018; Ghosh, AACR 2018, Suwa, Am J Physiol 2000). Due to their differences in MoA, there is a strong rationale to combine Plin and Peg, as this offers the potential of better protection against CIN in both week 1 and 2 in the chemo cycle. In the Phase II portion of study BPI2358-106 (Study 106., NCT03294577), we evaluated the effects of the Plin combined with Peg on CIN and Bone Pain. Study 106 treated breast cancer (BC) patients with TAC with 6 mg Peg alone (Peg6), or Peg6+Plin. Plin dose was 20 mg/m2. Grade (Gr) 3 and 4 neutropenia frequency, duration of Gr 3 and 4 neutropenia (DSMN), and neutrophil nadir was based on absolute neutrophil counts, obtained on days 0, 1, 3, 6, 7, 8, 9, 10, 11, 12, 13, 15. Bone pain was assessed by a validated questionnaire on days 1, 2, 3, 4, 6, 7, 8, 9, and expressed as % of patients reporting bone pain. Phase II Results. The confirmatory phase 3 portion of study 106 will test addition of Plin to Peg6, which may offer superior protection against TAC CIN vs Peg alone without bone pain. The Plin/Peg combination is a novel CIN approach with the potential to optimize chemotherapy, by minimizing chemotherapy dose modifications due to CIN or bone pain.*p<0.05; **p<0.001; ***P<0.01 Peg+Plin vs Peg 6mg Table Disclosures Blayney: BeyondSpring Pharmaceuticals: Research Funding. Huang:BeyondSpring Pharmaceuticals: Employment. Mohanlal:BeyondSpring Pharmaceuticals: Employment.

Gemcitabine and capecitabine in combination for advanced anthracycline and taxane pre-treated breast cancer patients: A phase II study

2009 ◽  
Vol 49 (1) ◽  
pp. 35-41 ◽  
Author(s):  
Annika Malmström ◽  
Jörgen Hansen ◽  
Lena Malmberg ◽  
Lena Carlsson ◽  
Jan-Henry Svensson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Breast Cancer Patients ◽  
Treated Breast ◽  
Treated Breast Cancer

Endometrial Carcinoma in Tamoxifen-Treated Breast Cancer Patients

1991 ◽  
Vol 3 (4) ◽  
pp. 267-270 ◽  
Author(s):  
G. Spinelli ◽  
N. Bardazzi ◽  
A. Citernesi ◽  
M. Fontanarosa ◽  
P. Curiel
Keyword(s):  
Breast Cancer ◽  
Endometrial Carcinoma ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Treated Breast ◽  
Treated Breast Cancer

Beneficial effects of the redox-active complex Cu[15]pyN5 in doxorubicin-treated breast cancer cells

2012 ◽  
Vol 53 ◽  
pp. S119-S120
Author(s):  
A.S. Fernandes⁎ ◽  
M. Cipriano ◽  
J. Costa ◽  
M.F. Cabral ◽  
J. Miranda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Active Complex ◽  
Beneficial Effects ◽  
Redox Active ◽  
Treated Breast ◽  
Treated Breast Cancer

scholarly journals MiR-9-3p regulates the biological functions and drug resistance of gemcitabine-treated breast cancer cells and affects tumor growth through targeting MTDH

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Yike Wang ◽  
Lifeng Dong ◽  
Fang Wan ◽  
Fangfang Chen ◽  
Dianlei Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Biological Functions ◽  
Qrt Pcr ◽  
Treated Breast ◽  
Cancer Tissues ◽  
Treated Breast Cancer

AbstractThis study explored the role of MTDH in regulating the sensitivity of breast cancer cell lines to gemcitabine (Gem) and the potential miRNAs targeting MTDH. The expression of MTDH in cancer tissues and cells was detected by immunohistochemical staining or qRT-PCR. The target genes for MTDH were predicted by bioinformatics and further confirmed by dual-luciferase reporter assay and qRT-PCR. Cancer cells were transfected with siMTDH, MTDH, miR-9-3p inhibitor, or mimics and treated by Gem, then CCK-8, colony formation assay, tube formation assay, flow cytometry, wound healing assay, and Transwell were performed to explore the effects of MTDH, miR-9-3p, and Gem on cancer cell growth, apoptosis, migration, and invasion. Expressions of VEGF, p53, cleaved caspase-3, MMP-2, MMP-9, E-Cadherin, N-Cadherin, and Vimentin were determined by Western blot. MTDH was high-expressed in cancer tissues and cells, and the cells with high-expressed MTDH were less sensitive to Gem, while silencing MTDH expression significantly promoted the effect of Gem on inducing apoptosis, inhibiting cell migration, invasion, and growth, and on regulating protein expressions of cancer cells. Moreover, miR-9-3p had a targeted binding relationship with MTDH, and overexpressed miR-9-3p greatly promoted the toxic effects of Gem on cancer cells and expressions of apoptosis-related proteins, whereas overexpressed MTDH partially reversed such effects of overexpressed miR-9-3p. The study proved that miR-9-3p regulates biological functions, drug resistance, and the growth of Gem-treated breast cancer cells through targeting MTDH.

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