Objective:Endocrine therapy with fulvestrant has shown synergistic antitumor effects with some chemotherapy drugs in vitro.This study evaluated the efficacy and safety of fulvestrant with vinorelbine in patients with ...Objective:Endocrine therapy with fulvestrant has shown synergistic antitumor effects with some chemotherapy drugs in vitro.This study evaluated the efficacy and safety of fulvestrant with vinorelbine in patients with hormone receptor positive(HR+)/human epidermal growth factor receptor-2-negative(HER2−)recurrent or metastatic breast cancer.Methods:Patients were intramuscularly administered fulvestrant 500 mg(day 1 per cycle for 28 days)and oral vinorelbine(60 mg/m2 on days 1,8,and 15 of each cycle).The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival,objective response rate,disease control rate,duration of response,and safety.Results:A total of 38 patients with HR+/HER2−advanced breast cancer included in the study were followed up for a median time of 25.1 months.The overall median PFS was 9.86 months[95%confidence interval(CI)7.2-23.13],and the median PFS of the first-line and the second-line treatment population was 20.73 months(95%CI 9.82 to NR)and 4.27 months(95%CI 3.68 to NR),respectively.Most adverse events reported were of grade 1/2,and none were of grade 4/5.Conclusions:This is the first exploratory study of a fulvestrant and oral vinorelbine regimen in the treatment of HR+/HER2−recurrent and metastatic breast cancer.The combination chemo-endocrine therapy was efficacious,safe,and promising for patients with HR+/HER2−advanced breast cancer.展开更多
For the quantitative determination of Fulvestrant, Benzyl alcohol, and Benzyl benzoate in Fulvestrant injection, an original RP-HPLC approach was developed. The gradient method was developed using HPLC and a Phenomene...For the quantitative determination of Fulvestrant, Benzyl alcohol, and Benzyl benzoate in Fulvestrant injection, an original RP-HPLC approach was developed. The gradient method was developed using HPLC and a Phenomenex Luna C8, 150 × 4.6 mm, i.d 3.0 μm particle size column with a gradient programme of mobile phases A and B. With a flow rate of 1.5 mL/minute, injection volume of 10 μL, and column temperature of 35°C, UV wavelength detection at 254 nm for Benzyl alcohol and Benzoyl Benzoate and 280 nm for Fulvestrant, mobile phase-A consists of DI water and mobile phase-B consists of Acetonitrile. The current study describes a single HPLC method for developing a Fulvestrant (Active), Benzyl alcohol (Cosolvent), and Benzyl Benzoate (Cosolvent) assay for Fulvestrant injection. The assay method was determined to be suitable for quantifying three components in the pharmaceutical product and was verified according to ICH guidelines.展开更多
The 88 kDa glycoprotein known as GP88, Progranulin or PC cell derived growth factor is an autocrine growth factor with a unique cysteine rich motif that is over expressed in breast cancer whereas it is negative in nor...The 88 kDa glycoprotein known as GP88, Progranulin or PC cell derived growth factor is an autocrine growth factor with a unique cysteine rich motif that is over expressed in breast cancer whereas it is negative in normal mammary epithelial cells. It has been shown to play a major role in estrogen independence, tamoxifen resistance and tumorigenesis of breast cancer cells. In the present study, we investigated the effect of GP88 overexpression on the response of the human breast cancer MCF-7 cells to the pure estrogen receptor antagonist fulvestrant (ICI 182,780). While fulvestrant effectively inhibited cell proliferation of empty vector transfected cells, it had no inhibitory effect on the proliferation of GP88 overexpressing breast cancer cells. Mouse xenograft experiments in athymic ovariectomized nude mice showed that GP88 over expressing cells were fulvestrant resistant in vivo in contrast to low GP88 expressing cells. We show that the ability of fulvestrant to induce apoptosis determined by measuring cleavage of poly (ADP-ribose) polymerase was inhibited by GP88. Anti-apoptotic activity of GP88 was associated with sustained expression of bcl-2 and bcl-xL after fulvestrant treatment. In contrast, fulvestrant was still able to inhibit the ability of estrogen to stimulate ERE-luciferase reporter gene activity as well as vEGF expression in GP88 over expressing MCF-7 cells similarly to control MCF-7 cells. Collectively, our data suggest that GP88 prevents apoptosis induced by faslodex and contributes to antiestrogen resistance in human breast cancer.展开更多
Although a wide range of studies have addressed the relationship between estrogen receptor(ER) expression and prognosis in non-small cell lung cancer(NSCLC), that relationship remains controversial. This is in large p...Although a wide range of studies have addressed the relationship between estrogen receptor(ER) expression and prognosis in non-small cell lung cancer(NSCLC), that relationship remains controversial. This is in large part because there is no consensus on the rate of ER expression in NSCLC or on the intracellular distribution of ER expression. This suggests that establishing the relationship between ER expression and prognosis will require standardization of the antibodies used as well as the definition of a positive response. For example, it is supposed from previous studies that ERs in the cytoplasm and nucleus have different relationships to prognosis than ERs in the cytoplasm. Moreover, ER signaling in NSCLC is known to be affected by aromatase, progesterone receptor and epidermal growth factor receptor mutation. However, there has been little functional analysis these mutants and subtypes. This review will focus on what is known about the role of ERs in NSCLC and whether ER can be a useful prognostic marker or therapeutic target in NSCLC.展开更多
The role of hormone therapy in the treatment of ovarian cancer is not clear. Data on the efficacy and safety of antiestrogens and aromatase inhibitors in recurrent ovarian cancer have been accumulated through phase Ⅱ...The role of hormone therapy in the treatment of ovarian cancer is not clear. Data on the efficacy and safety of antiestrogens and aromatase inhibitors in recurrent ovarian cancer have been accumulated through phase Ⅱ clinical studies. Most of these studies were conducted in platinum-resistant recurrent ovarian cancer, and although complete response rates were not high, reported adverse events were low. If administered to patients who are positive for estrogen receptors, hormone therapy may become a viable option for the treatment of recurrent ovarian cancer.展开更多
基金supported by grants from the National Key R&D Program of China(Grant No.2018YFC0115204)the National Natural Science Foundation of China(Grant No.81672634)+3 种基金the Chinese Society of Clinical Oncology Foundation(Grant No.Y-2019AZMS-0377)the Beijing Medical Award Foundation(Grant No.YXJL-2020-0941-0763)Beijing Hope Run Special Fund of Cancer Foundation of China(Grant No.LC2019B16)Beijing Xisike Clinical Oncology Research Foundation(Grant No.Y-pirrefabre202101-0008).
文摘Objective:Endocrine therapy with fulvestrant has shown synergistic antitumor effects with some chemotherapy drugs in vitro.This study evaluated the efficacy and safety of fulvestrant with vinorelbine in patients with hormone receptor positive(HR+)/human epidermal growth factor receptor-2-negative(HER2−)recurrent or metastatic breast cancer.Methods:Patients were intramuscularly administered fulvestrant 500 mg(day 1 per cycle for 28 days)and oral vinorelbine(60 mg/m2 on days 1,8,and 15 of each cycle).The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival,objective response rate,disease control rate,duration of response,and safety.Results:A total of 38 patients with HR+/HER2−advanced breast cancer included in the study were followed up for a median time of 25.1 months.The overall median PFS was 9.86 months[95%confidence interval(CI)7.2-23.13],and the median PFS of the first-line and the second-line treatment population was 20.73 months(95%CI 9.82 to NR)and 4.27 months(95%CI 3.68 to NR),respectively.Most adverse events reported were of grade 1/2,and none were of grade 4/5.Conclusions:This is the first exploratory study of a fulvestrant and oral vinorelbine regimen in the treatment of HR+/HER2−recurrent and metastatic breast cancer.The combination chemo-endocrine therapy was efficacious,safe,and promising for patients with HR+/HER2−advanced breast cancer.
文摘For the quantitative determination of Fulvestrant, Benzyl alcohol, and Benzyl benzoate in Fulvestrant injection, an original RP-HPLC approach was developed. The gradient method was developed using HPLC and a Phenomenex Luna C8, 150 × 4.6 mm, i.d 3.0 μm particle size column with a gradient programme of mobile phases A and B. With a flow rate of 1.5 mL/minute, injection volume of 10 μL, and column temperature of 35°C, UV wavelength detection at 254 nm for Benzyl alcohol and Benzoyl Benzoate and 280 nm for Fulvestrant, mobile phase-A consists of DI water and mobile phase-B consists of Acetonitrile. The current study describes a single HPLC method for developing a Fulvestrant (Active), Benzyl alcohol (Cosolvent), and Benzyl Benzoate (Cosolvent) assay for Fulvestrant injection. The assay method was determined to be suitable for quantifying three components in the pharmaceutical product and was verified according to ICH guidelines.
文摘The 88 kDa glycoprotein known as GP88, Progranulin or PC cell derived growth factor is an autocrine growth factor with a unique cysteine rich motif that is over expressed in breast cancer whereas it is negative in normal mammary epithelial cells. It has been shown to play a major role in estrogen independence, tamoxifen resistance and tumorigenesis of breast cancer cells. In the present study, we investigated the effect of GP88 overexpression on the response of the human breast cancer MCF-7 cells to the pure estrogen receptor antagonist fulvestrant (ICI 182,780). While fulvestrant effectively inhibited cell proliferation of empty vector transfected cells, it had no inhibitory effect on the proliferation of GP88 overexpressing breast cancer cells. Mouse xenograft experiments in athymic ovariectomized nude mice showed that GP88 over expressing cells were fulvestrant resistant in vivo in contrast to low GP88 expressing cells. We show that the ability of fulvestrant to induce apoptosis determined by measuring cleavage of poly (ADP-ribose) polymerase was inhibited by GP88. Anti-apoptotic activity of GP88 was associated with sustained expression of bcl-2 and bcl-xL after fulvestrant treatment. In contrast, fulvestrant was still able to inhibit the ability of estrogen to stimulate ERE-luciferase reporter gene activity as well as vEGF expression in GP88 over expressing MCF-7 cells similarly to control MCF-7 cells. Collectively, our data suggest that GP88 prevents apoptosis induced by faslodex and contributes to antiestrogen resistance in human breast cancer.
文摘Although a wide range of studies have addressed the relationship between estrogen receptor(ER) expression and prognosis in non-small cell lung cancer(NSCLC), that relationship remains controversial. This is in large part because there is no consensus on the rate of ER expression in NSCLC or on the intracellular distribution of ER expression. This suggests that establishing the relationship between ER expression and prognosis will require standardization of the antibodies used as well as the definition of a positive response. For example, it is supposed from previous studies that ERs in the cytoplasm and nucleus have different relationships to prognosis than ERs in the cytoplasm. Moreover, ER signaling in NSCLC is known to be affected by aromatase, progesterone receptor and epidermal growth factor receptor mutation. However, there has been little functional analysis these mutants and subtypes. This review will focus on what is known about the role of ERs in NSCLC and whether ER can be a useful prognostic marker or therapeutic target in NSCLC.
基金Supported by The Karoji Memorial Fund of the Hirosaki University Graduate School of Medicine
文摘The role of hormone therapy in the treatment of ovarian cancer is not clear. Data on the efficacy and safety of antiestrogens and aromatase inhibitors in recurrent ovarian cancer have been accumulated through phase Ⅱ clinical studies. Most of these studies were conducted in platinum-resistant recurrent ovarian cancer, and although complete response rates were not high, reported adverse events were low. If administered to patients who are positive for estrogen receptors, hormone therapy may become a viable option for the treatment of recurrent ovarian cancer.
