High-dose tamoxifen in high-hormone-receptor-expressing advanced breast cancer patients: a phase II pilot study

Background: Tumor progression following endocrine therapy is considered to indicate resistance to endocrine drugs due to a variety of mechanisms. An insufficient dose of endocrine drugs is one of the causes for treatment failure in some patients with high hormone-receptor (HR)-expressing advanced breast cancer. This study aimed to explore the efficacy of high-dose tamoxifen (TAM) treatment in patients with advanced breast cancer with highly expressed HR. Materials & methods: This was a single-arm, phase II pilot study that enrolled patients with advanced breast cancer with high HR expression (estrogen receptor ⩾60% and/or progesterone receptor ⩾60%) following routine endocrine therapy. All enrolled patients received a high-dose of TAM (100 mg/day) until disease progression. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and safety. Exploratory endpoints included the predictive value of 16α-18F-17β-fluoroestradiol quantitative positron emission tomography/computed tomography (18F-FES PET/CT) for treatment efficacy. Results: A total of 30 patients were enrolled between September 2017 and February 2019. The median PFS was 6 months [95% confidence interval (CI) 4.9–7.1] and the median OS was 15.6 months (95% CI 8.3–22.9). Five patients experienced a partial response (PR) and none experienced a complete response (CR), with an ORR of 16.7% and CBR of 33.3%. No severe adverse events were observed. Lesions with 18F-FES maximum standardized uptake value (SUVmax) ⩾4 had a significantly longer PFS [median 9.2 months, (95% CI 6.9–11.6)] compared with lesions with a 18F-FES SUVmax <4 [median 4.8 months, (95% CI 3.9–5.6); p = 0.022]. Conclusion: A high-dose of TAM is effective and safe for patients with advanced breast cancer with high HR expression. 18F-FES SUVmax values may predict the local clinical benefits of high-dose TAM . Trial Registration: [ClinicalTrials.gov identifier: NCT0304565]

Download Full-text

Multicenter phase II efficacy trial of toremifene in tamoxifen-refractory patients with advanced breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1993.11.2.345 ◽

1993 ◽

Vol 11 (2) ◽

pp. 345-350 ◽

Cited By ~ 76

Author(s):

C L Vogel ◽

I Shemano ◽

J Schoenfelder ◽

R A Gams ◽

M R Green

Keyword(s):

Breast Cancer ◽

Treatment Failure ◽

Advanced Breast Cancer ◽

Phase Ii ◽

Stable Disease ◽

Objective Response ◽

Metastatic Breast ◽

Advanced Breast ◽

Cross Resistance ◽

High Dose

PURPOSE To explore further the efficacy of high-dose toremifene in patients with advanced breast cancer who had failed to respond to tamoxifen or whose disease had progressed on tamoxifen. PATIENTS AND METHODS One hundred two perimenopausal or postmenopausal women with metastatic breast cancer refractory to tamoxifen were entered onto a phase II clinical trial of toremifene at a dose of 200 mg/d. The study patients consisted of 28 primarily refractory patients; 43 patients who had relapsed after a prior tamoxifen response; and 31 patients who had relapsed while receiving adjuvant tamoxifen. This was a heavily pretreated group of patients, with 65% having failed chemotherapeutic attempts and 72% having failed two or more hormonal therapies. Forty-nine percent of patients had visceral dominant disease. RESULTS The objective response rate was 5% (95% confidence interval [CI], 3% to 7%). The median time to treatment failure (TTF) was 10.9 months for the five responders. An additional 23% of patients had stable disease for a median TTF of 7.8 months, whereas the patients who experienced treatment failure had a median TTF of 2.1 months. Whether those patients with stable disease derived clinical benefit or simply had slow progression in an intrinsically indolent disease presentation is uncertain. Common toxicities were generally mild and similar to those encountered with tamoxifen. CONCLUSION We conclude that there is major cross-resistance between tamoxifen and toremifene and that only occasional tamoxifen-refractory patients will have objective responses to toremifene.

Download Full-text

A Phase II Open Label Study of Everolimus in Combination With Endocrine Therapy in Resistant Hormone Receptor-Positive HER2-Negative Advanced Breast Cancer

Clinical Breast Cancer ◽

10.1016/j.clbc.2019.06.005 ◽

2020 ◽

Vol 20 (2) ◽

pp. 89-97 ◽

Cited By ~ 2

Author(s):

Denise A. Yardley ◽

William Liggett ◽

Mark Mainwaring ◽

Aurelio Castrellon ◽

Laura Blakely ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Endocrine Therapy ◽

Phase Ii ◽

Hormone Receptor ◽

Advanced Breast ◽

Open Label ◽

Open Label Study ◽

Label Study ◽

Hormone Receptor Positive

Download Full-text

5072 Independent central review of clinical benefit rates in FIRST: a Phase II comparison of fulvestrant 500 mg with anastrozole 1 mg as first-line endocrine therapy for postmenopausal women with hormone receptor positive advanced breast cancer

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(09)70964-4 ◽

2009 ◽

Vol 7 (2) ◽

pp. 282 ◽

Cited By ~ 1

Author(s):

J.P.O. Lindemann ◽

J.F.R. Robertson ◽

M.J. Ellis ◽

Y. Menu ◽

E.J. Macpherson ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Postmenopausal Women ◽

Endocrine Therapy ◽

Phase Ii ◽

Clinical Benefit ◽

Hormone Receptor ◽

Advanced Breast ◽

First Line ◽

Hormone Receptor Positive

Download Full-text

PALINA: A phase II safety study of palbociclib in combination with letrozole or fulvestrant in African American women with hormone receptor positive HER2 negative advanced breast cancer

Contemporary Clinical Trials Communications ◽

10.1016/j.conctc.2018.05.012 ◽

2018 ◽

Vol 10 ◽

pp. 190-192

Author(s):

Filipa Lynce ◽

Mervat Saleh ◽

Ayesha Shajahan-Haq ◽

Christopher Gallagher ◽

Asma Dilawari ◽

...

Keyword(s):

Breast Cancer ◽

African American ◽

Advanced Breast Cancer ◽

African American Women ◽

Phase Ii ◽

Hormone Receptor ◽

Advanced Breast ◽

Safety Study ◽

American Women ◽

Hormone Receptor Positive

Download Full-text

Everolimus and exemestane in hormone receptor-positive advanced breast cancer: A comprehensive cancer center’s experience.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e13017 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e13017-e13017

Author(s):

Inês Moreira ◽

Marta Ferreira ◽

Ana Afonso ◽

Ana Ferreira ◽

Ana Rodrigues ◽

...

Keyword(s):

Breast Cancer ◽

Adverse Events ◽

Advanced Breast Cancer ◽

Endocrine Therapy ◽

Hormone Receptor ◽

Overall Response Rate ◽

Response Rate ◽

Advanced Breast ◽

Overall Response ◽

Hormone Receptor Positive

e13017 Background: Activation of the mammalian target of rapamycin intracellular signaling pathway is one of the mechanisms of endocrine resistance in breast cancer. The addition of everolimus to exemestane improves progression-free survival (PFS) in patients with hormone receptor positive (HR+) advanced breast cancer (ABC) previously treated with nonsteroidal aromatase inhibitors (NSAIs). The aim of this study was to assess the effectiveness and safety of everolimus plus exemestane in patients with HR+ ABC. Methods: We retrospectively evaluated patients with HR+, HER2 negative ABC treated with everolimus/exemestane that recurred or progressed during/after treatment with NSAIs in a portuguese comprehensive cancer center. Study endpoints were PFS, overall survival (OS), overall response rate and adverse events. Results: Between April 2014 and September 2020, 63 female patients were treated with everolimus/exemestane. Median age was 59 years (36-79), and all had performance status ECOG ≤2. Seventeen (27.0%) patients had bone metastasis alone, 39 (61.9%) had bone and visceral metastasis, 25 (39.7%) had metastasis in 3 or more sites and 87.3% had previous hormone-sensitive disease. Before everolimus/exemestane, 61 (96.8%) patients were being treated with palliative endocrine therapy (alone or in combination with CDK4/6 inhibitors) or chemotherapy (ChT) and 2 (3.2%) patients were under adjuvant endocrine therapy. Median follow-up time was 12.8 months (1.4-74.6), with 39 patients alive. Overall response rate was 14.3% (1 complete response and 8 partial responses) and 45 patients had stable disease. Median PFS was 5.6 months (CI95% 2.4-8.8) and median OS was 25.4 months (CI95% 10.3-40.5). Subgroup analysis regarding PFS was statistically significant for previous treatment with CDK4/6 inhibitors (p = 0.026) and for site of metastasis (p = 0.025). In the subgroup of patients that previously underwent palliative ChT, median PFS was 4.0 months (CI95% 0.2-9.6) and median OS was 18.6 months (CI95% 8.2-29.0). For patients that did not receive previous palliative ChT, median PFS was 5.8 months (CI95% 3.8-7.8) and median OS was 43.5 months (CI95% 2.0-85.0). Grade 3 and 4 adverse events occurred in 21 (33.3%) patients, and were: nausea, anorexia, rash, headache, haematologic toxicity, hepatic cytolysis, hyperglycaemia, pneumonitis, oral mucositis and acute kidney failure with need for haemodialysis. Fifty-five (87.3%) patients suspended everolimus, 34 (54.0%) due to disease progression and 21 (33.3%) due to toxicity. Conclusions: Our results confirm the effectiveness and safety of everolimus/exemestane in real-world setting and support its use mainly before palliative ChT. Everolimus/exemestane in HR+ ABC is feasible in the clinic, with toxicity manageable under close surveillance.

Download Full-text

Cisplatin and VP16 in Metastatic Breast Carcinoma as a Third-Line Chemotherapy: A Randomized Study Comparing Low versus High Doses of Cisplatin

Tumori Journal ◽

10.1177/030089169508100405 ◽

1995 ◽

Vol 81 (4) ◽

pp. 241-244 ◽

Cited By ~ 11

Author(s):

Guido Ceci ◽

Giancarlo Bisagni ◽

Giorgio Cocconi ◽

Carmelina Rodinò ◽

Virginio Belsanti ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Low Dose ◽

Objective Response ◽

Metastatic Breast ◽

Advanced Breast ◽

High Dose ◽

Severe Toxicity ◽

Third Line ◽

Line Chemotherapy

Aims and background The study was designed to define the activity of the combination of cisplatin and etoposide as third-line chemotherapy for advanced breast cancer and to investigate the role of the dosage of cisplatin on the effectiveness of the combination. Methods Ninety-five eligible patients with advanced breast cancer who had failed or relapsed on two previous lines of chemotherapy were randomized to receive cisplatin at a high dose (100 mg/m2 i.v. day 1, arm A) or a low dose (60 mg/m2 day 1, arm B), combined with etoposide (100 mg/m2 i.v. days 4, 6 and 8). Cycles were repeated every 3 weeks. Results Of the 78 patients evaluable for response (39 in arm A and 39 in arm B), 9 (12%) showed complete or partial response, 5 (13%) in the high-dose arm and 4 (10%) in the low-dose arm. One complete response was seen in the high-dose arm and none in the low-dose arm. The only 2 patients with brain involvement showed an objective response (one CR in arm A and one PR in arm B). Median time to progression was 14 weeks in arm A and 10 weeks in arm B, median duration of remission 28 and 34 weeks, and survival 36 and 35 weeks, respectively. The differences were not significant. As expected, the patients in the high-dose arm experienced more severe toxicity. One toxic death was observed in each arm due to sepsis in agranulocytosis. The difference was statistically significant regarding nausea and vomiting. Neurotoxicity and ototoxicity were not relevant problems in this patient setting. Conclusions Considering the very poor prognostic factors presented by these patients, the combination showed a certain activity, and further evaluation in earlier stages of disease is warranted. A particular responsiveness on brain metastases is suggested. The dose of cisplatin was not proven to be of significant importance.

Download Full-text