Chronic oral etoposide in advanced breast cancer

Palombo, H; Vila, Jordi; Viñolas, Núria; Jj, Grau; Jm, Mañé; Daniels, M.; Mellado, Begoña

doi:10.1007/bf00686513

Cited by 21 publications

(4 citation statements)

References 14 publications

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“…In advanced breast cancer, metronomic chemotherapy has been shown to provide disease control with a lower incidence of adverse events compared to conventional chemotherapy at the maximum tolerated dose [33,34]. From 1994 to 2000, oral VP16 showed interesting clinical activity in patients with MBC after multiple lines of treatment [35][36][37][38][39]. More recently, a study by Cabel et al [12] showed survival rates with oral VP16 comparable to other treatment lines including capecitabine, paclitaxel, eribulin, and anthracycline (median PFS of 3.2 months) in patients with HER2-negative MBC.…”

Section: Discussionmentioning

confidence: 99%

Oral Etoposide and Trastuzumab Use for HER2-Positive Metastatic Breast Cancer: A Retrospective Study from the Institut Curie Hospitals

Chalumeau

Carton

Eeckhoutte

et al. 2022

Cancers

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Background: The TOP2A and ERBB2 genes are co-amplified in about 40% of HER2 positive (HER2+) breast cancers. Oral etoposide (VP16), an inhibitor of topoisomerase-II (encoded by TOP2A), has demonstrated clinical activity in metastatic breast cancer (MBC). The benefit of oral VP16 combined with trastuzumab (VP16-T) in HER2+ MBC has not yet been evaluated. Methods: Patients treated at the Institut Curie Hospitals with VP16-T for HER2+ MBC were retrieved by an in silico search. Progression-free survival (PFS), overall survival (OS), response rate, prolonged PFS (defined as at least 6 months), clinical benefit, and toxicity were assessed. The co-amplification of ERBB2 and TOP2A was assessed by shallow whole genome sequencing on tumor tissue whenever available. Results: Forty-three patients received VP16-T after a median number of six prior treatment lines for HER2+ MBC. Median PFS and OS were 2.9 months (95% CI [2.4–4.7]) and 11.3 months (95% CI [8.3–25.0]), respectively. Three patients had a complete response, while 12/40 (30%) experienced clinical benefit. Only three patients stopped treatment for toxicity. Seven (35%) patients displayed a TOP2A/ERBB2 co-amplification. No statistically significant correlation was found between outcome and TOP2A/ERBB2 co-amplification. Conclusion: Our analysis suggests a favorable efficacy and toxicity profile for VP16-T in patients with heavily pretreated HER2+ MBC.

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Section: Discussionmentioning

confidence: 99%

Oral Etoposide and Trastuzumab Use for HER2-Positive Metastatic Breast Cancer: A Retrospective Study from the Institut Curie Hospitals

Chalumeau

Carton

Eeckhoutte

et al. 2022

Cancers

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“…Bontenbal also used etoposide with 50 mg/m2 orally for first 21 days of 28 days in 27 pretreated metastatic breast cancer patients, achieving a CBR of 43% [89]. Another two-phase II trial used the same scheme in 43 and 18 pretreated metastatic breast cancer patients; ORR of 35% and PR of 21% were reported, respectively [90, 91]. The same regimen was used as a first-line drug in metastatic patients; one CR and five PR were obtained [92].…”

Section: Resultsmentioning

confidence: 99%

Metronomic Chemotherapy: A Systematic Review of the Literature and Clinical Experience

Şimşek

Esin

Yalçın

2019

Journal of Oncology

101

100

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Metronomic chemotherapy, continuous and dose-dense administration of chemotherapeutic drugs with lowered doses, is being evaluated for substituting, augmenting, or appending conventional maximum tolerated dose regimens, with preclinical and clinical studies for the past few decades. To date, the principle mechanisms of its action include impeding tumoral angiogenesis and modulation of hosts’ immune system, affecting directly tumor cells, their progenitors, and neighboring stromal cells. Its better toxicity profile, lower cost, and easier use are main advantages over conventional therapies. The evidence of metronomic chemotherapy for personalized medicine is growing, starting with unfit elderly patients and also for palliative treatment. The literature reviewed in this article mainly demonstrates that metronomic chemotherapy is advantageous for selected patients and for certain types of malignancies, which make it a promising therapeutic approach for filling in the gaps. More clinical studies are needed to establish a solidified role for metronomic chemotherapy with other treatment models in modern cancer management.

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“…Neskovic-Konstantinovic et al 14 reported a response rate of 33% in previously untreated MBC patients. Martin et al 15 and Palombo et al 18 observed ORRs of 30% and 22%, respectively, in patients who had received 1 prior chemotherapy regimen. However, in a phase 2 clinical trial, a response rate of only 10% was achieved in patients who had failed 1 previous chemotherapy regimen.…”

Section: Discussionmentioning

confidence: 97%

“… 12 , 13 Furthermore, the prolonged schedule of administration of single-agent oral etoposide has been tested in recurrent or MBC in five phase 2 clinical trials. 14 – 18 The numbers of patients enrolled and the response rates in these studies are listed in Table 1 . It is important to note that all of these studies included small sample sizes and were conducted before granulocyte colony-stimulating factor was used in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Oral Etoposide in Pretreated Metastatic Breast Cancer

Yuan

Zhang

et al. 2015

Medicine

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No standard chemotherapy has been defined for metastatic breast cancer (MBC) patients pretreated with anthracyclines and taxanes. A multicenter phase 2 study was conducted to evaluate the safety and efficacy of oral etoposide in patients with MBC.Eligible patients were treated with repeated cycles of oral etoposide (60 mg/m2/d on days 1–10, followed by 11 days of rest). The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate, clinical benefit rate (CBR), and toxicity profiles.Seventy-five women with MBC were enrolled at 10 centers in China. Seven (9.3%) patients achieved partial response (PR) and 29 (38.7%) had stable disease (SD). Nine patients (12%) had SD for >24 weeks and the CBR was 21.3% (16/75). The median PFS was 4.5 (range, 1.3–7.7) months. Of the 38 patients who received ≥3 regimens prior to this study, 2 (5.3%) had PR and 3 (7.9%) had SD for >24 weeks, with a CBR of 13.2%. The reported grade 3/4 adverse events included leukopenia (13.3%, n = 10), neutropenia (17.9%, n = 14), anemia (2.7%, n = 2), vomiting (2.6%, n = 2), and alopecia (1.3%, n = 1).Oral etoposide was effective and well tolerated in Chinese women with pretreated MBC.

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Chronic oral etoposide in advanced breast cancer

Cited by 21 publications

References 14 publications

Oral Etoposide and Trastuzumab Use for HER2-Positive Metastatic Breast Cancer: A Retrospective Study from the Institut Curie Hospitals

Oral Etoposide and Trastuzumab Use for HER2-Positive Metastatic Breast Cancer: A Retrospective Study from the Institut Curie Hospitals

Metronomic Chemotherapy: A Systematic Review of the Literature and Clinical Experience

Efficacy of Oral Etoposide in Pretreated Metastatic Breast Cancer

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