Clinical activity of chronic oral etoposide in previously treated metastatic breast cancer.

Martin, Mallory; Lluch, Aña; Casado, Antonio; Santabárbara, P.; Adrover, Encarna; Valverde, José María; Lopez-Martin, J.A.; Rodriguez-Lescure, A.; Azagra, P.; Garcı́a-Conde, J

doi:10.1200/jco.1994.12.5.986

Cited by 55 publications

(27 citation statements)

References 12 publications

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“…Although doxorubicin has been most widely used, there is evidence of the efficacy of these agents in the treatment of breast cancer (26,27). Additionally, with recent reports of the expression of HER2 in other malignancies including gastrointestinal cancer, it is important to understand the interaction of trastuzumab with a variety of chemotherapeutic agents.…”

Section: Introductionmentioning

confidence: 99%

Involvement of the HER2 pathway in repair of DNA damage produced by chemotherapeutic agents

Boone

Bhosle

Tilby

et al. 2009

Molecular Cancer Therapeutics

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HER2 (ErbB2) is overexpressed in up to 30% of human breast cancers. Preclinical and clinical studies suggest synergy between some chemotherapeutic agents and the humanized anti-HER2 antibody trastuzumab (Herceptin). This study investigated the effects of etoposide and cisplatin on the repair of DNA damage in breast cancer cell lines. We examined the potential significance of HER2 nuclear expression in DNA repair. MCF-7, SK-BR-3, and MDA-MB-453 cells were treated with cisplatin and etoposide. Repair of DNA interstrand crosslinks (ICL) and strand breaks, following incubation with cisplatin and etoposide, respectively, were quantitated by the single-cell gel electrophoresis (comet) assay. Intrastrand crosslinks produced by cisplatin were assessed by ELISA. The effects of trastuzumab were measured in combination with these drugs. Similar experiments were done using HER2-negative MDA-MB-468 cells transfected with HER2 and a construct lacking the nuclear localization sequence. Incubation of breast cancer cell lines with trastuzumab delayed the repair of ICL produced by cisplatin. There were no effects on the repair of intrastrand crosslinks produced by cisplatin, or repair of DNA strand breaks following etoposide treatment. Transfection of HER2 into MDA-MB-468 cells inhibited the repair of cisplatin-induced ICL, whereas transfection of a HER2 construct lacking the nuclear localization sequence did not affect DNA repair. These results indicate that HER2 expression modulates the repair of specific DNA lesions produced by chemotherapy. The effect on ICL repair requires nuclear expression of HER2. Understanding the mechanisms of interaction between DNA-interacting agents and HER2 inhibitors will inform the design of clinical trials and optimize the therapeutic effects of these combinations.

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Section: Introductionmentioning

confidence: 99%

Involvement of the HER2 pathway in repair of DNA damage produced by chemotherapeutic agents

Boone

Bhosle

Tilby

et al. 2009

Molecular Cancer Therapeutics

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“…Included studies were published between 1993 and 2015 and reported on a total of 483 patients ( Table 2). All studies except one that was retrospective (7), had a prospective phase II, non-randomized, one arm design (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Besides two studies that were from China (17,18), all other reports originated from Europe and the United States ( Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…In the third study that included only patients receiving etoposide as a second or later line treatment, RR were 28.6% (four of 14 patients) in the second line, 35.8% (19 of 53 patients) in the third line, and 54.2% in the fourth or later line (15). Three studies reported on responses in different metastatic sites (11,12,15) and noticed that a variety of metastatic sites were among the responding sites. Another study performed a PFS analysis according to metastatic site and reported that patients with visceral metastases had a worse PFS than the rest of the populations in the study (18).…”

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confidence: 99%

A Systematic Review and Pooled Analysis of Studies of Oral Etoposide in Metastatic Breast Cancer

Voutsadakis¹

2018

Eur J Breast Health

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“…Following the emergence of oral etoposide, the role of prolonged oral etoposide in the treatment of breast cancer was investigated in five phase II trials (Calvert et al, 1993;Martin et al, 1994;Palombo et al, 1994;Atienza et al, 1995;Bontenbal et al, 1995). Unlike the results of single agent i.v.…”

Section: Discussionmentioning

confidence: 99%

Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel in patients with advanced breast cancer pretreated with anthracyclines: a randomised phase III trial of Turkish Oncology Group

et al. 2005

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Our objective was to determine whether oral etoposide and cisplatin combination (EoP) is superior to paclitaxel in the treatment of advanced breast cancer (ABC) patients pretreated with anthracyclines. From December 1997 to August 2003, 201 patients were randomised, 100 to EoP and 101 to paclitaxel arms. Four patients in each arm were ineligible. The doses of etoposide and cisplatin were 50 mg p.o. twice a day for 7 days and 70 mg m À2 intravenously (i.v.) on day 1, respectively, and it was 175 mg m À2 on day 1 for paclitaxel. Both treatments were repeated every 3 weeks. A median of four cycles of study treatment was given in both arms. The response rate obtained in the EoP arm was significantly higher (36.3 vs 22.2%; P ¼ 0.038). Median response duration was longer for the EoP arm (7 vs 4 months) (P ¼ 0.132). Also, time to progression was significantly in favour of the EoP arm (5.5 vs 3.9 months; P ¼ 0.003). Median overall survival was again significantly longer in the EoP arm (14 vs 9.5 months; P ¼ 0.039). Toxicity profile of both groups was similar. Two patients in each arm were lost due to febrile neutropenia. The observed activity and acceptable toxicity of EoP endorses the employment of this combination in the treatment of ABC following anthracyclines.

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Clinical activity of chronic oral etoposide in previously treated metastatic breast cancer.

Abstract: Chronic oral etoposide appears to be an active and well-tolerated regimen in MBC patients previously exposed to chemotherapy. This schedule of etoposide administration warrants further studies, alone or in combination, in MBC.

Cited by 55 publications

References 12 publications

Involvement of the HER2 pathway in repair of DNA damage produced by chemotherapeutic agents

Involvement of the HER2 pathway in repair of DNA damage produced by chemotherapeutic agents

A Systematic Review and Pooled Analysis of Studies of Oral Etoposide in Metastatic Breast Cancer

Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel in patients with advanced breast cancer pretreated with anthracyclines: a randomised phase III trial of Turkish Oncology Group

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