Pegylated liposomal doxorubicin in combination with cyclophosphamide and trastuzumab in HER2-positive metastatic breast cancer patients: efficacy and cardiac safety from the GEICAM/2004–05 study

Martín, Miguel; Sánchez‐Rovira, Pedro; Muñoz, Montserrat; Baena-Cañada, José Manuel; Mel, J. R.; Margelı́, Mireia; Ramos, Manuel; Martínez, E.; García-Sáenz, José Ángel; Casado, Antonio; Jaén, A.; González-Farré, X.; Escudero, M.J.; Rodriguez-Martin, C; Carrasco, Eva

doi:10.1093/annonc/mdr024

Cited by 32 publications

(21 citation statements)

References 22 publications

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“…In this clinical context, cyclophosphamide is an important candidate among possible combination partners because of its well-established effectiveness in combination with the free drug doxorubicin for the treatment of early-stage as well as metastatic breast cancer, both in HER2-positive and in HER2-negative disease (41,42). More recently, cyclophosphamide has also shown promising clinical responses when combined with PLD in HER2-negative patients with metastatic breast cancer (30) as well as in HER2-positive patients with metastatic breast cancer in combination with PLD and trastuzumab (28,29).…”

Section: Discussionmentioning

confidence: 99%

“…Cyclophosphamide is a widely used drug in breast cancer therapy and combines effectively with doxorubicin. Furthermore, recent clinical data indicate that cyclophosphamide likewise combines well with liposomal doxorubicin and trastuzumab in HER2-positive breast cancer, with observed overall response rates of about 69% and good tolerability (28,29). Current clinical approaches suggest administration of cyclophosphamide and liposomal doxorubicin on the same day every 3 or 4 weeks for the treatment of patients with breast cancer (28)(29)(30).…”

Section: Introductionmentioning

confidence: 99%

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Cyclophosphamide-Mediated Tumor Priming for Enhanced Delivery and Antitumor Activity of HER2-Targeted Liposomal Doxorubicin (MM-302)

Geretti

Leonard

Dumont

et al. 2015

Molecular Cancer Therapeutics

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Given the bulky nature of nanotherapeutics relative to small molecules, it is hypothesized that effective tumor delivery and penetration are critical barriers to their clinical activity. HER2-targeted PEGylated liposomal doxorubicin (MM-302, HER2-tPLD) is an antibody-liposomal drug conjugate designed to deliver doxorubicin to HER2-overexpressing cancer cells while limiting uptake into nontarget cells. In this work, we demonstrate that the administration and appropriate dose sequencing of cyclophosphamide can improve subsequent MM-302 delivery and enhance antitumor activity in preclinical models without negatively affecting nontarget tissues, such as the heart and skin. We demonstrate that this effect is critically dependent on the timing of cyclophosphamide administration. Furthermore, the effect was found to be unique to cyclophosphamide and related analogues, and not shared by other agents, such as taxanes or eribulin, under the conditions examined. Analysis of the cyclophosphamide-treated tumors suggests that the mechanism for improved MM-302 delivery involves the induction of tumor cell apoptosis, reduction of overall tumor cell density, substantial lowering of interstitial fluid pressure, and increasing vascular perfusion. The novel dosing strategy for cyclophosphamide described herein is readily translatable to standard clinical regimens, represents a potentially significant advance in addressing the drug delivery challenge, and may have broad applicability for nanomedicines. This work formed the basis for clinical evaluation of cyclophosphamide for improving liposome deposition as part of an ongoing phase I clinical trial of MM-302 in HER2-positive metastatic breast cancer. Mol Cancer Ther; 14(9); 2060-71. Ó2015 AACR.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cyclophosphamide-Mediated Tumor Priming for Enhanced Delivery and Antitumor Activity of HER2-Targeted Liposomal Doxorubicin (MM-302)

Geretti

Leonard

Dumont

et al. 2015

Molecular Cancer Therapeutics

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“…Еще одна комбинация на основе ПЛД (ПЛД + циклофосфамид + трастузумаб) была изучена при HER-2+ мРМЖ в исследовании II фазы GEI-CAM / 2004-05 [43]. В группе из 48 оцененных паци-енток зарегистрирована очень высокая непосредствен-ная эффективность режима (ЧОО 68,8 %, включая 2 ' 2 0 1 6 Том 12 / Vol.…”

Section: таким образом добавление плд к доцетакселу в 1-й линии хт мunclassified

Place of pegylated liposomal doxorubicin in the therapy of metastatic breast cancer

Артамонова¹

2016

Tumors of female reproductive system

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35М а м м о л о г и я / M a m m o l o g y 2 ' 2 0 1 6 Том 12 / Vol. 12 ОПУХОЛИ ЖЕНСКОЙ РЕПРОДУКТИВНОЙ СИСТЕМЫ TUMORS OF FEMALE REPRODUCTIVE SYSTEM Key words: metastatic breast cancer, anthracyclines, pegylated liposomal doxorubicinВведение Метастатический рак молочной железы (мРМЖ) продолжает оставаться неизлечимым заболеванием, и лишь небольшая часть пациенток, как правило, с гормонозависимым типом опухоли, может рассчи-тывать на значительную продолжительность жизни от момента выявления диссеминации. Благодаря на-учным достижениям последних 2 десятилетий в арсе-нале онкологов появилось большое число новых ле-карственных агентов, включающих биологические таргетные препараты. Это позволило улучшить конт-роль роста опухоли и увеличить выживаемость, однако в целом наши успехи в лечении мРМЖ можно оценить как незначительные: медиана выживаемости больных составляет на сегодняшний день 24-36 мес и только 24 % живут более 5 лет [1].Кроме увеличения продолжительности жизни важ-нейшей целью является сохранение ее качества, кото-рое может значительно снизиться в результате нежела-тельных явлений на фоне применения цитостатиков. Комбинации являются более токсичными, чем моно-терапия, и при этом не имеют доказанных преиму-ществ в отношении увеличения общей выживаемости (ОВ), поэтому при мРМЖ рекомендовано последова-тельное назначение монорежимов, по крайней мере начиная со 2-й линии лечения. Так как комбинации обеспечивают большую частоту объективного ответа (ЧОО), эту стратегию следует рассматривать при быс-тром прогрессировании болезни и наличии угрожаю-щих жизни висцеральных метастазов [2][3][4][5][6][7].Не менее серьезным является вопрос о том, когда специфическое противоопухолевое лечение должно

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“…In addition, recent findings from studies of eribulin mesylate and nab-paclitaxel in patients who have received multiple lines of chemotherapy warrant attention. Various other agents-including liposomal doxorubicin, gemcitabine, and (with renewed interest) platinum analogs-have been studied for the treatment of mbc [19][20][21][22][23][24][25][26] . However, although those agents may also be considered potential alternatives for the treatment of mbc, they have not been engaged as the standard of care, and limited prospective data have been generated to enable a systematic review of their efficacy in that setting.…”

Section: Chemotherapy For Mbc: the Current State Of The Artmentioning

confidence: 99%

Advances in the Management of Metastatic Breast Cancer: Options Beyond First-Line Chemotherapy

Ayoub

Verma

2012

Current Oncology

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This article provides an overview of recent advances in chemotherapy that may be used for the treatment of patients with locally advanced or metastatic breast cancer (mbc). Key phase ii and iii trial data for eribulin mesylate, ixabepilone, and nab-paclitaxel, published since 2006, are discussed on the basis of recency, depth, and quality. Eribulin mesylate is the first monotherapy to significantly increase overall survival in patients with pretreated mbc, but nab-paclitaxel offers a novel and safer mode of delivery in comparison with standard taxanes. By contrast, the use of ixabepilone will be limited for now, until the associated neurotoxicity can be better managed. Alongside a brief overview of the other major chemotherapies currently in use, we have aimed to provide a Canadian context for how these novel agents may be integrated into clinical practice.

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Pegylated liposomal doxorubicin in combination with cyclophosphamide and trastuzumab in HER2-positive metastatic breast cancer patients: efficacy and cardiac safety from the GEICAM/2004–05 study

Abstract: The combination of PLD-cyclophosphamide-concurrent trastuzumab is a feasible, safe, and effective first-line regimen for HER2-overexpressing MBC.

Cited by 32 publications

References 22 publications

Cyclophosphamide-Mediated Tumor Priming for Enhanced Delivery and Antitumor Activity of HER2-Targeted Liposomal Doxorubicin (MM-302)

Cyclophosphamide-Mediated Tumor Priming for Enhanced Delivery and Antitumor Activity of HER2-Targeted Liposomal Doxorubicin (MM-302)

Place of pegylated liposomal doxorubicin in the therapy of metastatic breast cancer

Advances in the Management of Metastatic Breast Cancer: Options Beyond First-Line Chemotherapy

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