A Phase II Study of Lipoplatin (Liposomal Cisplatin)/Vinorelbine Combination in HER-2/neu–Negative Metastatic Breast Cancer

Farhat, Fadi; Temraz, Sally; Kattan, Joseph; Ibrahim, Khaled; Bitar, Nizar; Haddad, Nadine; Jalloul, Rahif; Hatoum, Hassan; Nsouli, Ghazi; Shamseddine, Ali

doi:10.1016/j.clbc.2011.08.005

Cited by 37 publications

(20 citation statements)

References 22 publications

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“…Preclinical studies of a liposomal formulation of cisplatin have shown promising effects against ovarian, pancreatic, head and neck cancer, non-small cell lung cancer (NSCLC), and HER-2/neu–negative metastatic breast cancer [53,65,66,67,68]. In ovarian cancer, lipoplatin (liposomal cisplatin) was found to exhibit anti-tumor activity by causing caspase activation and hence apoptosis [65].…”

Section: Alternative Pathways For Accumulation Of Cisplatinmentioning

confidence: 99%

Facilitating the Cellular Accumulation of Pt-Based Chemotherapeutic Drugs

Lambert

Sørensen

2018

IJMS

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Cisplatin, carboplatin, and oxaliplatin are Pt-based drugs used in the chemotherapeutic eradication of cancer cells. Although most cancer patient cells initially respond well to the treatment, the clinical effectiveness declines over time as the cancer cells develop resistance to the drugs. The Pt-based drugs are accumulated via membrane-bound transporters, translocated to the nucleus, where they trigger various intracellular cell death programs through DNA interaction. Here we illustrate how resistance to Pt-based drugs, acquired through limitation in the activity/subcellular localization of canonical drug transporters, might be circumvented by the facilitated uptake of Pt-based drug complexes via nanocarriers/endocytosis or lipophilic drugs by diffusion.

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Section: Alternative Pathways For Accumulation Of Cisplatinmentioning

confidence: 99%

Facilitating the Cellular Accumulation of Pt-Based Chemotherapeutic Drugs

Lambert

Sørensen

2018

IJMS

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“…Only recently Farhat and coworkers reported the results of their phase II trial of lipoplatin and vinorelbine combination in patients with HER-2 negative metastatic breast cancer who had not received prior treatment in an advanced setting [23]. A 53.1% ORR was reported (CR in 3 patients, 9.4%) and 37.5% patients showed stable disease.…”

Section: Platinum and Lipoplatinum Experiencementioning

confidence: 99%

Triple Negative Breast Cancer Treatment: Use of Platinum and Platinum Analogs

Fantini¹,

Santelmo²,

Drudi³

et al. 2012

JCT

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Triple negative breast cancer (TNBC) is characterized by a high sensitivity to antiblastic drugs and a high pathological complete remission rate after neoadjuvant therapy. In patients showing complete remission, the probability of developing metastatic disease would seem to be reduced. Nonetheless, this cancer has a high percentage of relapse. Anthracyclines, taxanes and platinum compounds are the most effective drugs for the treatment of TNBC. There is substantial evidence to support the efficacy of platinum-based chemotherapy, probably attributable to the mechanism of action of such drugs, which react with the DNA repair system. PARP inhibitors would also seem to be very interesting. Despite promising results, TNBC remains a disease with a poor prognosis due to the lack of targeted therapy. The discovery of new targets and new agents is thus a high priority issue for this type of breast cancer. In this respect, lipoplatin has been identified as a potentially interesting treatment option to evaluate in both neoadjuvant and advanced settings.

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“…It has shown similar efficacy as cisplatin in pancreatic, head and neck cancer, NSCLC, and HER-2/ neu-negative metastatic breast cancer with a major benefit of a strongly reduced toxicity (6,7).…”

Section: Introductionmentioning

confidence: 99%

Preclinical Activity of the Liposomal Cisplatin Lipoplatin in Ovarian Cancer

Casagrande

Celegato

Borghese

et al. 2014

Clinical Cancer Research

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Purpose: Cisplatin and its platinum derivatives are first-line chemotherapeutic agents in the treatment of ovarian cancer; however, treatment is associated with tumor resistance and significant toxicity. Here we investigated the antitumoral activity of lipoplatin, one of the most promising liposomal platinum drug formulations under clinical investigation.Experimental Design: In vitro effects of lipoplatin were tested on a panel of ovarian cancer cell lines, sensitive and resistant to cisplatin, using both two-dimensional (2D) and 3D cell models. We evaluated in vivo the lipoplatin anticancer activity using tumor xenografts.Results: Lipoplatin exhibited a potent antitumoral activity in all ovarian cancer cell lines tested, induced apoptosis, and activated caspase-9, -8, and -3, downregulating Bcl-2 and upregulating Bax. Lipoplatin inhibited thioredoxin reductase enzymatic activity and increased reactive oxygen species accumulation and reduced EGF receptor (EGFR) expression and inhibited cell invasion. Lipoplatin demonstrated a synergistic effect when used in combination with doxorubicin, widely used in relapsed ovarian cancer treatment, and with the albumin-bound paclitaxel, Abraxane. Lipoplatin decreased both ALDH and CD133 expression, markers of ovarian cancer stem cells. Multicellular aggregates/spheroids are present in ascites of patients and most contribute to the spreading to secondary sites. Lipoplatin decreased spheroids growth, vitality, and cell migration out of preformed spheroids. Finally, lipoplatin inhibited more than 90% tumor xenograft growth with minimal systemic toxicity, and after the treatment suspension, no tumor progression was observed.

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A Phase II Study of Lipoplatin (Liposomal Cisplatin)/Vinorelbine Combination in HER-2/neu–Negative Metastatic Breast Cancer

Cited by 37 publications

References 22 publications

Facilitating the Cellular Accumulation of Pt-Based Chemotherapeutic Drugs

Facilitating the Cellular Accumulation of Pt-Based Chemotherapeutic Drugs

Triple Negative Breast Cancer Treatment: Use of Platinum and Platinum Analogs

Preclinical Activity of the Liposomal Cisplatin Lipoplatin in Ovarian Cancer

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