Phase II study of liposomal cisplatin (Lipoplatin™) plus gemcitabine versus cisplatin plus gemcitabine as first line treatment in inoperable (stage IIIB/IV) non-small cell lung cancer

Mylonakis, N.; Athanasiou, A E; Ziras, Nikolaos; Angel, J. H.; Rapti, Aggeliki; Lampaki, Sofia; Politis, N.; Karanikas, Chrisanthi A.; Kosmas, Christos

doi:10.1016/j.lungcan.2009.06.017

Cited by 81 publications

(48 citation statements)

References 36 publications

(36 reference statements)

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“…Sterically stabilized lipospomal variants of doxorubicin and cisplatin are commercially available and have been shown to exhibit higher therapeutic efficacy or at least better tolerability than the free drugs. Both agents have so far been successfully tested against various solid tumors including breast cancer (Rivera 2003, O'Brien 2008), Kaposi's sarcoma (Coukell & Spencer 1997, Sharpe et al 2002, non-squamous non-small-cell lung cancer (Mylonakis et al 2009, Stathopoulos et al 2011, and pancreatic cancer (Stathopoulos et al 2006), among others. Recently, we have demonstrated an extraordinary uptake phenomenon of liposomes, specifically in adrenocortical tumor cells (Hantel et al 2010(Hantel et al , 2012.…”

Section: Introductionmentioning

confidence: 99%

Liposomal polychemotherapy improves adrenocortical carcinoma treatment in a preclinical rodent model

Hantel¹,

Jung²,

Mussack³

et al. 2014

Endocrine-Related Cancer

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Owing to high relapse rates and early metastatic spread, prognosis in adrenocortical carcinoma (ACC) patients remains poor, highlighting the importance of developing new treatment alternatives for them. Recently, polychemotherapy regimens including etoposide, doxorubicin, and cisplatin together with mitotane (EDP-M) have been defined as the standard treatment for late-stage disease patients. Nevertheless, the administration of conventional cytostatic drugs is associated with severe and dose-limiting side effects. In an attempt to optimize existing clinical treatment regimens, in this study, we investigated the therapeutic efficacy of EDP-M in comparison with that of a paclitaxel-modified scheme (paclitaxel, doxorubicin, cisplatin plus mitotane (PDP-M)) in preclinical in vitro and in vivo models. In addition, based on an extraordinary uptake phenomenon of liposomes in ACC cells, we further evaluated liposomal variants of these protocols (etoposide, liposomal doxorubicin, liposomal cisplatin plus mitotane (LEDP-M) and nab-paclitaxel, liposomal doxorubicin, liposomal cisplatin plus mitotane (LPDP-M)). In vitro, PDP-M was more potent in the induction of apoptosis and inhibition of cell viability as well as cell proliferation than EDP-M. Following the administration of a single therapeutic cycle, we further demonstrated that LEDP-M and LPDP-M exerted significant antitumoral effects in vivo, which were not as evident upon EDP-M and PDP-M treatments. These results were confirmed in a long-term experiment, in which the highest and sustained antitumoral effects were observed for LEDP-M. In summary, liposomal cytostatic substances could represent a promising option that deserves testing in appropriate clinical protocols for the treatment of ACC patients.

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Section: Introductionmentioning

confidence: 99%

Liposomal polychemotherapy improves adrenocortical carcinoma treatment in a preclinical rodent model

Hantel¹,

Jung²,

Mussack³

et al. 2014

Endocrine-Related Cancer

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“…3 However, in clinics, current approaches for NSCLC therapy are still limited to surgical resection, radiotherapy, chemotherapy, or their combinations. 4,5 These are highly aggressive or nonspecific, and are often accompanied by undesirable side effects and toxicity because the anticancer agents show conspicuous cytotoxicity to normal cells and tissues. 6,7 The promises of nanotechnology in cancer research lie in the potential to solve these problems.…”

Section: Introductionmentioning

confidence: 99%

Paclitaxel-loaded poly(glycolide-co-ε-caprolactone)-b-D-α-tocopheryl polyethylene glycol 2000 succinate nanoparticles for lung cancer therapy

Zhao¹,

Chen²,

Yan³

et al. 2013

IJN

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Abstract:In order to improve the therapeutic efficacy and minimize the side effects of lung cancer chemotherapy, the formulation of paclitaxel-loaded poly(glycolide-co-ε-caprolactone)-b-D-α-tocopheryl polyethylene glycol 2000 succinate nanoparticles (PTX-loaded [PGA-co-PCL]-b-TPGS 2k NPs) was prepared. The novel amphiphilic copolymer (PGA-co-PCL)-b-TPGS 2k was synthesized by ring-opening polymerization and characterized by proton nuclear magnetic resonance spectroscopy and gel permeation chromatography. The PTX-loaded (PGA-co-PCL)-b-TPGS 2k NPs were characterized in terms of size, size distribution, zeta potential, drug encapsulation, surface morphology, and drug release. In vitro cellular uptakes of NPs were investigated with confocal laser scanning microscopy, indicating the coumarin 6-loaded (PGA-co-PCL)-b-TPGS 2k NPs could be internalized by human lung cancer A-549 cells. The antitumor effect of PTX-loaded NPs was evaluated, both in vitro and in vivo, on an A-549 cell tumor-bearing mouse model via intratumoral injection. The commercial PTX formulation Taxol was chosen as the reference. Experimental results showed that the PTX-loaded NPs possessed higher cytotoxicity and could effectively inhibit the growth of tumor. All the results suggested that amphiphilic copolymer (PGA-co-PCL)-b-TPGS 2k could act as a potential biological material for nanoformulation in the treatment of lung cancer.

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“…In conclusion, replacing cisplatin with lipoplatin in aggressive cisplatin-resistant patients with ovarian cancer would add the advantage of lower toxicities as already shown in randomized phase II and III studies in NSCLC (48)(49)(50). Adding the advantage of reducing the metastatic potential and the putative ovarian CSCs, and its synergistic activity with Abraxane and doxorubicin, lipoplatin in combination with Abraxane or doxorubicin should be compared with cisplatin þ Abraxane/doxorubicin in a randomized clinical study against ovarian cancer.…”

Section: Discussionmentioning

confidence: 91%

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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Phase II study of liposomal cisplatin (Lipoplatin™) plus gemcitabine versus cisplatin plus gemcitabine as first line treatment in inoperable (stage IIIB/IV) non-small cell lung cancer

Cited by 81 publications

References 36 publications

Liposomal polychemotherapy improves adrenocortical carcinoma treatment in a preclinical rodent model

Liposomal polychemotherapy improves adrenocortical carcinoma treatment in a preclinical rodent model

Paclitaxel-loaded poly(glycolide-co-ε-caprolactone)-b-D-α-tocopheryl polyethylene glycol 2000 succinate nanoparticles for lung cancer therapy

Preclinical Activity of the Liposomal Cisplatin Lipoplatin in Ovarian Cancer

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Phase II study of liposomal cisplatin (Lipoplatin™) plus gemcitabine versus cisplatin plus gemcitabine as first line treatment in inoperable (stage IIIB/IV) non-small cell lung cancer

Cited by 81 publications

References 36 publications

Liposomal polychemotherapy improves adrenocortical carcinoma treatment in a preclinical rodent model

Liposomal polychemotherapy improves adrenocortical carcinoma treatment in a preclinical rodent model

Paclitaxel-loaded poly(glycolide-co-&epsilon;-caprolactone)-b-D-&alpha;-tocopheryl polyethylene glycol 2000 succinate nanoparticles for lung cancer therapy

Preclinical Activity of the Liposomal Cisplatin Lipoplatin in Ovarian Cancer

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Paclitaxel-loaded poly(glycolide-co-ε-caprolactone)-b-D-α-tocopheryl polyethylene glycol 2000 succinate nanoparticles for lung cancer therapy