Dataset Information

Preclinical evaluation of Genexol-PM, a nanoparticle formulation of paclitaxel, as a novel radiosensitizer for the treatment of non-small cell lung cancer.

ABSTRACT: A key research objective in radiation oncology is to identify agents that can improve chemoradiation therapy. Nanoparticle (NP) chemotherapeutics possess several properties, such as preferential accumulation in tumors, that are uniquely suited for chemoradiation therapy. To facilitate the clinical translation of NP chemotherapeutics in chemoradiation therapy, we conducted preclinical evaluation of Genexol-PM, the only clinically approved NP chemotherapeutic with a controlled drug release profile, as a radiosensitizer using non-small cell lung cancer (NSCLC) as a model disease.The physical characteristics and drug release profile of Genexol-PM were characterized. Genexol-PM's efficacy as a radiosensitizer was evaluated in vitro using NSCLC cell lines and in vivo using mouse xenograft models of NSCLC. Paclitaxel dose to normal lung and liver after Genexol-PM administration were quantified and compared with that after Taxol administration.Genexol-PM has a size of 23.91 ± 0.41 nm and surface charge of -8.1 ± 3.1 mV. It releases paclitaxel in a controlled release profile. In vitro evaluation of Genexol-PM as a radiosensitizer showed it is an effective radiosensitizer and is more effective than Taxol, its small molecule counterpart, at the half maximal inhibitory concentration. In vivo study of Genexol-PM as a radiosensitizer demonstrated that it is more effective as a radiosensitizer than Taxol. We also found that Genexol-PM leads to lower paclitaxel exposure to normal lung tissue than Taxol at 6 hours postadministration.We have demonstrated that Genexol-PM is more effective than Taxol as a radiosensitizer in the preclinical setting and holds high potential for clinical translation. Our data support the clinical evaluation of Genexol-PM in chemoradiation therapy for NSCLC.

SUBMITTER: Werner ME

PROVIDER: S-EPMC3750707 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Preclinical evaluation of Genexol-PM, a nanoparticle formulation of paclitaxel, as a novel radiosensitizer for the treatment of non-small cell lung cancer.

Werner Michael E ME Cummings Natalie D ND Sethi Manish M Wang Edina C EC Sukumar Rohit R Moore Dominic T DT Wang Andrew Z AZ

International journal of radiation oncology, biology, physics 20130701 3

<h4>Purpose</h4>A key research objective in radiation oncology is to identify agents that can improve chemoradiation therapy. Nanoparticle (NP) chemotherapeutics possess several properties, such as preferential accumulation in tumors, that are uniquely suited for chemoradiation therapy. To facilitate the clinical translation of NP chemotherapeutics in chemoradiation therapy, we conducted preclinical evaluation of Genexol-PM, the only clinically approved NP chemotherapeutic with a controlled drug ...[more]

PMID: 23708084

Similar Datasets

Project description:PurposeThis study aimed to assess the effect of nanoparticle albumin-bound paclitaxel (nab-PTX) chemotherapy regimens in elderly patients (≥70 years old) with advanced squamous non-small-cell lung cancer (NSCLC).Patients and methodsThe clinical records of elderly patients aged ≥70 years with advanced squamous NSCLC were reviewed retrospectively. All of these patients received nab-PTX, with or without combination of chemotherapy in Shandong Cancer Hospital and Institute between 1 July 2012 and 30 June 2017. We analyzed the toxicity profiles, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR).ResultsTotally, 52 elderly patients with squamous NSCLC were included in the analysis. For all patients, the ORR was 34.6%, the DCR was 80.8%, median PFS was 5.9 months (95% confidence interval [CI]: 4.0-7.8 months), and median OS was 14.3 months (95% CI: 11.0-17.8 months). Combination with chemotherapy significantly prolonged OS (19.3 vs 11.2 months, P = .016), despite a nonsignificant improvement in PFS (7.1 vs 4.2 months, P = .060) vs monotherapy. For patients who received nab-PTX as first-line treatment, the median PFS and OS were 6.7 months and 17.2 months, respectively, and the median OS in combination therapy subgroup was significantly higher than that in monotherapy group (20.3 vs 11.2 months, P = .013). Meanwhile, the median PFS and OS of patients with nab-PTX as second- or later-line treatment were 4.4 months and 13.3 months, respectively, but no survival benefit was achieved by the combination chemotherapy when compared with single-agent chemotherapy. Hematologic toxicities were the most common adverse events (AEs), which include grade 3 or 4 neutropenia (13.7%), thrombocytopenia (4.1%), and anemia (6.8%). The main nonhematologic toxicities were peripheral sensory neuropathy (39.7%), followed by anorexia and nausea/vomiting.ConclusionIn elderly advanced squamous NSCLC patients, the treatment of nab-PTX was effective and well tolerated.

Dataset Information

Preclinical evaluation of Genexol-PM, a nanoparticle formulation of paclitaxel, as a novel radiosensitizer for the treatment of non-small cell lung cancer.

Publications

Preclinical evaluation of Genexol-PM, a nanoparticle formulation of paclitaxel, as a novel radiosensitizer for the treatment of non-small cell lung cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets