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Polyethylene glycol microspheres loaded with irinotecan for arterially directed embolic therapy of metastatic liver cancer.

ABSTRACT: AIM:To study tumor response, and tolerability of arterially directed embolic therapy (ADET) with polyethylene glycol embolics loaded with irinotecan for the treatment of colorectal cancer liver metastases (CRC-LM). Secondary objectives were to monitor quality of life, time to progression and survival of patients. METHODS:Patients were included in the study if they were affected by CRC-LM, refractory to systemic chemotherapy, treated with ADET using polyethylene glycol embolics, and had liver involvement < 50%. Tumor response, performance status (PS), tumor marker antigens, and quality of life (QoL) were monitored at 1, 3 and 6 mo after ADET. QoL was assessed with the Palliative Performance Scale (PPS). RESULTS:We treated 50 consecutive CRC-LM patients with ADET using polyethylene glycol embolics. Their tumor response one month after ADET was: 28% of complete response (CR), 48% of partial response (PR), 8% stable disease (SD), and 16% of progression. Tumor response 3 mo after ADET was CR 24%, PR 38%, SD 19% and progression disease (PD) 19%. Tumor response 6 mo after ADET was CR 18%, PR 44%, SD 21% and PD 18%. QoL was 90% PPS at each time point. Median time to progression for patients who progressed was 2.5 mo (range 0.8-6). Median follow-up was 14 mo (0.8-25 range). ADETs were performed with no complications. Observed side effects (mild or moderate intensity) were: Pain in 32% of patients, increase of transaminase levels in 20% and fever in 14%, whereas 30% of patients did not complain any adverse event. CONCLUSION:The treatment of unresectable CRC-LM with ADET using polyethylene glycol microspheres loaded with irinotecan was effective in tumor response and resulted in mild toxicity, and good QoL.

SUBMITTER: Fiorentini G

PROVIDER: S-EPMC5605338 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Polyethylene glycol microspheres loaded with irinotecan for arterially directed embolic therapy of metastatic liver cancer.

Fiorentini Giammaria G Carandina Riccardo R Sarti Donatella D Nardella Michele M Zoras Odysseas O Guadagni Stefano S Inchingolo Riccardo R Nestola Massimiliano M Felicioli Alessandro A Barnes Navarro Daniel D Munoz Gomez Fernando F Aliberti Camillo C

World journal of gastrointestinal oncology 20170901 9

<h4>Aim</h4>To study tumor response, and tolerability of arterially directed embolic therapy (ADET) with polyethylene glycol embolics loaded with irinotecan for the treatment of colorectal cancer liver metastases (CRC-LM). Secondary objectives were to monitor quality of life, time to progression and survival of patients.<h4>Methods</h4>Patients were included in the study if they were affected by CRC-LM, refractory to systemic chemotherapy, treated with ADET using polyethylene glycol embolics, an ...[more]

PMID: 28979720

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Project description:BackgroundColorectal cancer is one of the prominent leading causes of fatality worldwide. Despite recent advancements within the field of cancer therapy, the cure rates and long-term survivals of patients suffering from colorectal cancer have changed little. The application of conventional chemotherapeutic agents like doxorubicin is limited by some drawbacks such as cardiotoxicity and hematotoxicity. Therefore, nanotechnology has been exploited as a promising solution to address these problems. In this study, we synthesized and compared the anticancer efficacy of doxorubicin-loaded liposomes that were surface engineered with the 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-matrix metalloproteinase-2 (MMP-2) cleavable peptide-polyethylene glycol (PEG) conjugate. The peptide linker was used to cleave in response to the upregulated MMP-2 in the tumor microenvironment, thus exposing a positive charge via PEG-deshielding and enhancing liposomal uptake by tumor cells/vasculature. Liposomal formulations were characterized in terms of size, surface charge and morphology, drug loading, release properties, cell binding and uptake, and cytotoxicity.ResultsThe formulations had particle sizes of ~ 100-170 nm, narrow distribution (PDI ˂ 0.2), and various surface charges (- 10.2 mV to + 17.6 mV). MMP-2 overexpression was shown in several cancer cell lines (C26, 4T1, and B16F10) as compared to the normal NIH-3T3 fibroblast cells by gelatin zymography and qRT-PCR. In vitro results demonstrated enhanced antitumor efficacy of the PEG-cleavable cationic liposomes (CLs) as compared to the commercial Caelyx® (up to fivefold) and the chick chorioallantoic membrane assay showed their great antiangiogenesis potential to target and suppress tumor neovascularization. The pharmacokinetics and efficacy studies also indicated higher tumor accumulation and extended survival rates in C26 tumor-bearing mice treated with the MMP-2 cleavable CLs as compared to the non-cleavable CLs with no remarkable sign of toxicity in healthy tissues.ConclusionAltogether, the MMP-2-cleavable CLs have great potency to improve tumor-targeted drug delivery and cellular/tumor-vasculature uptake which merits further investigation.Supplementary informationThe online version contains supplementary material available at 10.1186/s12645-023-00169-8.

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Polyethylene glycol microspheres loaded with irinotecan for arterially directed embolic therapy of metastatic liver cancer.

Publications

Polyethylene glycol microspheres loaded with irinotecan for arterially directed embolic therapy of metastatic liver cancer.

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