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Poster Display session 1

1844 - In Vivo Efficacy and Enhanced Tumor Accumulation of Liposomal Vinorelbine (TLC178) in Human Sarcoma Xenograft Mice Model

Date

28 Sep 2019

Session

Poster Display session 1

Topics

Tumour Site

Sarcoma

Presenters

Wan-ni Yu

Citation

Annals of Oncology (2019) 30 (suppl_5): v683-v709. 10.1093/annonc/mdz283

Authors

W. Yu1, J. Tang1, Y. Tsai2, H. Wang2

Author affiliations

  • 1 Non-clinical Department, Taiwan Liposome Company, 115 - Taipei/TW
  • 2 Pharmacokinetic Department, Taiwan Liposome Company, 115 - Taipei/TW
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Resources

Abstract 1844

Background

Vinorelbine (VNB) is a member of vinca alkaloid medications and approved for the treatment of non-small cell lung cancer as well as off-label use for metastatic breast cancer over 20 years based upon FDA-approved indication. Several studies have suggested the potential of VNB in treating sarcomas. Liposomal VNB (TLC178) is a novel sustained release liposomal formulation. In the presented studies, TLC178 resulted in enhanced tumor accumulation and greater anti-tumor efficacy than non-liposomal VNB.

Methods

Mice were subcutaneously inoculated with human sarcoma cell lines (1.5∼4 × 106/mouse) at the dorsal-lateral flank. Treatment was commenced once tumor size reached 150 to 400 mm3 in average. Mice were intravenously (i.v.) injected with test articles by groups.Table:

1722P

Study #Cell Type [Cell Density]Initial Tumor Size (mm3)Treatment Group (Dosage)Dosing Regimen
PD17060Human Rhabdomyo- sarcoma (RMS) cell line (SJCRH30) [1.5 × 106/mouse]200Saline TLC178 (5 mg/kg) VNB solution (5 mg/kg)TLC178 and VNB were injected at a 4-day interval for three doses.
PD17069Human RMS cell line (SJCRH30) [4 × 106/mouse]150Saline TLC178 (7.5 mg/kg) VNB solution (10 mg/kg) + cyclophosphamide (CTX) (19.8 mg/kg)TLC178 and VNB were injected once weekly for two doses while CTX was administrated at 19.8 mg/kg on day 0, 7 and 50 mg/kg on day 8.
PD17008Human fibrosarcoma cell line (HT1080) [2.2 × 106/mouse]390D5W TLC178 (5 mg/kg) Doxorubicin (3.4 mg/kg)TLC178 and doxorubicin were injected at a 4-day interval for two doses.
PK17066Human RMS cell line (SJCRH30) [2.3 × 106/mouse]150 to 400TLC178 (5 mg/kg) TLC178 (10 mg/kg) VNB solution (10 mg/kg)Single injection

*Tumor size was monitored with digital caliper during the study. * Plasma and tumors were collected to determine VNB concentration in bio-distribution study. * Saline or D5W (Dextrose 5% in Water) was used as the control group according to the study design. * VNB solution is vinorelbine injectable solution

Results

In efficacy studies (Study #PD17060, #PD17069 and #PD17008), TLC178 not only showed better inhibitory effect than that of VNB alone and VNB+CTX treatments in the SJCRH30 RMS xenograft model, but also remarkably suppressed HT1080 human fibrosarcoma compared with doxorubicin, an approved drug for treatment of sarcomas. In a biodistribution study (Study #PK17066), TLC178 yielded larger systemic exposure of total VNB (comprising liposome-encapsulated and unencapsulated VNB), higher local concentration and longer elimination half-life in tumor compared to VNB.

Conclusions

TLC178 demonstrated improved in vivo systemic VNB PK profile and tumor distribution, which resulted in superior anti-cancer efficacy compared to traditional VNB treatment. Therefore, TLC178 may have potential as a single or combination treatment for sarcomas with decreased dosage and/or frequency, reduced toxicity, and enhanced efficacy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Taiwan Liposome Company, Ltd.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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