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 |
|---|---|---|---|---|
| PD17060 | Human Rhabdomyo- sarcoma (RMS) cell line (SJCRH30) [1.5 × 106/mouse] | 200 | Saline TLC178 (5 mg/kg) VNB solution (5 mg/kg) | TLC178 and VNB were injected at a 4-day interval for three doses. |
| PD17069 | Human RMS cell line (SJCRH30) [4 × 106/mouse] | 150 | Saline 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. |
| PD17008 | Human fibrosarcoma cell line (HT1080) [2.2 × 106/mouse] | 390 | D5W TLC178 (5 mg/kg) Doxorubicin (3.4 mg/kg) | TLC178 and doxorubicin were injected at a 4-day interval for two doses. |
| PK17066 | Human RMS cell line (SJCRH30) [2.3 × 106/mouse] | 150 to 400 | TLC178 (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.
Resources from the same session
1757 - Development of chimeric antigenic receptor (CAR) against VEGFR2 for solid tumor treatment
Presenter: Li-Shuang Ai
Session: Poster Display session 1
Resources:
Abstract
4156 - Triple blockade of EGFR, MEK and PD-L1 as effective antitumor treatment in PD-L1 overexpressing, MEK inhibitor resistant colon cancer cells.
Presenter: Nunzia Matrone
Session: Poster Display session 1
Resources:
Abstract
2949 - EGFR-mediated PD-L1 upregulation in HER2+ breast cancer (BC) cell line models
Presenter: Nicola Gaynor
Session: Poster Display session 1
Resources:
Abstract
4270 - The impact of cortisol on immune cells and its effect on cancer-immune cells co-culture in a 3D spheroid of ovarian cancer
Presenter: Maysa Al-natsheh
Session: Poster Display session 1
Resources:
Abstract
1568 - Application of sonoporation to increase anticancer drug efficacy in 2D and 3D NSCLC cell cultures
Presenter: Vilma Petrikaite
Session: Poster Display session 1
Resources:
Abstract
5400 - Tr1-like cells in human peripheral blood are part of the T effector memory pool and are preferentially stimulated via CD55
Presenter: Iniobong Charles
Session: Poster Display session 1
Resources:
Abstract
5817 - Functional analysis of tumor infiltrating lymphocytes in triple negative breast cancer focusing on granzyme B
Presenter: Hitomi Kawaji
Session: Poster Display session 1
Resources:
Abstract
2287 - Aberrant glycolysis associates with inflammatory tumor microenvironment and promotes metastasis in triple-negative breast cancer
Presenter: Chengwei Lin
Session: Poster Display session 1
Resources:
Abstract
735 - Anti-cancer effects of differentiation-inducing factor-1 in triple negative breast cancer.
Presenter: Fumi Tetsuo
Session: Poster Display session 1
Resources:
Abstract
2105 - The Inhibitory Effect in Oral Squamous Cell Carcinoma Cells by Knocking down Matrix Metalloproteinase 9
Presenter: Xinyan Zhang
Session: Poster Display session 1
Resources:
Abstract