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
5553 - Cytokine genetic variations and worse quality of life among family caregivers of head and neck cancer patients in palliative care
Presenter: Daniel Pequeno
Session: Poster Display session 1
Resources:
Abstract
4321 - Health-related quality of life of advanced melanoma survivors treated with CTLA-4 immune checkpoint inhibition: a matched cohort study
Presenter: Annelies Boekhout
Session: Poster Display session 1
Resources:
Abstract
779 - Capecitabine vs Cisplatin along with concurrent radiotherapy in the treatment of inoperable lower esophageal cancers focusing on TWISTT score and QOL
Presenter: Goutham Anugu
Session: Poster Display session 1
Resources:
Abstract
5914 - Cancer, Mental Health and End Life Simulation (CAMhELS): A novel effectiveness evaluation.
Presenter: Asanga Fernando
Session: Poster Display session 1
Resources:
Abstract
2597 - Cancer patients’ expectations and understanding about their disease
Presenter: Mónica Pinho
Session: Poster Display session 1
Resources:
Abstract
5187 - Impact of patients’ death on oncologists and coping strategies: An online survey
Presenter: Soumaya Labidi
Session: Poster Display session 1
Resources:
Abstract
4579 - Clinical benefit from late lines of therapy offered to patients treated in a tertiary referral centre
Presenter: Andrea Sbrana
Session: Poster Display session 1
Resources:
Abstract
5058 - Preparedness for caregiving in caregivers of cancer patients
Presenter: Hatice Yakar
Session: Poster Display session 1
Resources:
Abstract
5917 - Oncologic Emergency Medicine in the real world: A survey and proposal for improvement
Presenter: Carintia Dorta Pérez
Session: Poster Display session 1
Resources:
Abstract
4077 - The Reality of Critical Cancer Patients in a Polyvalent Intensive Care Unit
Presenter: Tiago Filipe Da Cruz Tomas
Session: Poster Display session 1
Resources:
Abstract