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
4369 - Biomarker testing of lung cancer in Spain
Presenter: Delvys Rodriguez Abreu
Session: Poster Display session 1
Resources:
Abstract
603 - Mendelian Randomization Study of Alzheimer's Disease and Lung Cancer
Presenter: Huaqiang Zhou
Session: Poster Display session 1
Resources:
Abstract
4462 - Spanish registry of thoracic tumors (TTR): Interim analyses of comorbidities, risk associations, personal and family history of cancer
Presenter: Rafael Lopez Castro
Session: Poster Display session 1
Resources:
Abstract
3957 - Pleural effusion TGF-beta is highly diagnostic and prognostic in malignant pleural mesothelioma
Presenter: Paul Stockhammer
Session: Poster Display session 1
Resources:
Abstract
3583 - Immune microenvironment modulation by p14/ARF in Malignant Pleural Mesothelioma
Presenter: Giulia Pasello
Session: Poster Display session 1
Resources:
Abstract
4255 - Tumor Treating Fields plus chemotherapy for first-line malignant pleural mesothelioma (MPM): radiological responses in the STELLAR trial
Presenter: Federica Grosso
Session: Poster Display session 1
Resources:
Abstract
1803 - Effects of Tumor Treating Fields (TTFields; 150 kHz) and Cisplatin or Pemetrexed Combination Therapy on Mesothelioma cells In Vitro and In Vivo
Presenter: Mijal Munster
Session: Poster Display session 1
Resources:
Abstract
2660 - Real world use of systemic therapy in elderly patients with malignant pleural mesothelioma (MPM)
Presenter: Susana Cedres
Session: Poster Display session 1
Resources:
Abstract
3150 - Pemetrexed/Cisplatin versus Gemcitabine/Cisplatin as first-line treatment for Egyptian patients with malignant pleural mesothelioma
Presenter: Mohamed Alorabi
Session: Poster Display session 1
Resources:
Abstract
4319 - Accuracy of pathologic evaluation for thymic epithelial tumors in an Italian reference Centre
Presenter: Giulia Galli
Session: Poster Display session 1
Resources:
Abstract