40P - Antitumoral effect and reduced systemic toxicity in mice after intra-tumoral injection of an in vivo solidifying calcium sulfate formulation with d...

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Lung and other Thoracic Tumours
Translational Research
Presenter Martin Sandelin
Citation Annals of Oncology (2017) 28 (suppl_2): ii9-ii13. 10.1093/annonc/mdx089
Authors M. Sandelin1, S. Grudén2, V. Rasanen1, P. Micke1, M. Hedeland3, N. Axén2, M. Jeansson1
  • 1Department Of Immunology, Genetics And Pathology, Akademiska sjukhuset,Uppsala, SE-751 85 - Uppsala/SE
  • 2LIDDS AB, SE-754 50 - Uppsala/SE
  • 3Department Of Chemistry, Environment And Feed Hygiene, National Veterinary Institute (SVA), SE-751 89 - Uppsala/SE

Abstract

Background

Docetaxel is a cytostatic agent approved for treatment of non-small cell lung cancer as well as other cancers. Its effectiveness in clinical practice is associated with a variety of acute and long term side effects. To reduce the systemic side effects, a local slow-release depot formulation based on calcium sulfate with docetaxel for intra-tumoral administration was developed.

Methods

Two formulations with a twofold difference in docetaxel drug load (corresponding to 12.5 and 25.0 mg/kg body weight) were manufactured with the calcium sulfate based NanoZolid™ technology. The formulations were injected intra-tumorally as a paste which solidified within the tumor. The effects of the two local depot formulations were tested in female mice (n = 60) inoculated with subcutaneous Lewis lung carcinoma cells. The slow-release depots were compared to systemic intraperitoneal injections of docetaxel (25.0 mg/kg) and a calcium sulfate placebo formulation. Tumor volumes were measured and systemic side effects were evaluated using body weight and cell counts from whole blood as well as plasma concentrations. In addition, a histological evaluation was performed.

Results

Both docetaxel formulations showed a significantly higher antitumor efficacy compared to placebo, which was comparable to that of systemic administration of docetaxel. Moreover, the intra-tumoral depot formulations with docetaxel showed reduced systemic toxicity compared to systemic treatment, including less weight loss and no decrease in blood cell counts. The extracellular deposits of calcium sulfate, observed in all groups with intra-tumoral injections, did not lead to significant inflammatory changes.

Conclusions

It was shown that intra-tumoral slow-release depots of calcium sulfate with docetaxel were well tolerated and released docetaxel at amounts sufficient for satisfactory local antitumor effect and for a low level plasma detection. The use of such depots can be an alternative to intravenous injection as an efficient antitumoral treatment with reduced systemic toxicity.

Clinical trial identification

Legal entity responsible for the study

Uppsala University, Department of Immunology, Genetics and Pathology, Marie Jeansson

Funding

This study was supported by an IGP Young Investigator grant (MJ), the Swedish Research Council (521-2012-865, MJ), Åke Wiberg Foundation (738866289, MJ), Magnus Bergvalls Foundation (24942-1-2013, 2014-00055, MJ), and Ture Stenholms Foundation for Surgical Research (MS)

Disclosure

S. Grudén: Consultant for LIDDS AB. N. Axén: Consultant for LIDDS AB and have equity interests in LIDDS AB. All other authors have declared no conflicts of interest.