ABRAXANE in Radiation Therapy

1. ABRAXANE ® Newer Dimensions in Radiation Therapy Dr. V. Lokesh M.D Associate Professor Dept of Radiation Oncology Kidwai Memorial Institute of Oncology

4. TAXANES: Review

12. Cremophor paclitaxel : Large Micelles Observed in Plasma Control plasma Plasma + Taxol Large Micelle Hamad and Moghimi, Expert Opin. Drug Deliv. (2008) 5 (2):205-219

20. Nab in size perspective Human hair = 100,000 nm Albumin = 5 nm Hemoglobin = 6.5 nm Proteins Red Blood Cells RBC = 8000 nm Nanoparticles Nab-technology ~100nm

21. Human albumin hydrophobic drug Size : ~ 50-150 nm

22. Abraxane Solvent based Paclitaxel 0 hr 0 hr 24 hr Microscopic assessment at 5 mg/mL, 40  C: De et al., AACR 2008 Unstable: aggregate ↓ drug delivery

25. Abraxane vs. Taxol Phase 3 Clinical Trial Journal Clin Oncology, 2005;23.

27. ABRAXANE & RADIATION THERAPY

35. Paclitaxel PK for Abraxane are Linear (1): Kearns, C. M., Pharmacotherapy, 1997 (2): Taxol Package insert (3): Mross et al, Cancer Chemother Pharm 2000 Taxol Abraxane Source: Abraxane NDA

36. Cremophor Alters the Distribution Phase PK of Paclitaxel Source: Abraxane NDA and Sparreboom et al., 2005, CCR Terminal phase-metabolism/excretion (8-72 hr) Initial distribution phase (0-8 hr)

37. Thank You