Paclitaxel docosahexaenoic acid

Wolff AC, Donehower RC, Carducci MK, Carducci MA, Brahmer JR, Zabelina Y, Bradley MO, Anthony FH, Swindell CS, Witman PA, Webb NL, Baker SD. Phase I study of docosahexaenoic acid-paclitaxel a taxane-fatty acid conjugate with a unique pharmacology and toxicity profile. Clin Cancer Res 2003 9(10 Pt 1) 3589-97. 

Bedikian AY, Deconti RC, Conry R, Agarwala S, Papadopoulos N, Kim KB, Ernstoff M. Phase 3 study of docosahexaenoic acid-paclitaxel versus dacarbazine in patients with metastatic malignant melanoma. Ann Oncol 2011 22(4) 787-93. 

Homsi J, Bedikian AY, Kim KB, Papadopoulos NE, Hwu WJ, Mahoney SL, Hwu P. Phase 2 open-label study of weekly docosahexaenoic acid-paclitaxel in cutaneous and mucosal metastatic melanoma patients. Melanoma Res 2009 19(4) 238 2. 

Fracasso PM, Picus J, Wildi JD, Goodner SA, Creekmore AN, Gao F, Govindan R, Ellis MJ, Tan BR, linette GP, Fu CJ, Pentikis HS, Zumbnm SC, Egorin MJ, Bellet RE. Phase 1 and pharmacokinetic study of weekly docosahexaenoic acid-paclitaxel, Taxoprexin, in resistant solid tumor malignancies. Cancer Chemother Pharmacol 2009 63(3) 451-8. 

DHA-paclitaxel (Taxoprexin ) 62 (Luitpold) is being evaluated in a Phase III trial for the treatment of advanced non-small cell lung cancer in combination with carboplatin,136 as well against a variety of cancers in Phase II trials. DHA-paclitaxel 62,137 139 which is the C-2 docosahexaenoic acid (DHA) ester of paclitaxel 60, was licensed by Luitpold from Protarga in 2003. Polyunsaturated fatty acids have been reported to be taken up by tumour cells at a higher rate than normal cells and, as a consequence, a polyunsaturated fatty ester such as DHA-paclitaxel 62 may be absorbed more specifically in tumour cells. In preclinical studies, DHA-paclitaxel 62 exhibited increased activity in mice xenograft models and was more stable in vivo than paclitaxel 60. However, DHA-paclitaxel 62 may still suffer from efflux problems associated with paclitaxel 60 and docetaxel resistant tumours. 

Bradley MO, Shashoua VE, Webb NL, Swindell CS (1997) Preparation of Conjugates of all-cis-docosahexaenoic Acid and Paclitaxel as Antitumor Agents. PCT Int Appl WO 97 44,336 (Chem Abstr 128 34910)... 

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