DHA-paclitaxel

DHA-paclitaxel Oncology Tubulin binding Phase III Luifr)oId 665, 666... 

Jones RJ, Hawkins RE, Eatock MM, Ferry DR, Eskens FA, Wilke H, Evans TR. (2008) A phase II openlabel study of DHA-paclitaxel (Taxoprexin) by 2-h intravenous infusion in previously untreated patients with locally advanced or metastatic gastric or oesophageal adenocarcinoma. Cancer Chemother Pharmacol 61 435 41. 

DHA-paclitaxel 62 semi-synthetic NP paclitaxel 60 (plant, 1971)131 oncology... 

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. 

Paclitaxel is poorly water-soluble and so is conventionally administered via a poly-oxyethylated castor oil derivative, Cremo-phor EL, which is a micelle-forming vehicle. This has now been found to affect the pharmacokinetics of paclitaxel, as well as its adverse reactions, as detailed below. More recently, two new formulations have been developed albumin-bound paclitaxel (marketed as Abraxane ) and docosahexae-noic acid paclitaxel (DHA paclitaxel, marketed as Taxoprexin ). Both have different pharmacokinetics and adverse reactions from conventional paclitaxel, as discussed separately below. 

DHA paclitaxel has been tested in a number of solid tumors so far in phase I and phase II trials and has shown some efficacy... 

In phase I and phase II studies DHA paclitaxel has been administered with glucocorticoid and antihistamine premedication [104, 1085]. However, there have been reports of hypersensitivity reactions despite this [104]. A significant difference compared with conventional paclitaxel is the relatively small incidence of peripheral neuropathy and no reports of alopecia so far [102f 106 ]. 

Payne M, Ellis P, Dunlop D, Ranson M, Danson S, Schacter L, Talbot D. DHA-paclitaxel (Taxoprexin) as first-line treatment in patients with stage IIIB or IV non-small cell lung cancer report of... 

Bradley MO, Swindell CS, Anthony FH, Witman PA, Devanesan P, Webb NL, Baker SD, Wolff AC, Donehower RC (2001) Tumor Targeting by Conjugation of DHA to Paclitaxel. J Controlled Release 74 233... 

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