A Y Bedikian1, R C DeConti2, R Conry3, S Agarwala4, N Papadopoulos5, K B Kim5, M Ernstoff6. 1. Department of Melanoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston. Electronic address: abedikia@mdanderson.org. 2. Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa. 3. Division of Hematology & Oncology, Kirkland Clinic at Acton Road, Birmingham. 4. Department of Hematology/Oncology, St Luke's Cancer Center, Bethlehem. 5. Department of Melanoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston. 6. Department of Hematology/Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, USA.
Abstract
BACKGROUND:Docosahexaenoic acid-paclitaxel (DHA-paclitaxel, Taxoprexin(®)) is made by covalently conjugating the essential fatty acid DHA to the paclitaxel molecule. Preclinical studies of DHA-paclitaxel have demonstrated increased activity relative to paclitaxel and the potential for an improved therapeutic ratio. In the present study, the efficacy and toxicity profiles of DHA-paclitaxel were compared with those of dacarbazine. METHODS: In this study, 393 chemonaive patients with metastatic melanoma were randomly assigned to receive either DHA-paclitaxel at a starting dose of 900 mg/m(2) IV on day 1 every 3 weeks or dacarbazine at a starting dose of 1000 mg/m(2) IV on day 1 every 3 weeks. The primary end point of the study was the comparison of overall survival (OS). RESULTS: No significant difference in OS was noted between patients in the DHA-paclitaxel and dacarbazine arms. Similarly, there were no significant differences in response rate, duration of response, time to progression, and time to treatment failure between the two drugs. Safety results of the two drugs were as predicted from prior studies. Myelosuppression was more common with DHA-paclitaxel. CONCLUSIONS:DHA-paclitaxel was not superior to dacarbazine. We conclude that further studies with the drug on an every 3-week schedule in melanoma are not warranted.
RCT Entities:
BACKGROUND:Docosahexaenoic acid-paclitaxel (DHA-paclitaxel, Taxoprexin(®)) is made by covalently conjugating the essential fatty acidDHA to the paclitaxel molecule. Preclinical studies of DHA-paclitaxel have demonstrated increased activity relative to paclitaxel and the potential for an improved therapeutic ratio. In the present study, the efficacy and toxicity profiles of DHA-paclitaxel were compared with those of dacarbazine. METHODS: In this study, 393 chemonaive patients with metastatic melanoma were randomly assigned to receive either DHA-paclitaxel at a starting dose of 900 mg/m(2) IV on day 1 every 3 weeks or dacarbazine at a starting dose of 1000 mg/m(2) IV on day 1 every 3 weeks. The primary end point of the study was the comparison of overall survival (OS). RESULTS: No significant difference in OS was noted between patients in the DHA-paclitaxel and dacarbazine arms. Similarly, there were no significant differences in response rate, duration of response, time to progression, and time to treatment failure between the two drugs. Safety results of the two drugs were as predicted from prior studies. Myelosuppression was more common with DHA-paclitaxel. CONCLUSIONS:DHA-paclitaxel was not superior to dacarbazine. We conclude that further studies with the drug on an every 3-week schedule in melanoma are not warranted.
Authors: Poulam M Patel; Stefan Suciu; Laurent Mortier; Wim H Kruit; Caroline Robert; Dirk Schadendorf; Uwe Trefzer; Cornelis J A Punt; Reinhard Dummer; Neville Davidson; Juergen Becker; Robert Conry; John A Thompson; Wen-Jen Hwu; Kristel Engelen; Sanjiv S Agarwala; Ulrich Keilholz; Alexander M M Eggermont; Alain Spatz Journal: Eur J Cancer Date: 2011-05-18 Impact factor: 9.162
Authors: Miranda Payne; Paul Ellis; David Dunlop; Malcolm Ranson; Sarah Danson; Lee Schacter; Denis Talbot Journal: J Thorac Oncol Date: 2006-11 Impact factor: 15.609
Authors: M B Atkins; M T Lotze; J P Dutcher; R I Fisher; G Weiss; K Margolin; J Abrams; M Sznol; D Parkinson; M Hawkins; C Paradise; L Kunkel; S A Rosenberg Journal: J Clin Oncol Date: 1999-07 Impact factor: 44.544
Authors: C M Balch; A C Buzaid; S J Soong; M B Atkins; N Cascinelli; D G Coit; I D Fleming; J E Gershenwald; A Houghton; J M Kirkwood; K M McMasters; M F Mihm; D L Morton; D S Reintgen; M I Ross; A Sober; J A Thompson; J F Thompson Journal: J Clin Oncol Date: 2001-08-15 Impact factor: 44.544
Authors: Agop Y Bedikian; Carl Plager; Nicholas Papadopoulos; Omar Eton; Julie Ellerhorst; Theresa Smith Journal: Melanoma Res Date: 2004-02 Impact factor: 3.599
Authors: Robert J Jones; Robert E Hawkins; Martin M Eatock; David R Ferry; Ferry A L M Eskens; HansJochen Wilke; T R Jeffry Evans Journal: Cancer Chemother Pharmacol Date: 2007-04-18 Impact factor: 3.333
Authors: Jade Homsi; Agop Y Bedikian; Kevin B Kim; Nicholas E Papadopoulos; Wen-Jen Hwu; Sandy L Mahoney; Patrick Hwu Journal: Melanoma Res Date: 2009-08 Impact factor: 3.599
Authors: Aditya G Kohli; Paul H Kierstead; Vincent J Venditto; Colin L Walsh; Francis C Szoka Journal: J Control Release Date: 2014-05-06 Impact factor: 9.776
Authors: Cong Luo; Jin Sun; Dan Liu; Bingjun Sun; Lei Miao; Sara Musetti; Jing Li; Xiaopeng Han; Yuqian Du; Lin Li; Leaf Huang; Zhonggui He Journal: Nano Lett Date: 2016-08-08 Impact factor: 11.189
Authors: Cong Luo; Jin Sun; Bingjun Sun; Dan Liu; Lei Miao; Tyler Jay Goodwin; Leaf Huang; Zhonggui He Journal: Small Date: 2016-09-30 Impact factor: 13.281
Authors: E M Hersh; M Del Vecchio; M P Brown; R Kefford; C Loquai; A Testori; S Bhatia; R Gutzmer; R Conry; A Haydon; C Robert; S Ernst; J Homsi; J J Grob; K Kendra; S S Agarwala; M Li; A Clawson; C Brachmann; M Karnoub; I Elias; M F Renschler; A Hauschild Journal: Ann Oncol Date: 2015-09-26 Impact factor: 32.976