Phase 3 study of docosahexaenoic acid-paclitaxel versus dacarbazine in patients with metastatic malignant melanoma.
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.
Bedikian
A Y
AY
Department of Melanoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston. Electronic address: abedikia@mdanderson.org.
DeConti
R C
RC
Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa.
Conry
R
R
Division of Hematology & Oncology, Kirkland Clinic at Acton Road, Birmingham.
Agarwala
S
S
Department of Hematology/Oncology, St Luke's Cancer Center, Bethlehem.
Papadopoulos
N
N
Department of Melanoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston.
Kim
K B
KB
Department of Melanoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston.
Ernstoff
M
M
Department of Hematology/Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, USA.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003606:Dacarbazine / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D003606:Dacarbazine; C528070:docosahexaenoyl-paclitaxel; D017239:Paclitaxel