docosahexaenoyl-paclitaxel and Melanoma

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.. 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).. 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.. 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.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Dacarbazine; Disease Progression; Disease-Free Survival; Female; Humans; Male; Melanoma; Middle Aged; Neoplasm Metastasis; Paclitaxel

Docosahexaenoic acid (DHA)-paclitaxel is a taxane with a unique pharmacokinetic profile. We investigated the safety and response rate of DHA-paclitaxel weekly in patients with metastatic uveal melanoma. Chemotherapy-naive and previously treated patients were eligible for this open-label phase II study. DHA-paclitaxel (500 mg/m²/week) was administered by a 1-hour intravenous infusion for five consecutive weeks in a 6-weeks cycle. Response was assessed using the Response Evaluation Criteria in Solid Tumors every 6 weeks. Twenty-two patients were enrolled. The patients' median age was 56 years (range: 33-79 years). Nine patients had a systemic therapy for metastatic disease earlier. The median number of treatment cycles was 1 (range 1-7 cycles). One chemonaive patient with liver metastases had partial response lasting for 5 months. Seven patients (32%) had stable disease with a median duration of 3 months (range: 3-7 months). The median overall survival was 9.8 months. Neutropenia (23%) and musculoskeletal pain (10%) were the most common grade 3 and grade 4 toxicities. As a single-agent therapy, DHA-paclitaxel is safe and well-tolerated in metastatic uveal melanoma patients. Its efficacy in this disease is limited with 32% of patients achieving stable disease. Further evaluation of DHA-paclitaxel in combination with other chemotherapeutic agents and/or targeted agents may improve its antitumor activity.

Topics: Adult; Aged; Antineoplastic Agents; Drug Administration Schedule; Female; Humans; Male; Melanoma; Middle Aged; Neoplasm Metastasis; Paclitaxel; Survival Rate; Uveal Neoplasms

Docosahexaenoic acid (DHA)-paclitaxel has a unique pharmacokinetic profile that allows high concentrations of paclitaxel to be delivered to melanoma cells for prolonged periods compared with paclitaxel. We investigated the response rate and safety of weekly DHA-paclitaxel in metastatic melanoma patients. We enrolled chemotherapy-naive patients with metastatic nonchoroidal melanoma using the two-stage Fleming design. At least one response was needed in the first stage to proceed to the second stage. DHA-paclitaxel (500 mg/m/week by 1-h intravenous infusion) was administered for 5 weeks every 6-week cycle until disease progression, intolerable toxicity, or treatment refusal. Response and toxicity were assessed every 6 weeks and weekly, respectively. Thirty patients were enrolled. The patients' median age was 67 years (range: 29-86 years). The median number of treatment cycles was 2 (range: 1-6 cycles). Three patients (10%) had partial responses; one lasted 4 months, and two lasted 5.6 months. Fifteen patients (50%) had stable disease with a median duration of 2.8 months (range: 2.6-8.9 months). The median survival was 14.8 months. Neutropenia (10%) and musculoskeletal pain (10%) were the most common grade 3 and 4 toxicities, and fatigue (73%), skin rash (70%), and diarrhea (60%) were the most common side effects. As a single-agent therapy, DHA-paclitaxel was well tolerated in metastatic melanoma patients. Its efficacy as a first-line therapy for metastatic melanoma does not exceed that seen with other single-agent chemotherapies such as dacarbazine. Further evaluation of DHA-paclitaxel in combination with other chemotherapy or targeted agents could be considered.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Diarrhea; Exanthema; Fatigue; Female; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Male; Melanoma; Middle Aged; Neutropenia; Paclitaxel; Pain; Skin Neoplasms; Survival Rate; Tumor Burden