2036 Background: Docosahexaenoic acid-paclitaxel (DHAP) is a covalent conjugate of paclitaxel and the essential fatty acid, docosahexaenoic acid. Preclinical studies have demonstrated increased activity relative to paclitaxel with the potential for an improved therapeutic ratio. We performed a phase 1 and pharmacokinetics (PK) study of DHAP in patients with resistant solid tumor malignancies. Methods: Patients were treated with DHAP administered by 2-hour intravenous infusion weekly for three out of four weeks. Dose escalation started at DHAP 200 mg/m2 and was increased by 100 mg/m2 per dose level ending at 600 mg/m2. Blood samples for PK of DHAP and paclitaxel derived from DHAP were collected in cycle 1 at 0 (prior to the start of the infusion), 2 (prior to the end of the infusion), 3, 4, 9, 26 hours and just prior to the next weekly treatment on days 8, 15 and 29. Results: Twenty-one patients enrolled and received 39 cycles of treatment (mean = 2). Three patients received DHAP at 200 mg/m2 (dose level 1), four at 300 mg/m2 (dose level 2), three at 400 mg/m2 (dose level 3) and 500 mg/m2 (dose level 4) each, and eight at 600 mg/m2 (dose level 5). In cycle 1, grade 2/3 neutropenia resulted in treatment delays for 8 patients, 6 of whom received treatment at dose level 4 and 5. Two of the 8 patients, treated with DHAP 600 mg/m2, went on to experience grade 4 neutropenia lasting < five days on later cycles. Only one patient had grade 2 sensory neuropathy, which occurred after 3 cycles of treatment. Preliminary PK analyses on all patients demonstrated that there is not a substantial accumulation of DHAP or paclitaxel with weekly treatment. Detailed PK analyses will be presented. Eighteen of the 21 patients were evaluable for response. Three patients, one each with esophageal and lung carcinoma and melanoma, had stable disease for 11, 16, and 17 weeks, respectively. Conclusions: DHAP administered weekly at 600 mg/m2 was well-tolerated and the maximum dose administered in this study. The slow release of paclitaxel from DHAP and the weekly schedule approximates continuous infusion paclitaxel which should be more active than every 3 week or weekly taxanes. Further studies with DHAP in non-small cell lung carcinoma and melanoma are on-going. [Table: see text]