Safety and efficacy of DHA-paclitaxel (TXP) in non-small cell lung cancer (NSCLC).
Schacter L., Talbot D., Ellis P., Dunlop D., Thatcher N.
7111 Background: DHA-paclitaxel (Taxoprexin [TXP]) is a covalent conjugate of paclitaxel and docosahexanoic acid that has greater tumour specificity in pre-clinical models than paclitaxel. It accumulates in tumour tissue where it is cleaved to paclitaxel. The objective of this multi-centre study was to determine the efficacy and tolerability of TXP as first line therapy in advanced NSCLC. METHODS: A total of 44 patients (pts) [29 male, 15 female, median age 61y (range 39-74) PS 0 (11pts) PS 1 (33pts)] with pathologically confirmed stage IIIB or IV NSCLC and no previous cytotoxic treatment were enrolled. Pts were required to have adequate renal, hepatic and bone marrow function and have measurable disease. TXP was administered iv over 2 hours q21 days at one of two doses, 900 mg/m(2) (31pts) and 1100 mg/m(2) (13pts). Due to excess toxicity, including one toxic death, the starting dose was reduced to 900 mg/m(2). As of November 2003 four pts remain on follow-up. RESULTS: Twenty-eight courses (mean 2.1) were administered in the 1100 mg/m(2) cohort and 109 courses (mean 3.5) for 900 mg/m(2). Neutropenia was the primary toxicity and was dose related; 21 of 31 (68%) of patients treated at 900 mg/m(2) had grade 3 or 4 neutropenia while 10 of 13 (77%) at 1100 mg/m(2) had these grades of neutropenia. No grade 3 or 4 nausea /or vomiting, stomatitis or neuropathies were observed. Forty patients were evaluable for response: 900 mg/m(2) PR 2/30 (6.7%), SD 13/30 (43%); 1100 mg/m(2) PR 0/10 (0%), SD 3/10 (30%). Survival (see table) at the 900 mg/m(2) dose level was comparable to that seen with standard platinum based combination chemotherapy. (Supported by American Regent.) [Figure: see text] [Table: see text].