Phase 1-2a dose ranging study of TLK286 (a novel glutathione analog) in combination with docetaxel in platinum-resistant non-small cell lung cancer (NSCLC). V. Papadimitrakopoulou, P. Boasberg, R. Figlin, R. Zinner, G. Blumenschein, L. King, M. Truong, K. Patel, G. L. Brown, N. Hanna; M. D. Anderson Cancer Center, Houston, TX; Cancer Institute Medical Group, Los Angeles, CA; University of California Los Angeles, Los Angeles, CA; Telik, Inc, Palo Alto, CA; Indiana University Cancer Center, Indianapolis, IN Abstract: Background: TLK286 (Telcyta) is a novel glutathione analog prodrug activated by GST P1-1, which is overexpressed in NSCLC, releasing two electrophilic fragments that induce apoptosis. TLK286 has demonstrated significant single agent activity by RECIST in two Phase 2 NSCLC trials. In preclinical models, TLK286 is not cross resistant to docetaxel and shows synergistic inhibition in MCF-7 cells. Methods: The objectives were to determine the MTD of the TLK286/docetaxel combination and the objective response rate (ORR) by RECIST. NSCLC patients (pts) who had failed prior platinum-based therapy were treated with TLK286 at 500, 750 or 960 mg/m2 and docetaxel at 75 mg/m2 every 3 weeks until tumor progression or unacceptable toxicity. Results: At interim analysis, 30 pts (16 M, 14 F), median age 65 (range 46-80), median ECOG performance status 1, median prior regimens 1.5 (range 1-3) have received 103+ cycles (mean 3.4 cycles/pt, range 1-11). Pts failed prior therapies with: platinum (100%), paclitaxel (70%), pemetrexed (17%), EGFR inhibitors (33%), gemcitabine (10%), others (20%). The MTD of 960/75 mg/m2 of TLK286/docetaxel was well tolerated without dose limiting toxicities. Most common adverse events related to the TLK286/docetaxel combination were: Grade 1-2 fatigue, nausea, vomiting, anorexia, alopecia. Grade 3-4 neutropenia (15%), leukopenia (10%) and fatigue (15%) was seen. Febrile neutropenia occurred as expected with docetaxel in 7%. No cumulative toxicity has been seen. Six PRs (ORR=25%) and 11 SDs (DSR=71%) of 24 evaluable pts at TLK286/docetaxel dose of 960/75 mg/m2 were reported. Conclusions: TLK286/docetaxel combination has been well tolerated and is an active regimen in platinum resistant NSCLC. The recommended TLK286/docetaxel combination dose is 960/75 mg/m2 for future studies in NSCLC, ovarian and breast cancer. Abstract No: 7140 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.