Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : TITAN PHARMACEUTICAL (TTP) -- Ignore unavailable to you. Want to Upgrade?

To: Miljenko Zuanic who wrote (280)	6/16/2004 12:10:55 AM
From: biofreak	Read Replies (1) \| Respond to of 362

Dose escalation study of pivanex (a histone deacetylase inhibitor) in combination with docetaxel for advanced non-small cell lung cancer. Abstract No: 7279 Author(s): T. Reid, A. Weeks, M. Vakil, T. Cosgriff, T. Harper, F. Valone, D. Magnuson, A. Bhatnagar; VA Palo Alto Health Care, Palo Alto, CA; Family Care Center, Collierville, TN; Wilshire Oncology Group, LeVerne, CA; Hematology Oncology Specialists, Metairie, LA; New Jersey Cancer Associates, Hackensack, NJ; Titan Pharmaceuticals, Inc, South San Francisco, CA Abstract: Background: Pivanex is a histone deacetylase inhibitor that induces tumor cell differentiation and/or apoptosis. It has been well tolerated in clinical trials and has shown preliminary evidence of efficacy as a single agent in pts with advanced non-small cell lung cancer (NSCLC). In a Phase II trial of advanced NSCLC, partial responses were observed in 3 pts out of 29 (10 %) who had received < 3 prior chemotherapy regimens. Treatment with a combination of Pivanex and docetaxel has demonstrated synergy for growth inhibition of NSCLC cell lines in vitro and for improved survival in animal models. Because Pivanex has shown: (1) an excellent safety profile, (2) promising activity in pts with NSCLC, (3) no overlapping toxicities with docetaxel, and (4) synergy with docetaxel, we undertook a dose escalation study to assess the safety of this drug combined with docetaxel. Methods: Pivanex was given IV over 6 hours/day on Days 1-3. Docetaxel was given on Day 4. The regimen was repeated every 3 weeks. Twelve pts with NSCLC were enrolled in dosage cohorts of 1.5 to 2.5 g/m2 of Pivanex followed by 75 mg/m2 of docetaxel. Results: The median age was 69 yrs, 9 were male, 5 had squamous cell, and 6 were Stage IV. All pts had received at least one prior chemo regimen, 7 had received 2 prior chemo regimens and 6 pts had prior radiotherapy. A median of 4 cycles of the combination regimen were administered. No dose-limiting toxicity was observed and AEs were not related to Pivanex dose. Grade 3 or 4 neutropenia, typically associated with docetaxel treatment, occurred in 9 (75%) pts. Other AEs were fatigue and dyspnea in 4 pts each, and anemia in 3 pts. Three pts responded: 2 pts had decrease in tumor size such that it met PR criteria per RECIST; and one pt had complete resolution of baseline abnormalities on PET scan. Conclusions: The study demonstrated that Pivanex, at doses up to 2.5 g/m2 can be administered safely in combination with 75 mg/m2 of docetaxel in the regimen described above. This dose is being used in an ongoing Phase IIb trial in relapsed NSCLC that will randomize 225 pts to Pivanex + docetaxel versus docetaxel alone.