Phase 2 trial of talabostat and cisplatin in patients with stage IV melanoma
| Autor: | J. Stephenson, Steven J. O'Day, G. Frenette, Anna C. Pavlick, Z. Yang, C. Cunningham, K. Khan, M. J. Uprichard, Ricardo J. Gonzalez, V. Vrhovac |
|---|---|
| Rok vydání: | 2006 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 24:8040-8040 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2006.24.18_suppl.8040 |
| Popis: | 8040 Background: Talabostat (TAL) is an oral inhibitor of dipeptidyl peptidases such as fibroblast activation protein found on the stroma of tumors, draining lymph nodes, and in melanomas. TAL up-regulates cytokines and chemokines, leading to specific T-cell immunity and T-cell independent activity. TAL significantly enhances the activity of cisplatin (C) in mice, and reduces tumor size >60% in melanoma xenografts (A375, A2058). This trial evaluated the activity of TAL and C in patients with Stage IV melanoma. Methods: Open-label, single-arm, Phase 2 study of 4 x 3-week cycles of C-75mg/m2 (Day 1) and TAL-300mcg BID orally on Days 2–15 with dose-escalation to TAL-400mcg BID depending on tolerability. Single-agent TAL could be continued beyond 4 cycles until disease progression or unacceptable toxicity. Eligibility criteria included: ≤1 prior bio- or chemotherapy regimen, ECOG 0–2, measureable disease per RECIST, no symptomatic CNS metastases, LDH, ALT, and AST 2). Grade 3 toxicities were neutropenia, fatigue, and dehydration, all at 3.4%. Grade 4 toxicities were organ failure, renal failure, and PD (1 patient each). 4 patients died due to PD, and 1 each due to renal and organ failure. Conclusions: The combination of TAL and C is active in patients with Stage IV melanoma. Most AEs were related to C-associated nausea and vomiting, limiting the oral delivery of TAL. Additional studies of TAL in melanoma with other drug combinations are warranted. [Table: see text] |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|