BACKGROUND: Regional infusion therapy with melphalan (LPAM) is an accepted treatment for advanced extremity melanoma. However, much room exists for improving the therapeutic index of this type of therapy. METHODS: Isolated limb infusion (ILI) with temozolomide (TMZ), a novel methylating agent, was performed using a nude rat bearing human melanoma xenograft. Additional rats were treated systemically with TMZ, or regionally with LPAM or 10% dimethyl sulfoxide (DMSO; control) using ILI. RESULTS: Rats that received systemic TMZ showed a poor tumor response and no tumor regression. In contrast, intra-arterial TMZ demonstrated a prolongation of tumor growth delay in a dose-responsive manner. In comparison with LPAM of equitoxic dose, TMZ provided both longer tumor growth delay and a greater number of tumor regressions. CONCLUSIONS: These data suggest that ILI with TMZ is an effective treatment for advanced extremity melanoma and may be better than LPAM in this setting.
BACKGROUND: Regional infusion therapy with melphalan (LPAM) is an accepted treatment for advanced extremity melanoma. However, much room exists for improving the therapeutic index of this type of therapy. METHODS: Isolated limb infusion (ILI) with temozolomide (TMZ), a novel methylating agent, was performed using a nude rat bearing humanmelanoma xenograft. Additional rats were treated systemically with TMZ, or regionally with LPAM or 10% dimethyl sulfoxide (DMSO; control) using ILI. RESULTS:Rats that received systemic TMZ showed a poor tumor response and no tumor regression. In contrast, intra-arterial TMZ demonstrated a prolongation of tumor growth delay in a dose-responsive manner. In comparison with LPAM of equitoxic dose, TMZ provided both longer tumor growth delay and a greater number of tumor regressions. CONCLUSIONS: These data suggest that ILI with TMZ is an effective treatment for advanced extremity melanoma and may be better than LPAM in this setting.
Authors: Christy Y Chai; Jeremiah L Deneve; Georgia M Beasley; Suroosh S Marzban; Y Ann Chen; Bhupendra Rawal; Stephen R Grobmyer; Steven N Hochwald; Douglas S Tyler; Jonathan S Zager Journal: Ann Surg Oncol Date: 2011-12-06 Impact factor: 5.344
Authors: Betty S Jiang; Paul J Speicher; Samantha Thomas; Paul J Mosca; Amy P Abernethy; Douglas S Tyler Journal: Ann Surg Oncol Date: 2014-08-14 Impact factor: 5.344
Authors: Georgia M Beasley; Paul Speicher; Christina K Augustine; Paul C Dolber; Bercedis L Peterson; Ketan Sharma; Paul J Mosca; Richard Royal; Merrick Ross; Jonathan S Zager; Douglas S Tyler Journal: Ann Surg Oncol Date: 2014-08-22 Impact factor: 5.344
Authors: Yoshihiro Tokuhisa; Michael E Lidsky; Hiroaki Toshimitsu; Ryan S Turley; Georgia M Beasley; Tomio Ueno; Ketan Sharma; Christina K Augustine; Douglas S Tyler Journal: Ann Surg Oncol Date: 2013-11-27 Impact factor: 5.344