title: Temozolomide is a novel regional infusion agent for the treatment of advanced extremity melanoma.
abstract: 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.
authors.affiliation: Department of Surgery, Box 3118 Medical Center, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Tomio
authors.initials: T
authors.lastname: Ueno
authors.forename: Sae Hee
authors.initials: SH
authors.lastname: Ko
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Grubbs
authors.forename: Scott K
authors.initials: SK
authors.lastname: Pruitt
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Tyler
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D010478:Chemotherapy, Cancer, Regional Perfusion; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005121:Extremities; D005260:Female; D007263:Infusions, Parenteral; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008558:Melphalan / Q000494:pharmacology*; D011336:Probability; D011897:Random Allocation; D051381:Rats; D011923:Rats, Nude; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D000077204:Temozolomide; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D008558:Melphalan; D000077204:Temozolomide