Temozolomide is a novel regional infusion agent for the treatment of advanced extremity melanoma

Am J Surg. 2004 Nov;188(5):532-7. doi: 10.1016/j.amjsurg.2004.07.014.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Antineoplastic Agents, Alkylating / pharmacology*
  • Chemotherapy, Cancer, Regional Perfusion
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / pharmacology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Extremities
  • Female
  • Infusions, Parenteral
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Melphalan / pharmacology*
  • Probability
  • Random Allocation
  • Rats
  • Rats, Nude
  • Reference Values
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Survival Rate
  • Temozolomide
  • Transplantation, Heterologous
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • Melphalan
  • Temozolomide