Temozolomide is a novel regional infusion agent for the treatment of advanced extremity melanoma.
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.
Ueno
Tomio
T
Department of Surgery, Box 3118 Medical Center, Duke University Medical Center, Durham, NC 27710, USA.
Ko
Sae Hee
SH
Grubbs
Elizabeth
E
Pruitt
Scott K
SK
Friedman
Henry S
HS
Tyler
Douglas S
DS
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
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D008558:Melphalan; D000077204:Temozolomide