The pharmacologic basis of ifosfamide use in adult patients with advanced soft tissue sarcomas.
The treatment outcome of patients with locally advanced and metastatic soft tissue sarcomas is poor. Doxorubicin is regarded as standard treatment, but its use is featured by the occurrence of cardiotoxicity. This hinders the administration of this drug at high doses or in combination with, in theory, attractive newly developed targeted drugs, such as vascular endothelial growth factor (VEGF) pathway inhibitors. The combination of doxorubicin and VEGF pathway inhibitors has been shown to yield an unacceptable high rate of cardiomyopathy. Ifosfamide is the only drug that consistently shows response rates comparable to those of doxorubicin. The lack of cardiotoxicity renders this drug a much more attractive alternative than doxorubicin to be explored at high doses or as part of new drug combinations. This review addresses the clinical pharmacology, metabolism, and present role of ifosfamide in the treatment of locally advanced and/or metastatic soft tissue sarcomas, excluding gastrointestinal stromal tumors, the Ewing-like sarcomas, and other small blue round cell tumors. Furthermore, this review focuses on the anticipated growing role of ifosfamide in the development of new treatment strategies.
Tascilar
Metin
M
Department of Medical Oncology, Erasmus University Medical Center Rotterdam-Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075EA Rotterdam, The Netherlands.
Loos
Walter J
WJ
Seynaeve
Caroline
C
Verweij
Jaap
J
Sleijfer
Stefan
S
D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D018450:Disease Progression; D004317:Doxorubicin / Q000494:pharmacology; D004358:Drug Therapy / Q000379:methods; D006801:Humans; D007069:Ifosfamide / Q000494:pharmacology*; D008954:Models, Biological; D009362:Neoplasm Metastasis; D012509:Sarcoma / Q000188:drug therapy*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D004317:Doxorubicin; D007069:Ifosfamide