Irofulven, a novel inhibitor of DNA synthesis, in metastatic renal cell cancer.
Irofulven (6-Hydroxymethylacylfulvene, MGI-114) is the first of a new class of anticancer compounds the acylfulvenes which are derived from the natural product, illudin S. Irofulven is a potent anticancer agent with activity against a broad range of human tumors in vitro and in vivo. Irofulven covalently binds to DNA, inhibits DNA synthesis and induces apoptosis. Clinical activity has been observed in phase I studies. Because disease stabilizations were observed in kidney cancer patients in the phase I trials, we performed a phase II trial of irofulven in this patient population. Twenty patients were accrued. Irofulven (11 milligrams per meter squared per day) was administered as a 5 minute intravenous infusion for 5 consecutive days, and response was evaluated every 8 weeks. There were no objective responses. The most common toxicities were nausea, emesis, and thrombocytopenia. Irofulven, at the dose and schedule administered in this trial, showed no effect in metastatic renal cell cancer.
Amato
Robert J
RJ
Scott Department of Urology, Baylor College of Medicine, Houston, TX 77030, USA. ramato@www.urol.bcm.tmc.edu
Perez
Cherie
C
Pagliaro
Lance
L
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D019384:Nucleic Acid Synthesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012717:Sesquiterpenes / Q000009:adverse effects / Q000627:therapeutic use*
D019384:Nucleic Acid Synthesis Inhibitors; D012717:Sesquiterpenes; C102714:irofulven