title: Treating refractory advanced or metastatic urothelial carcinoma with interleukin-2: a phase II study.
abstract: Patients with refractory advanced or metastatic urothelial carcinoma derive only minor benefit from chemotherapy. Based on evidence that urothelial carcinoma may be associated with impaired immunological reactivity, we conducted a phase II trial of interleukin-2 (IL-2), a biologic response modifier, to assess its efficacy and toxicity in treating refractory advanced or metastatic urothelial carcinoma. Seventeen patients with urothelial carcinoma who had undergone no more than 1 cisplatin-containing chemotherapy regimen were treated with IL-2 at a dose of 3 x 10(6) IU/m(2)/day by continuous intravenous infusion for 4 consecutive days each week for 4 weeks. Cycles were to be repeated every 6 weeks until disease progression. Toxic effects could be assessed in all 17 patients and response in 13. The most common grade III and IV toxic effects included hypotension (13/17); anemia (6/17); thrombocytopenia (4/17); granulocytopenia (3/17); and, in 1 patient each, cardiac ischemia, bowel perforation, and an increase in creatinine level. One sudden death was assumed to be treatment related. Although we found no objective antitumor activity for IL-2, median patient survival was 10.5 months (95% confidence interval, 5.8 to 17.1 months), with a 15.9-month median survival for 3 patients with poor performance status and visceral metastases. Further clinical investigation of the biological effect of IL-2 in urothelial carcinoma may be warranted.
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Box 427, 1515 Holcombe Boulevard, Houston, TX 77030, USA. jekim@mdanderson.org
authors.forename: Jeri
authors.initials: J
authors.lastname: Kim
authors.forename: Randall E
authors.initials: RE
authors.lastname: Millikan
authors.forename: Terry L
authors.initials: TL
authors.lastname: Smith
authors.forename: Shi Ming
authors.initials: SM
authors.lastname: Tu
authors.forename: Lance C
authors.initials: LC
authors.lastname: Pagliaro
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Logothetis
mesh_terms: D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016879:Salvage Therapy; D016019:Survival Analysis; D017211:Treatment Failure; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
chemical_list: D007155:Immunologic Factors; D007376:Interleukin-2; D002945:Cisplatin