title: A phase II trial of 17-(Allylamino)-17-demethoxygeldanamycin in patients with papillary and clear cell renal cell carcinoma.
abstract: The aim of this study was to determine the antitumor activity of 17-(Allylamino)-17-demethoxyge-ldanamycin (17-AAG), a heat shock protein 90(hsp90) inhibitor in patients with metastatic papillary renal cell carcinoma (RCC) or metastatic clear cell RCC. Eligible patients were divided into 2 cohorts based on histological subtype: papillary or clear cell RCC. All patients had advanced RCC with measurable disease, a Karnofsky performance status of at least 70, and no evidence of brain metastases. Twelve patients with clear cell RCC and 8 patients with papillary RCC were treated with 17-AAG on this phase II trial. 17-AAG was given intravenously at 220 mg/m(2) twice weekly for 2 weeks followed by a week of rest. Cycle length was 21 days. No patient in either cohort achieved a complete or partial response. Toxicities included elevated liver function tests, optic neuritis, dyspnea, fatigue, and gastrointestinal side effects. Six of the 20 patients required dose reduction. At the dose and schedule used in this trial, 17-AAG did not achieve objective response in the treatment of clear cell or papillary renal cell carcinoma patients.
authors.affiliation: From the Genitourinary Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Ronnen
authors.forename: G Varuni
authors.initials: GV
authors.lastname: Kondagunta
authors.forename: Nicole
authors.initials: N
authors.lastname: Ishill
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Sweeney
authors.forename: John K
authors.initials: JK
authors.lastname: Deluca
authors.forename: Lawrence
authors.initials: L
authors.lastname: Schwartz
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bacik
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016227:Benzoquinones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002291:Carcinoma, Papillary / Q000188:drug therapy* / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D047029:Lactams, Macrocyclic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D047029:Lactams, Macrocyclic; C112765:tanespimycin