title: Phase I trial of sunitinib malate plus interferon-alpha for patients with metastatic renal cell carcinoma.
abstract: BACKGROUND
  Sunitinib malate is an oral, multitargeted tyrosine kinase inhibitor that has demonstrated superior efficacy over interferon (IFN)-alpha in a phase III trial in first-line, metastatic renal cell carcinoma (RCC). Herein, we report the results of a phase I dose-finding study of sunitinib in combination with IFN-alpha as first-line treatment in patients with metastatic RCC.
  
  
  METHODS
  Treatment-naive patients with clear-cell metastatic RCC received sunitinib at a starting dose of 50 mg or 37.5 mg orally once daily in 6-week cycles (schedule 4/2) plus IFN-alpha at a starting dose of 3 MU subcutaneously 3 times a week, with weekly intrapatient dose escalation to a maximum of 9 MU as tolerated. Patients who did not tolerate either drug received lower doses of either or had dose interruptions.
  
  
  RESULTS
  Twenty-five patients were enrolled; their median age was 64 years (range, 45-77 years). All patients experienced grade 3/4 treatment-emergent adverse events; the most common were neutropenia, fatigue, and thrombocytopenia. After a median of 4 cycles (range, 1-9 cycles), 3 patients (12%) had a partial response, and 20 (80%) had stable disease.
  
  
  CONCLUSIONS
  Although reduced starting doses were tolerated (37.5 mg for sunitinib and 3 MU for IFN-alpha), even these lower doses might not be well tolerated for long-term treatment of patients with metastatic RCC. Based on historical data, sunitinib on schedule 4/2 appears to be more effective as single-agent therapy. Further study of sunitinib plus IFN-alpha on this schedule is not being pursued in RCC.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. motzerr@mskcc.org
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
authors.forename: Gary
authors.initials: G
authors.lastname: Hudes
authors.forename: George
authors.initials: G
authors.lastname: Wilding
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Schwartz
authors.forename: Subramanian
authors.initials: S
authors.lastname: Hariharan
authors.forename: Susan
authors.initials: S
authors.lastname: Kempin
authors.forename: Rana
authors.initials: R
authors.lastname: Fayyad
authors.forename: Robert A
authors.initials: RA
authors.lastname: Figlin
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D005221:Fatigue / Q000139:chemically induced*; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D016898:Interferon-alpha / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced*; D011758:Pyrroles / Q000008:administration & dosage; D000077210:Sunitinib; D013921:Thrombocytopenia / Q000139:chemically induced*; D016896:Treatment Outcome
chemical_list: D007211:Indoles; D016898:Interferon-alpha; D011758:Pyrroles; D000077210:Sunitinib