title: A phase I/II study of lenalidomide in combination with sunitinib in patients with advanced or metastatic renal cell carcinoma.
abstract: BACKGROUND
  This phase I/II study was conducted to determine the maximum tolerated dose (MTD), safety, and efficacy of lenalidomide plus sunitinib in metastatic renal cell carcinoma (RCC) patients.
  
  
  METHODS
  Patients with histologically confirmed, metastatic RCC were treated with 10 mg/day lenalidomide plus 37.5 mg/day sunitinib, orally in 21-day cycles. Doses were escalated to determine the MTD in phase I, with additional patients planned at this dose in phase II. Primary end points were MTD and response rate.
  
  
  RESULTS
  Sixteen patients received a median of 2, 3, and 5 cycles in cohort 1 [lenalidomide 10 mg (days 1-21) and sunitinib 37.5 mg (days 1-21)], cohort 2 [lenalidomide 10 mg (days 1-21) and sunitinib 37.5 mg (days 1-14)], and cohort 3 [lenalidomide 15 mg (days 1-21) and sunitinib 37.5 mg (days 1-14)], respectively. Median treatment durations were 41, 63, and 97 days for lenalidomide; and 41, 57, and 97.5 days for sunitinib. The MTD was found to be continuous dosing of lenalidomide 10 mg/day plus sunitinib 37.5 mg/day for 14 of 21 days. Dose-limiting toxicities included neutropenia, leukopenia, thrombocytopenia, asthenia, atrial fibrillation, and increased transaminases. The most frequent grade 3-4 treatment-emergent adverse events were hematologic, including neutropenia and leukopenia. One patient achieved partial response, and seven had stable disease of which three were confirmed at subsequent tumor assessments. B cells and several T-cell subsets were modulated versus baseline.
  
  
  CONCLUSIONS
  The dose schedules of lenalidomide and sunitinib evaluated in this study were not well tolerated; cumulative toxicity precluded enrollment at the MTD.
authors.affiliation: Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Glickman Urological Institute, Cleveland. Electronic address: rinib2@ccf.org.
authors.forename: B
authors.initials: B
authors.lastname: Rini
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor.
authors.forename: B
authors.initials: B
authors.lastname: Redman
authors.affiliation: Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Glickman Urological Institute, Cleveland.
authors.forename: J A
authors.initials: JA
authors.lastname: Garcia
authors.affiliation: Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville.
authors.forename: H A
authors.initials: HA
authors.lastname: Burris
authors.affiliation: Celgene Corporation.
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.affiliation: Celgene Corporation.
authors.forename: A
authors.initials: A
authors.lastname: Fandi
authors.affiliation: Celgene Corporation.
authors.forename: R
authors.initials: R
authors.lastname: Beck
authors.affiliation: Celgene Corporation.
authors.forename: U
authors.initials: U
authors.lastname: Jungnelius
authors.affiliation: Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville.
authors.forename: J R
authors.initials: JR
authors.lastname: Infante
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D000077269:Lenalidomide; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D000077210:Sunitinib; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D013792:Thalidomide; D000077269:Lenalidomide; D000077210:Sunitinib
keywords: lenalidomide; maximum tolerated dose; metastatic renal cell carcinoma; phase I/II; sunitinib