title: Phase I trial of sunitinib and temsirolimus in metastatic renal cell carcinoma.
abstract: BACKGROUND
  Preclinical data suggest that anti-vascular endothelial growth factor agents combined with mammalian target of rapamycin inhibitors yield synergistic antitumor effects. A phase I trial with a 3+3 dose escalation design of S with T was stopped after the first dose pair led to 2 of 3 patients experiencing dose-limiting toxicity (DLT).
  
  
  METHODS
  To explore multiple potential dosing pairs of S and T, a 2-stage outcome-adaptive Bayesian dose-finding method was designed. The primary objective was to find the MTD of S and T in patients with advanced renal cell carcinoma. A 3-week treatment cycle consisted of daily S, 2 weeks of treatment, 1 week without treatment, and weekly T.
  
  
  RESULTS
  Twenty patients received study drugs; the median number of previous therapies was 1. The number of patients (S and T doses in mg) was: 2 (S, 12.5; T, 6), 1 (S, 25; T, 12.5), 1 (S, 12.5; T, 8), 8 (S, 12.5 alternate 25; T, 9), 2 (S, 25; T, 6), 2 (S, 25 alternate 37.5; T, 6), 2 (S, 37.5; T, 6), and 2 (S, 37.5; T, 8). Six patients required dose reduction, 3 because of Grade 3 stomatitis, 2 because of Grade 3 thrombocytopenia; the mean number of cycles was 6.6 ± 5.3, the mean time during study was 159 ± 120 days. One patient experienced a DLT in cycle 1 and was nonevaluable, 1 had a partial response, 16 had stable disease, and 2 had progressive disease as best response. There were 21 Grade 3/4 adverse events but no treatment-related deaths.
  
  
  CONCLUSIONS
  The MTD of S and T were not determined because of premature trial closure. S 37.5 mg/d, 2 weeks of treatment, 1 week with no treatment, and T 8 mg to 10 mg weekly are close to the MTD.
authors.affiliation: Division of Cancer Medicine Fellowship Program, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Campbell
authors.affiliation: Essential Health, Essentia Health Duluth Cancer Center, Duluth, MN.
authors.forename: Randall E
authors.initials: RE
authors.lastname: Millikan
authors.affiliation: Diagnostic Radiology Department, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Emre
authors.initials: E
authors.lastname: Altinmakas
authors.affiliation: Biostatistics Department, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Lianchun
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Biostatistics, West Virginia University, Robert C. Byrd Health Sciences Center, Morgantown, WV.
authors.forename: Sin Jen
authors.initials: SJ
authors.lastname: Wen
authors.affiliation: Genitourinary Medical Oncology Department, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Arlene O
authors.initials: AO
authors.lastname: Siefker-Radtke
authors.affiliation: Genitourinary Medical Oncology Department, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Ana
authors.initials: A
authors.lastname: Aparicio
authors.affiliation: Genitourinary Medical Oncology Department, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Corn
authors.affiliation: Genitourinary Medical Oncology Department, University of Texas M.D. Anderson Cancer Center, Houston, TX. Electronic address: ntannir@mdanderson.org.
authors.forename: Nizar M
authors.initials: NM
authors.lastname: Tannir
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D001499:Bayes Theorem; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077210:Sunitinib; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; C401859:temsirolimus; D000077210:Sunitinib; D020123:Sirolimus
keywords: Combination; Kidney; Neoplasm; Study; Therapeutics