title: Phase I study combining treatment with temsirolimus and sunitinib malate in patients with advanced renal cell carcinoma.
abstract: OBJECTIVE
  Concurrent inhibition of multiple oncogenic signaling pathways might improve the efficacy of anticancer agents and abrogate resistance mechanisms. This phase I study evaluated temsirolimus in combination with sunitinib in patients with advanced RCC.
  
  
  METHODS
  Eligibility included advanced RCC and <or= 2 previous systemic regimens. At the starting dose, temsirolimus 15 mg was administered by intravenous (I.V.) infusion once weekly, and sunitinib 25 mg was administered orally once daily for 4 weeks, followed by a 2-week rest period.
  
  
  RESULTS
  In the first cohort, dose-limiting toxicities (grade 3 treatment-related toxicities that lasted >or= 7 days) were observed in 2 of 3 patients. One patient experienced grade 3 rash during week 3, which led to treatment discontinuation. A second patient had grade 3 thrombocytopenia (platelet count, 48,000/microL), cellulitis, and gout during week 3 and was hospitalized; platelets recovered to 109,000/microL 4 days after discontinuation of protocol therapy. A third patient experienced rash, asthenia, diarrhea, stomatitis, constipation, fever, and rectal hemorrhage, all of which were mild in severity. The study was terminated because of dose-limiting toxicity observed at low starting doses of both agents.
  
  
  CONCLUSIONS
  Concomitant use of I.V. temsirolimus 15 mg weekly and oral sunitinib 25 mg daily (4 weeks on, 2 weeks off) is not recommended.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA.
authors.forename: Premal H
authors.initials: PH
authors.lastname: Patel
authors.forename: Peggy L
authors.initials: PL
authors.lastname: Senico
authors.forename: Rafael E
authors.initials: RE
authors.lastname: Curiel
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D002481:Cellulitis / Q000139:chemically induced*; D003967:Diarrhea / Q000139:chemically induced; D003875:Drug Eruptions / Q000209:etiology*; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; D007262:Infusions, Intravenous; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D013280:Stomatitis / Q000139:chemically induced*; D000077210:Sunitinib; D013921:Thrombocytopenia / Q000139:chemically induced*; D016896:Treatment Outcome
chemical_list: D007211:Indoles; D011758:Pyrroles; C401859:temsirolimus; D000077210:Sunitinib; D020123:Sirolimus