title: Phase II study of sorafenib in patients with sunitinib-refractory metastatic renal cell cancer.
abstract: OBJECTIVE
  No previous prospective trials have been reported with sorafenib in patients with sunitinib-refractory metastatic renal cell cancer (MRCC). We conducted a multicenter study to determine the activity and tolerability of sorafenib as second-line therapy after sunitinib progression in MRCC.
  
  
  METHODS
  Between January 2006 and September 2008, 52 patients were enrolled onto this single-arm phase II study. All patients received sorafenib 400 mg orally twice a day until disease progression or intolerable toxicity. The primary end point was objective response rate (complete or partial response) evaluated every 8 weeks by use of the Response Evaluation Criteria in Solid Tumors; secondary end points were toxicity, time to progression (TTP), and overall survival (OS).
  
  
  RESULTS
  All patients were included in response and safety analyses. Partial responses were observed in 9.6% of patients (five of 52 patients; 95% CI, 5% to 17%) after two cycles. Grade 1 to 2 fatigue, diarrhea, nausea/vomiting, rash, and neutropenia were the most common side effects, noted in 16 (30.8%), 19 (36.5%), 20 (38.5%), 19 (36.5%), and 20 patients (38.5%), respectively. The most common grade 3 toxicity was diarrhea, noted in six patients (11.5%). Median TTP was 16 weeks (range, 8 to 40 weeks), and median OS was 32 weeks (range, 16 to 64 weeks).
  
  
  CONCLUSIONS
  Although well tolerated, sorafenib shows limited efficacy in sunitinib-refractory MRCC. Further randomized trials comparing sorafenib with other drugs that target different biologic pathways are needed to define the best second-line treatment option in these patients.
authors: Dipartimento di Endocrinologia ed Oncologia Clinica e Molecolare, Università Federico II, Napoli, Italy. giuseppedilorenzoncol@hotmail.com
authors: Giuseppe
authors: G
authors: Di Lorenzo
authors: Giacomo
authors: G
authors: Cartenì
authors: Riccardo
authors: R
authors: Autorino
authors: Gianni
authors: G
authors: Bruni
authors: Marianna
authors: M
authors: Tudini
authors: Mimma
authors: M
authors: Rizzo
authors: Michele
authors: M
authors: Aieta
authors: Antonio
authors: A
authors: Gonnella
authors: Pasquale
authors: P
authors: Rescigno
authors: Sisto
authors: S
authors: Perdonà
authors: Gianluca
authors: G
authors: Giannarini
authors: Sandro
authors: S
authors: Pignata
authors: Nicola
authors: N
authors: Longo
authors: Giovannella
authors: G
authors: Palmieri
authors: Ciro
authors: C
authors: Imbimbo
authors: Michele
authors: M
authors: De Laurentiis
authors: Vincenzo
authors: V
authors: Mirone
authors: Corrado
authors: C
authors: Ficorella
authors: Sabino
authors: S
authors: De Placido
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use; D000077157:Sorafenib; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D000077210:Sunitinib