title: A phase I trial of sorafenib plus gemcitabine and capecitabine for patients with advanced renal cell carcinoma: New York Cancer Consortium Trial NCI 6981.
abstract: OBJECTIVE
  To define the safety [dose limiting toxicity (DLT)] and recommended phase II dose of the combination of sorafenib plus gemcitabine and capecitabine for advanced renal cell carcinoma (RCC).
  
  
  METHODS
  In this phase I dose-escalation study, cohorts of 3 to 6 patients with metastatic RCC received sorafenib (200 or 400 mg po BID), gemcitabine (750 or 1000 mg/m(2) intravenous on days 1 and 8), and capecitabine (415 or 622 mg/m(2) po BID days 1-14) every 21 days using a standard 3+3 design.
  
  
  RESULTS
  Fifteen patients with advanced RCC (93% with clear cell histology and 87% treatment naive) received treatment. The recommended phase II doses for the combination were sorafenib 200 mg/m(2) BID continuously plus gemcitabine 750 mg/m(2) intravenous days 1 and 8 and capecitabine 415 mg/m(2) BID days 1 to 14, every 21 days. Of the 15 patients, 3 developed dose-limiting hand-foot syndrome during the first 2 cycles; 2 additional DLT's were grade 3 mucositis and transaminase elevation. Four of 14 evaluable patients had a partial response by response evaluation criteria in solid tumors (29%; 95% confidence interval (CI): 8, 58%). Median progression-free survival was 7.5 months (95% CI-0, 18.7), and median overall survival has not been reached at a median follow-up of 28.8 months. The median number of treatment cycles given was 7 (range, 2-38+).
  
  
  CONCLUSIONS
  The combination of sorafenib plus gemcitabine and capecitabine is tolerable, but requires attenuation of sorafenib and capecitabine dosing because of the overlapping toxicity of hand-foot syndrome. Antitumor activity was observed leading to an ongoing phase II trial.
authors.affiliation: Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York, NY 10065, USA. stt2007@med.cornell.edu
authors.forename: Scott T
authors.initials: ST
authors.lastname: Tagawa
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Milowsky
authors.forename: Stephanie
authors.initials: S
authors.lastname: Jeske
authors.forename: Madhu
authors.initials: M
authors.lastname: Mazumdar
authors.forename: Sophia
authors.initials: S
authors.lastname: Kung
authors.forename: Max
authors.initials: M
authors.lastname: Sung
authors.forename: Deborah
authors.initials: D
authors.lastname: Lehrer
authors.forename: Daniel
authors.initials: D
authors.lastname: Matulich
authors.forename: Jodi
authors.initials: J
authors.lastname: Selzer
authors.forename: John J
authors.initials: JJ
authors.lastname: Wright
authors.forename: David M
authors.initials: DM
authors.lastname: Nanus
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D000069287:Capecitabine; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage; D000077157:Sorafenib; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D003841:Deoxycytidine; D009536:Niacinamide; D000069287:Capecitabine; D000077157:Sorafenib; D005472:Fluorouracil; D000093542:Gemcitabine