title: Phase I study of sunitinib in combination with gemcitabine and capecitabine for first-line treatment of metastatic or unresectable renal cell carcinoma.
abstract: BACKGROUND
  The combination of gemcitabine plus capecitabine and sunitinib (GCS) shows activity in metastatic renal cell carcinoma (mRCC). We tested the multitargeted "chemo-switch" regimen as first-line treatment in patients with mRCC.
  
  
  METHODS
  We assessed the maximum tolerated dose and antitumor activity of GCS in treatment-naïve, advanced mRCC patients. Treatment consisted of intravenous gemcitabine on days 1 and 8, oral capecitabine twice daily on days 1-14, and oral sunitinib daily for six 21-day cycles, followed by sunitinib monotherapy at the investigator's discretion. Dose level 0 (DL0) was gemcitabine 1,000 mg/m(2) per day plus capecitabine 650 mg/m(2) per 12 hours plus sunitinib 37.5 mg/day; DL1 was gemcitabine 1,000 mg/m(2) per day plus capecitabine 850 mg/m(2) per 12 hours plus sunitinib 37.5 mg/day.
  
  
  RESULTS
  Sixteen patients were enrolled. At DL1, two of four patients had dose-limiting toxicity (DLT; grade 3 diarrhea and grade 4 thrombocytopenia). The dose was reduced to DL0 when only 1 of 12 patients experienced DLT (grade 3 diarrhea, grade 3 mucositis, and grade 3 thrombocytopenia). Dose reductions were frequent (58% of patients), and only seven patients were able to receive the three drugs for more than three cycles. One patient achieved a complete response, three had partial responses, and the best response for four was stable disease.
  
  
  CONCLUSIONS
  The safety profile of the combination does not seem manageable in this patient population. No further development of the combination is recommended.
authors.affiliation: Hospital del Mar, Barcelona, Spain; Hospital del Mar Medical Research Institute and Pompeu Fabra University, Barcelona, Spain joaquim_bellmunt@dfci.harvard.edu.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.affiliation: Vall d'Hebron University Hospital, Universitat Autonoma of Barcelona, Barcelona, Spain;
authors.forename: Cristina
authors.initials: C
authors.lastname: Suarez
authors.affiliation: Parc Taulí Sabadell Hospital Universitari, Barcelona, Spain;
authors.forename: Enrique
authors.initials: E
authors.lastname: Gallardo
authors.affiliation: Vall d'Hebron University Hospital, Universitat Autonoma of Barcelona, Barcelona, Spain;
authors.forename: Jordi
authors.initials: J
authors.lastname: Rodon
authors.affiliation: Hospital del Mar Medical Research Institute and Pompeu Fabra University, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Pons
authors.affiliation: Parc Taulí Sabadell Hospital Universitari, Barcelona, Spain;
authors.forename: Teresa
authors.initials: T
authors.lastname: Bonfill
authors.affiliation: Vall d'Hebron University Hospital, Universitat Autonoma of Barcelona, Barcelona, Spain;
authors.forename: Marta
authors.initials: M
authors.lastname: Beltran
authors.affiliation: Parc Taulí Sabadell Hospital Universitari, Barcelona, Spain;
authors.forename: Irene
authors.initials: I
authors.lastname: Moya
authors.affiliation: Hospital del Mar Medical Research Institute and Pompeu Fabra University, Barcelona, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Galtes
authors.affiliation: Hospital del Mar Medical Research Institute and Pompeu Fabra University, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Albanell
authors.affiliation: Vall d'Hebron University Hospital, Universitat Autonoma of Barcelona, Barcelona, Spain;
authors.forename: Joan
authors.initials: J
authors.lastname: Carles
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D000069287:Capecitabine; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D000077210:Sunitinib; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D007211:Indoles; D011758:Pyrroles; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; D000077210:Sunitinib; D000093542:Gemcitabine