title: Phase I study of capecitabine combined with radioembolization using yttrium-90 resin microspheres (SIR-Spheres) in patients with advanced cancer.
abstract: BACKGROUND
  This was a prospective single-centre, phase I study to document the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended phase II dose for future study of capecitabine in combination with radioembolization.
  
  
  METHODS
  Patients with advanced unresectable liver-dominant cancer were enrolled in a 3+3 design with escalating doses of capecitabine (375-1000 mg/m(2) b.i.d.) for 14 days every 21 days. Radioembolization with (90)Y-resin microspheres was administered using a sequential lobar approach with two cycles of capecitabine.
  
  
  RESULTS
  Twenty-four patients (17 colorectal) were enrolled. The MTD was not reached. Haematologic events were generally mild. Common grade 1/2 non-haematologic toxicities included transient transaminitis/alkaline phosphatase elevation (9 (37.5%) patients), nausea (9 (37.5%)), abdominal pain (7 (29.0%)), fatigue (7 (29.0%)), and hand-foot syndrome or rash/desquamation (7 (29.0%)). One patient experienced a partial gastric antral perforation with a capecitabine dose of 750 mg/m(2). The best response was partial response in four (16.7%) patients, stable disease in 17 (70.8%) and progression in three (12.5%). Median time to progression and overall survival of the metastatic colorectal cancer cohort was 6.4 and 8.1 months, respectively.
  
  
  CONCLUSIONS
  This combined modality treatment was generally well tolerated with encouraging clinical activity. Capecitabine 1000 mg/m(2) b.i.d. is recommended for phase II study with sequential lobar radioembolization.
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Cohen
authors.affiliation: Department of Radiation Oncology, Karmanos Cancer Center, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Konski
authors.affiliation: Department of Radiology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
authors.forename: S
authors.initials: S
authors.lastname: Putnam
authors.affiliation: Department of Radiology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Ball
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Meyer
authors.affiliation: Department of Radiology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
authors.forename: J Q
authors.initials: JQ
authors.lastname: Yu
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
authors.forename: I
authors.initials: I
authors.lastname: Astsaturov
authors.affiliation: Clinical Trials Office, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
authors.forename: C
authors.initials: C
authors.lastname: Marlow
authors.affiliation: Clinical Trials Office, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
authors.forename: A
authors.initials: A
authors.lastname: Dickens
authors.affiliation: Sirtex Medical Ltd, Sydney, New South Wales, Australia.
authors.forename: D N
authors.initials: DN
authors.lastname: Cade
authors.affiliation: Division of Hematology and Oncology, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Meropol
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000069287:Capecitabine; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004621:Embolization, Therapeutic / Q000379:methods*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008863:Microspheres; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D011446:Prospective Studies; D015021:Yttrium Radioisotopes / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D000964:Antimetabolites, Antineoplastic; D015021:Yttrium Radioisotopes; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil