title: Bosutinib plus capecitabine for selected advanced solid tumours: results of a phase 1 dose-escalation study.
abstract: This phase 1 study evaluated the maximum tolerated dose (MTD), safety, and efficacy of bosutinib (competitive Src/Abl tyrosine kinase inhibitor) plus capecitabine.
  
  
  
  Patients with locally advanced/metastatic breast, pancreatic, or colorectal cancers; cholangiocarcinoma; or glioblastoma received bosutinib plus capecitabine at eight of nine possible dose combinations using an 'up-down' design to determine the toxicity contour of the combination.
  
  
  
  Among 32 enrolled patients, none of the 9 patients receiving MTD (bosutinib 300 mg once daily plus capecitabine 1000 mg m(-2) twice daily) experienced dose-limiting toxicities (DLTs). Overall, 2 out of 31 (6%) evaluable patients experienced DLTs (grade 3 neurologic pain (n=1); grade 3 pruritus/rash and increased alanine aminotransferase (n=1)). Most common treatment-related adverse events (AEs) were diarrhoea, nausea, vomiting, palmar-plantar erythrodysesthesia (PPE), fatigue; most frequent grade 3/4 AEs: PPE, fatigue, and increased alanine/aspartate aminotransferase. Although diarrhoea was common, 91% of affected patients experienced maximum grade 1/2 events that resolved. Best overall confirmed partial response or stable disease >24 weeks (all tumour types) was observed in 6 and 13% of patients.
  
  
  
  In this population of patients with advanced solid tumours, bosutinib plus capecitabine demonstrated a safety profile similar to that previously reported for bosutinib or capecitabine monotherapy; limited efficacy was observed.
authors.affiliation: Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center, and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Isakoff
authors.affiliation: Phase I Clinical Trials Program, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA.
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.affiliation: Institut de Cancerologie de l'Quest-Rene Gauducheau, Saint Herblain, Nantes Cedex 44805, France.
authors.forename: M
authors.initials: M
authors.lastname: Campone
authors.affiliation: START Madrid, Centro Integral Oncológico Clara Campal, Hospital Madrid Norte-Sanchinarro, C/Oña n°10, 28050 Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Calles
authors.affiliation: Oncology Clinical Statistics, Pfizer Inc, 10 Fawcett Street, Suite 2013, Cambridge, MA 02138, USA.
authors.forename: E
authors.initials: E
authors.lastname: Leip
authors.affiliation: Oncology Clinical Development, Pfizer Inc, 10 Fawcett Street, Suite 2013, Cambridge, MA 02138, USA.
authors.forename: K
authors.initials: K
authors.lastname: Turnbull
authors.affiliation: Oncology Late Phase Strategy Development, Pfizer Global Research and Development, 23-25 av du Dr Lannelongue, Paris 75668, France.
authors.forename: N
authors.initials: N
authors.lastname: Bardy-Bouxin
authors.affiliation: Oncology Clinical Development, Pfizer Global Research and Development, 23-25 av du Dr Lannelongue, Paris 75668, France.
authors.forename: L
authors.initials: L
authors.lastname: Duvillié
authors.affiliation: START Madrid, Centro Integral Oncológico Clara Campal, Hospital Madrid Norte-Sanchinarro, C/Oña n°10, 28050 Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Calvo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000814:Aniline Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects; D011804:Quinolines / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000814:Aniline Compounds; D009570:Nitriles; D011804:Quinolines; D003841:Deoxycytidine; C471992:bosutinib; D000069287:Capecitabine; D005472:Fluorouracil