title: A phase I study of the safety and pharmacokinetics of the combination of pertuzumab (rhuMab 2C4) and capecitabine in patients with advanced solid tumors.
abstract: OBJECTIVE
  To study the safety, pharmacokinetics, and recommended dose of the combination of pertuzumab, a humanized monoclonal antibody HER2-dimerization inhibitor, and capecitabine in patients with advanced malignancies.
  
  
  METHODS
  Patients that had progressed to standard treatment were treated with pertuzumab at a fixed dose of 1,050 mg given i.v. on day 1 plus capecitabine at doses of 825-1,000-1,250 mg/m(2), twice daily orally on days 1 to 14 of each 21-day treatment cycle, in three sequential cohorts. The pharmacokinetics of capecitabine and pertuzumab were studied. Patients received a single dose of capecitabine in a pretreatment phase (day -7) followed by serum sampling for capecitabine and its metabolites.
  
  
  RESULTS
  Nineteen patients were accrued and 18 were assessable. The combination of capecitabine and pertuzumab was well tolerated at all dose levels and no dose-limiting toxicities were observed. The most frequent adverse event was asthenia, which was grade 3 in two patients. One asymptomatic pulmonary embolism occurred. No other grade 3 or 4 adverse events or cardiac or left ventricular ejection fraction events were reported. There was no apparent change in the pharmacokinetics of capecitabine and its metabolites when combined with pertuzumab. The pharmacokinetics of pertuzumab was apparently not modified when administered with capecitabine. Disease stabilization was observed in 11 patients.
  
  
  CONCLUSIONS
  Pertuzumab and capecitabine were well tolerated at all dose levels. Escalation beyond the highest dose level tested was not planned, as this included the recommended doses of monotherapy for both drugs. In conclusion, this combination is ready for phase II testing.
authors.affiliation: Medical Oncology Department, Hospital Clinic, Barcelona, Spain. jalbanell@imas.imim.es
authors.forename: Joan
authors.initials: J
authors.lastname: Albanell
authors.forename: Clara
authors.initials: C
authors.lastname: Montagut
authors.forename: Eileen T
authors.initials: ET
authors.lastname: Jones
authors.forename: Linda
authors.initials: L
authors.lastname: Pronk
authors.forename: Begoña
authors.initials: B
authors.lastname: Mellado
authors.forename: Janette
authors.initials: J
authors.lastname: Beech
authors.forename: Pere
authors.initials: P
authors.lastname: Gascon
authors.forename: Gerhard
authors.initials: G
authors.lastname: Zugmaier
authors.forename: Michael
authors.initials: M
authors.lastname: Brewster
authors.forename: Mark P
authors.initials: MP
authors.lastname: Saunders
authors.forename: Juan W
authors.initials: JW
authors.lastname: Valle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069287:Capecitabine; D002648:Child; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000069287:Capecitabine; C485206:pertuzumab; D005472:Fluorouracil