title: Results from a Phase I Study of Lapatinib with Gemcitabine and Cisplatin in Advanced or Metastatic Bladder Cancer: EORTC Trial 30061.
abstract: OBJECTIVE
  Lapatinib is a potent HER1 and HER2 inhibitor. Gemcitabine-cisplatin (GC) is a standard chemotherapy regimen for advanced/metastatic bladder cancer. This phase I study examined the safety of lapatinib in combination with GC in patients with bladder cancer. The primary aim was to determine the maximum tolerated dose (MTD) of lapatinib in combination with GC.
  
  
  METHODS
  A 3 + 3 dose escalation protocol was used with lapatinib at 750, 1,000 and then 1,250 mg. It was dosed daily with gemcitabine (1,000 mg/m2 on days 1, 8 and 15) and cisplatin (70 mg/m2 on day 2) every 28 days. In all, 18 patients with a median age of 63 years (range 50-77) were included; 3/6, 3/5 and 6/7 patients received lapatinib at 750, 1,000 and 1,250 mg, combined with GC, in cohorts 1, 2 and 3, respectively.
  
  
  RESULTS
  No dose-limiting toxicities (DLTs) were observed in cohort 1 or 2 (3 patients each); in cohort 3 (2 × 3 patients), 1 of the 6 patients presented DLTs (grade 4, treatment-related febrile neutropenia and renal failure). Twelve patients received 6 cycles.
  
  
  CONCLUSIONS
  Lapatinib at 750-1,250 mg combined with GC appears safe and tolerable. The MTD of lapatinib combined with GC in bladder cancer was 1,250 mg.
authors.affiliation: Department of Medical Oncology, San Camillo and Forlanini Hospital, Rome, Italy.
authors.forename: Linda
authors.initials: L
authors.lastname: Cerbone
authors.forename: Cora N
authors.initials: CN
authors.lastname: Sternberg
authors.forename: Lisa
authors.initials: L
authors.lastname: Sengeløv
authors.forename: Mads
authors.initials: M
authors.lastname: Agerbaek
authors.forename: Carla
authors.initials: C
authors.lastname: Van Herpen
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marreaud
authors.forename: Sandra
authors.initials: S
authors.lastname: Collette
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
authors.forename: Gedske
authors.initials: G
authors.lastname: Daugaard
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D014408:Biomarkers, Tumor / Q000032:analysis; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000032:analysis; D064147:Febrile Neutropenia / Q000139:chemically induced; D005260:Female; D006801:Humans; D007391:International Cooperation; D000077341:Lapatinib; 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; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D051437:Renal Insufficiency / Q000139:chemically induced; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D002945:Cisplatin; D003841:Deoxycytidine; D066246:ErbB Receptors; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000093542:Gemcitabine; C512478:EGFR protein, human; C508053:ERBB2 protein, human