title: Phase II trial of weekly alternating sequential BIBF 1120 and afatinib for advanced colorectal cancer.
abstract: OBJECTIVE
  The feasibility of an alternating regimen of BIBF 1120, a potent, oral, triple angiokinase inhibitor, and afatinib (BIBW 2992), a potent ErbB family blocker, was explored in patients with advanced pretreated colorectal cancer (CRC).
  
  
  METHODS
  Patients received repeated courses of alternating 7-day treatment periods, first with BIBF 1120 250 mg twice daily and then afatinib 50 mg once daily. The primary endpoint was the objective response rate; the incidence/severity of adverse events (AEs) and pharmacokinetics (PK) were determined.
  
  
  RESULTS
  Forty-six patients (≥4 prior lines, most anti-VEGF and/or -EGFR pretreated) received BIBF 1120 and afatinib. No objective responses were observed; the best response was stable disease in 20 patients (43.5%). Seven patients (15.2%) remained progression-free for ≥16 weeks. Median progression-free survival was 1.9 months; median overall survival was 5.5 months. The most frequent drug-related AEs were diarrhoea (80.4%), asthenia (47.8%), nausea (43.5%) and rash (41.3%). PK assessments did not show obvious alterations for either drug.
  
  
  CONCLUSIONS
  Weekly alternating administration of BIBF 1120 and afatinib is feasible; however, its efficacy was limited in this highly palliative patient population.
authors: CHU Reims, Reims, France. obouche@chu-reims.fr
authors: Olivier
authors: O
authors: Bouche
authors: Frederique
authors: F
authors: Maindrault-Goebel
authors: Michel
authors: M
authors: Ducreux
authors: Gerard
authors: G
authors: Lledo
authors: Thierry
authors: T
authors: Andre
authors: Peter
authors: P
authors: Stopfer
authors: Nadia
authors: N
authors: Amellal
authors: Michael
authors: M
authors: Merger
authors: Aimery
authors: A
authors: De Gramont
mesh_terms: D000077716:Afatinib; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D015996:Survival Rate
chemical_list: D007211:Indoles; D011799:Quinazolines; D000077716:Afatinib; C530716:nintedanib