Phase I dose-escalation study of aflibercept in combination with docetaxel and cisplatin in patients with advanced solid tumours

Br J Cancer. 2012 Aug 7;107(4):598-603. doi: 10.1038/bjc.2012.304. Epub 2012 Jul 12.


Background: This phase I cohort study investigated aflibercept (vascular endothelial growth factor (VEGF) trap) plus docetaxel and cisplatin in patients with advanced solid tumours.

Methods: Patients received intravenous aflibercept 4, 5, or 6 mg kg(-1) with docetaxel and cisplatin (75 mg m(-2) each) on day 1 of a 3-week cycle until progressive disease or unacceptable toxicity. Primary objectives were determining cycle 1 dose-limiting toxicities (DLTs) and the aflibercept recommended phase II trial dose (RP2D) for this combination.

Results: During the dose-escalation phase (n=16), there were two DLTs of febrile neutropenia (at 4 and 5 mg kg(-1)). Granulocyte colony-stimulating factor prophylaxis was subsequently recommended. The RP2D of aflibercept was established at 6 mg kg(-1) and administered to 14 additional patients. The most frequent grade 3/4 adverse events (AEs) were neutropenia (43.3%), stomatitis (20.0%), asthenia/fatigue (20.0%), and hypertension (16.7%). All-grade AEs associated with VEGF blockade included epistaxis (83.3%), dysphonia (70.0%), proteinuria (53.3%), and hypertension (50.0%). There were five partial responses (16.7%) and 18 cases of stable disease (60.0%) (lasting >3 months in 10 patients). There were no pharmacokinetic (PK) interactions between the three drugs.

Conclusion: Aflibercept 6 mg kg(-1) with docetaxel and cisplatin 75 mg m(-2) every 3 weeks is the RP2D based on tolerability, antitumour activity, and PKs.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cisplatin / administration & dosage*
  • Docetaxel
  • Drug Administration Schedule
  • Fatigue / chemically induced
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neutropenia / chemically induced
  • Receptors, Vascular Endothelial Growth Factor
  • Recombinant Fusion Proteins / administration & dosage*
  • Taxoids / administration & dosage*


  • Recombinant Fusion Proteins
  • Taxoids
  • aflibercept
  • Docetaxel
  • Receptors, Vascular Endothelial Growth Factor
  • Cisplatin