Multicenter randomized phase 2 clinical trial of a recombinant human endostatin adenovirus in patients with advanced head and neck carcinoma

Mol Ther. 2014 Jun;22(6):1221-1229. doi: 10.1038/mt.2014.53. Epub 2014 Mar 25.

Abstract

A randomized, open-label, phase 2, multicenter clinical trial was conducted to evaluate the efficacy and safety of the addition of a recombinant human endostatin adenovirus (E10A) to cisplatin and paclitaxel in patients with advanced head and neck squamous cell carcinoma or nasopharyngeal carcinoma. Patients with locally advanced or metastatic head and neck squamous cell carcinoma or nasopharyngeal carcinoma not suitable for operation or radiotherapy were randomly assigned to receive E10A plus chemotherapy every 3 weeks for a maximum of six cycles or to receive chemotherapy only. One hundred and thirty-six eligible patients were randomly assigned. The addition of E10A did not significantly improve the objective response rate (29.9 versus 39.7%, P = 0.154). However, patients who received endostatin had longer progression-free survival (7.03 versus 3.60 months, P = 0.006; hazard ratio: 0.55). The combination of E10A with chemotherapy benefited prior chemotherapy-treated patients and those who received three to four treatment cycles (6.50 versus 3.43 months, P = 0.003; 8.27 versus 4.27 months, P = 0.018; respectively). The overall disease control rate significantly increased from 80.6% in the control group to 92.6% in the test group (P = 0.034). Except for fever, no adverse events were associated with the E10A treatment. In summary, E10A plus chemotherapy is a safe and effective therapeutic approach in patients with advanced head and neck squamous cell carcinoma or nasopharyngeal carcinoma.

Trial registration: ClinicalTrials.gov NCT00634595.

Publication types

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

MeSH terms

  • Adenoviridae / genetics
  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Carcinoma, Squamous Cell / virology
  • Cisplatin / adverse effects*
  • Combined Modality Therapy
  • Endostatins / adverse effects*
  • Genetic Therapy
  • Genetic Vectors / administration & dosage
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / therapy*
  • Head and Neck Neoplasms / virology
  • Humans
  • Male
  • Middle Aged
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / therapy*
  • Nasopharyngeal Neoplasms / virology
  • Neoplasm Metastasis / pathology
  • Neoplasm Metastasis / therapy*
  • Neoplasm Recurrence, Local
  • Paclitaxel / adverse effects
  • Recombinant Proteins / adverse effects
  • Squamous Cell Carcinoma of Head and Neck
  • Survival Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents
  • Endostatins
  • Recombinant Proteins
  • Paclitaxel
  • Cisplatin

Associated data

  • ClinicalTrials.gov/NCT00634595