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

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.

Figures

Figure 1

Kaplan–Meier estimates of survival for all patients by treatment groups. (a) Progression-free survival. (b) Overall survival. CI, confidence interval; HR, hazard ratio; PFS, progression-free survival; OS, overall survival.

Figure 2

Endostatin expression and antiangiogenic assessments. (a) Serum endostatin concentration during treatment; Pretreatment and posttreatment assessments of (b) immunohistochemical staining of endostatin in the biopsies of the E10A group. Bar = 100 µm; (c) H score of endostatin in the biopsies of the E10A group; (d) immunohistochemical staining of CD34 (marker of vascular formation). Bar = 100 µm; (e) microvessel density of tumors; (f) blood flow volume in tumors (evaluated by dynamic contrast-enhanced ultrasound); (g) echo-power of blood flow volume in the tumor of patient No. 01C075; (h) echo-power peaks of blood flow volume in eight tumors.

Figure 3

Leukocyte infiltration in the E10A group tumor samples. Pretreatment and posttreatment immunohistochemical staining of (a) CD3+ T cells and (b) CD19+ B cells. Bar = 100 µm.