Effect of recombinant human endostatin on radiosensitivity in patients with non-small-cell lung cancer

Int J Radiat Oncol Biol Phys. 2012 Jul 15;83(4):1272-7. doi: 10.1016/j.ijrobp.2011.09.050. Epub 2011 Nov 16.

Abstract

Purpose: To observe the effects of recombinant human endostatin (RHES) on the radiosensitivity of non-small cell lung cancer (NSCLC).

Methods and materials: First, 10 hypoxia-positive cases of pathology-diagnosed NSCLC selected from 15 patients were used to determine the normalization window, a period during which RHES improves NSCLC hypoxia. Second, 50 hypoxia-positive cases of pathology-diagnosed NSCLC (Stages I-III) were randomly divided into a RHES plus radiotherapy group (25 cases) and a radiotherapy-alone group (25 cases). Intensity = modulated radiotherapy with a total dose of 60 Gy in 30 fractions for 6 weeks was adopted in the two groups. The target area included primary foci and metastatic lymph nodes. In the RHES plus radiotherapy group, RHES (15 mg/day) was intravenously given during the normalization window.

Results: After RHES administration, the tumor-to=normal tissue radioactivity ratio and capillary permeability surface were first decreased and then increased, with their lowest points on the fifth day compared with the first day (all p < 0.01). Blood flow was first increased and then decreased, with the highest point on the fifth day, compared with the first and tenth day (all p < 0.01). In the RHES plus radiotherapy group and the radiotherapy-alone group, the total effective rates (complete response plus partial response) were 80% and 44% (p = 0.009), respectively. The median survival times were 21.1 ± 0.97 months and 16.5 ± 0.95 months (p = 0.004), respectively. The 1-year and 2-year local control rates were 78.9 ± 8.4% and 68.1 ± 7.8% (p = 0.027) and 63.6 ± 7.2% and 43.4 ± 5.7% (p = 0.022), respectively. The 1-year and 2-year overall survival rates were 83.3 ± 7.2% and 76.6 ± 9.3% (p = 0.247) and 46.3 ± 2.4% and 37.6 ± 9.1% (p = 0.218), respectively.

Conclusion: The RHES normalization window is within about 1 week after administration. RHES combined with radiotherapy within the normalization window has better short-term therapeutic effects and local control rates and no severe adverse reactions in the treatment of NSCLC, but it failed to significantly improve the 1-year and 3-year overall survival rates.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood supply
  • Adenocarcinoma / mortality
  • Adenocarcinoma / therapy
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Capillary Permeability / drug effects
  • Capillary Permeability / physiology
  • Capillary Permeability / radiation effects
  • Carcinoma, Non-Small-Cell Lung / blood supply
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Carcinoma, Squamous Cell / blood supply
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / therapy
  • Cell Hypoxia / drug effects*
  • Endostatins / therapeutic use*
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / analysis
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / mortality
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Radiation Tolerance / drug effects*
  • Radiotherapy, Intensity-Modulated*
  • Recombinant Proteins / therapeutic use
  • Time Factors

Substances

  • Antineoplastic Agents
  • Endostatins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Recombinant Proteins