Clinical study on the recombinant human endostatin regarding improving the blood perfusion and hypoxia of non-small-cell lung cancer.

OBJECTIVE: To observe the dynamic changes of blood perfusion and hypoxic status with CT perfusion imaging and hypoxia imaging in patients of non-small-cell lung cancer (NSCLC) who were treated with recombinant human endostatin (RHES). METHODS: Fifteen previously untreated patients with histologically or cytologically confirmed NSCLC were enrolled. They were randomly divided into research group (n=10) and negative control group (n=5). The patients of the research group continuously used RHES for ten days, and simultaneously had CT perfusion imaging and hypoxia imaging performed on days 1, 5 and 10, respectively. The remaining 5(control) only had CT perfusion imaging and hypoxia imaging, without using RHES, on days 1, 5 and 10, respectively. According to the above results, we could obtain a "time window" during which RHES improves blood perfusion and hypoxia of lung cancer. RESULTS: In the research group, after using RHES, capillary permeability surface (PS) and tumour to normal tissue (T/N) decreased at first, and then increased. Their lowest points occurred on about the fifth day with statistical significance compared with the first day (T/N, p=0.00; PS, p<0.01). Blood flow (BF) was first increased and then decreased. Its highest point occurred on about the fifth day with statistical significance compared with the first and tenth day (all p<0.01). The PS, BF and T/N peaked on the fifth day in the research group with statistical significance compared with the negative control group as well (all p<0.01). The above results suggested that RHES's "time window" was within about one week after administration. CONCLUSION: RHES's "time window" is within about one week after administration, which provides an important experimental basis for combining RHES with radiotherapy in human tumours.

Preliminary clinical study of weekly recombinant human endostatin as a hypoxic tumour cell radiosensitiser combined with radiotherapy in the treatment of NSCLC.

OBJECTIVE: To investigate the clinical effects and adverse effects of weekly recombinant human endostatin (RHES) as a hypoxic tumour cell radiosensitiser combined with radiotherapy in the treatment of non-small-cell lung cancer (NSCLC). METHODS: Fifty hypoxia-positive cases of pathology-diagnosed NSCLC (stage I-III) were randomly divided into a RHES+radiotherapy group (25 cases) and a radiotherapy alone group (25 cases). Intensity-modulated radiotherapy (IMRT) with a total dose of 60 Gy/30F/6W was adopted in the two groups. Target area included primary foci and metastatic lymph nodes. In the RHES+radiotherapy group, RHES (15 mg/day) was intravenously given during the first week. The therapeutic effects and adverse reactions were evaluated after treatment. RESULTS: In the RHES+radiotherapy and radiotherapy alone groups, the total effective rates (CR+PR) were 80% and 44% (χ(2)=6.87, p=0.009), respectively. The one-year and two-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 median progression-free survival was (21.1±0.97) and (16.5±0.95) months, respectively. The one-year and two-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: RHES combined with radiotherapy within the first week has better short-term therapeutic effects and local control rate, and no severe adverse reactions in treatment of NSCLC. However, it failed to significantly improve the one-year and two-year overall survival rates.