Curative Effect Study of Endostatin Combined With Chemoradiotherapy to Non-small-cell Lung Cancer

Phase I/II Clinical Trial of Recombinant Human Endostatin in Combination With Concurrent Chemo-Radiotherapy in the Patients With Unresectable Stage III Non-small-Cell Lung Cancer

To evaluate the efficacy and safety of Endostar combined with concurrent chemo-radiotherapy (CCRT) in patients with unresectable stage III non-small-cell lung cancer (NSCLC).

OBJECTIVES:

Primary:To assess the treatment response rate (RR) of Endostar in combination with CCRT

Secondary

• The progression-free survival (PFS)
• The overall survival(OS).
• The failed treatment modality.
• The toxicity of this regimen.

OUTLINE CCRT:Patients receive chemotherapy comprising Docetaxel(65mg/m2,iv gtt duration>1h) and Cisplatin(65mg/m2,concurrent hydration) on days 1 and 29 and at least 3 hours after chemotherapy undergo concurrent 3D-CRT five days a week for total dose 60-66Gy.

Endostatin:Patients receive Endostatin 7.5mg/m2 daily by iv gtt up to 7 days consecutively 1 week before radiotherapy and repeat every 2 weeks.

Patients are seen in follow-up every 3 months for 2 years and then every 6 months thereafter. Physical examination and CT scans of the thorax and upper abdomen are performed routinely.

Inclusion Criteria:

• 18 years of age

  • untreated pathologically confirmed inoperable stage IIIA or IIIB NSCLC
  • weight loss of less than 10% in the past 6 months
  • performance status (PS) of 0 to 1
  • forced vital capacity in 1 second (FEV1) higher than 0.8 L
  • measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST).
  • absolute neutrophil count (ANC) of ≥ 1500/μL
  • hemoglobin ≥ 10 mg/dL
  • platelet ≥ 100,000/μL
  • serum creatinine ≤ 1.25 times of upper limit of normal (ULN)
  • calculated creatinine clearance (CrCl) of ≥ 60 ml/min
  • bilirubin 1.5×ULN
  • AST and ALT less than 2.5×ULN
  • alkaline phosphatase less than 5×ULN.

Exclusion Criteria:

• active infection
• history of significant cardiac disease (unstable angina, congestive heart failure, myocardial infarction within the previous 6 months, ventricular arrhythmias)
• malnutrition (loss of ≥ 20% of the original body weight)
• sensor or motor neuropathy > grade I
• second primary malignancy, except for non-melanoma skin cancer
• psychiatric illness or social situation that would preclude study compliance
• pregnant or lactating women
• preexisting bleeding diatheses or coagulopathy
• Prior chemotherapy,chest irradiation therapy, or therapy directed at the epidermal growth factor receptor pathway