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Published on: February 12, 2017
Phase II study of recombinant human endostatin in patients with advanced neuroendocrine tumors
Matthew H Kulke1, Emily K Bergsland, David P Ryan
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. matthew_kulke@dfci.harvard.edu
Purpose:
Endostatin is a 20-kd proteolytic fragment of collagen XVIII that, in preclinical studies, has been shown to have antiangiogenic and antitumor activity. Both preclinical and human phase I studies of recombinant human endostatin (rhEndostatin) suggested activity in neuroendocrine tumors, which are known to be hypervascular. We therefore performed a multicenter phase II study of rhEndostatin in patients with carcinoid or pancreatic neuroendocrine tumors.
Patients And Methods:
Forty-two patients with advanced pancreatic endocrine tumors or carcinoid tumors were treated with rhEndostatin administered as a bid subcutaneous injection at a starting dose of 60 mg/m2/d. Steady-state trough levels were obtained after 6 weeks of therapy; patients who did not achieve a target therapeutic level of 300 ng/mL underwent dose escalation to 90 mg/m2/d. Patients were observed for evidence of toxicity, response, and survival.
Results:
rhEndostatin was associated with minimal toxicity. However, among 40 patients assessable for radiologic response, none experienced partial response to therapy, as defined by WHO criteria. The median steady-state trough level achieved after dose escalation was 331 ng/mL, within the postulated therapeutic range.
Conclusion:
Treatment with rhEndostatin did not result in significant tumor regression in patients with advanced neuroendocrine tumors.
Insights
Recombinant human endostatin (rhEndostatin) showed minimal toxicity in patients with advanced neuroendocrine tumors. However, the antiangiogenic therapy did not lead to significant tumor regression in this phase II study.
Area of Science:
- Oncology
- Pharmacology
Background:
- Endostatin, a collagen XVIII fragment, exhibits antiangiogenic and antitumor properties in preclinical models.
- Recombinant human endostatin (rhEndostatin) showed potential in early studies for neuroendocrine tumors.
Purpose of the Study:
- To evaluate the efficacy and safety of rhEndostatin in patients with advanced carcinoid or pancreatic neuroendocrine tumors.
- To assess the antiangiogenic potential of rhEndostatin in a clinical setting.
Main Methods:
- A multicenter phase II study involving 42 patients with advanced neuroendocrine tumors.
- rhEndostatin administered subcutaneously, with dose escalation to achieve target trough levels (300 ng/mL).
- Patients monitored for toxicity, radiologic response (WHO criteria), and survival.
Main Results:
- rhEndostatin demonstrated minimal toxicity in the patient cohort.
- No partial responses were observed among 40 assessable patients.
- Median steady-state trough levels reached 331 ng/mL after dose escalation, indicating therapeutic drug exposure.
Conclusions:
- rhEndostatin treatment did not achieve significant tumor regression in advanced neuroendocrine tumors.
- The study suggests limited clinical efficacy of rhEndostatin for this patient population despite adequate drug levels.