Phase II study of recombinant human endostatin in patients with advanced neuroendocrine tumors.
OBJECTIVE
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.


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.


CONCLUSIONS
Treatment with rhEndostatin did not result in significant tumor regression in patients with advanced neuroendocrine tumors.
Kulke
Matthew H
MH
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. matthew_kulke@dfci.harvard.edu
Bergsland
Emily K
EK
Ryan
David P
DP
Enzinger
Peter C
PC
Lynch
Thomas J
TJ
Zhu
Andrew X
AX
Meyerhardt
Jeffrey A
JA
Heymach
John V
JV
Fogler
William E
WE
Sidor
Carolyn
C
Michelini
Ann
A
Kinsella
Kate
K
Venook
Alan P
AP
Fuchs
Charles S
CS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D018278:Carcinoma, Neuroendocrine / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D043169:Endostatins / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D012646:Self Administration; D016019:Survival Analysis; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D043169:Endostatins; D011994:Recombinant Proteins