Dacarbazine or temozolomide, an oral analog of dacarbazine, showed activity against advanced pancreatic NETs when administered alone or in combination with other agents. Targeting pathways involved in angiogenesis, such as VEGFR TKI is also active in advanced pNETs. Endostatin is an endogenous angiogenesis inhibitor, rhEndostatin combined with chemotherapy prolonged overall survival compared with chemotherapy alone in advanced non-small cell lung cancer.
14 patients with histologically confirmed, locally advanced or metastatic pancreatic well-differentiated NETs with radiologic progression within the previous 12 months received the study regimen: Temozolomide was administered orally 150-200 mg/m2/d, d1-7. Dacarbazine and 5-FU were both administered intravenously at a dose of 250mg/m2/d and 500mg/m2/d respectively, d1-5. rhEndostatin was administered intravenously at a dose of 15mg/d, d1-14, repeated every 21 days. CT/MRI was performed at baseline and every 3 cycles after initiation of treatment. Radiologic response was classified according to RECIST 1.1 criteria.
Patients received a median of 6 treatment cycles (range, 2 to 8 cycles). Of the 14 patients, 6 patients received temozolomide and 8 received the DTIC + 5-FU combined with rhEndostatin. 5 patients used temozolomide as maintenance therapy, the median maintenance therapy cycles was 6 (range, 2 to 18 cycles). ORR was 43% (CR: 1 patient, PR: 5 patient), DCR was 86%, mPFS was 12 months, overall survival has not been reached. No grade 3/4 toxicity occurred.
rhEndostatin combined with temozolomide or darcarbazine-based chemotherapy was effective in treatment of advanced pNETs and was well tolerated.
Clinical trial identification
Legal entity responsible for the study
Peking Union Medical College Hospital, Ethic Committee
All authors have declared no conflicts of interest.