The combination of bevacizumab (Avastin) and temozolomide can be safely administered together in patients with advanced neuroendocrine tumors, and “the combination regimen appears promising for patients with pancreatic [neuroendocrine tumors],” according to results of a phase II study reported in the Journal of Clinical Oncology.
“Temozolomide was developed as a less toxic alternative to dacarbazine and has demonstrated activity in [neuroendocrine tumors] in both retrospective and prospective studies,” the investigators noted. Bevacizumab has shown activity when evaluated in advanced carcinoid tumors in two phase II studies. “Given the reported activity of both agents in carcinoid tumors and pancreatic [neuroendocrine tumors], we conducted a multi-institutional phase II study to assess the safety and efficacy of temozolomide given with bevacizumab in patients with advanced [neuroendocrine tumors],” the authors explained.
The study involved 34 patients, 19 with carcinoid tumors and 15 with pancreatic neuroendocrine tumors. The median age of patients was 60 years, and the male/female ratio was 19:15. All patients received temozolomide at 150 mg/m2 orally per day on days 1 through 7 and days 15 through 21, together with bevacizumab at a dose of 5 mg/kg/d intravenously on days 1 and 15 of each 28-day cycle, along with prophylaxis against Pneumocystis carinii and varicella zoster.
“Although the overall radiographic response rate was 15% (5 of 34), response rates differed between patients with pancreatic [neuroendocrine tumors] (33%; 5 of 15) and those with carcinoid tumors (0 of 19),” the researchers reported. “The median progression-free survival was 11.0 months (14.3 months for pancreatic [neuroendocrine tumors] vs 7.3 months for carcinoid tumors). The median overall survival was 33.3 months (41.7 months for pancreatic [neuroendocrine tumors] vs 18.8 months for carcinoid tumors).”
Grade 3 to 4 toxicities included lymphopenia (53%) and thrombocytopenia (18%). “The most common nonhematologic adverse events were fatigue (76%), nausea (68%), vomiting (65%), anorexia (44%), constipation (32%), and diarrhea (29%). Most toxicities were relatively mild,” the authors stated. “Studies evaluating the relative contributions of these two agents to the observed antitumor activity are warranted,” they concluded.■
Chan JA, et al: J Clin Oncol. July 9, 2012 (early release online).