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Researchers from the University of Texas, Houston, recently evaluated the use of everolimus (RAD001) combined with octreotide long-acting repeatable (LAR) to treat patients who have advanced low- to intermediate-grade neuroendocrine tumors.
The study enrolled 60 patients: half had carcinoid tumors and half had islet-cell disease. Researchers assigned 30 patients to everolimus 5 mg per day and the remaining 30 patients to 10 mg per day plus octreotide LAR 30 mg every 28 days.
Clinicians noted a 20% intent-to-treat response rate. Overall, 13 patients achieved a partial response (22%), 42 had stable disease (70%), and 5 had progressive disease (8%). Median PFS was 60 weeks and, on average, was longer for patients with known stable disease on entry than for those who had progressive disease (74 wk vs 50 wk; P <.01).
Rates of survival were 83% for 1 year, 81% for 2 years, and 78% for 3 years. Of the 37 patients who had elevated chromogranin A, 26 (70%) attained normalization or more than a 50% reduction. The most common adverse effect was mild aphthous ulceration; at least 10% of patients experienced grade 3 or 4 of the following toxicities: fatigue (11%), diarrhea (11%), and hypophosphatemia (11%).
The treatment also appeared to correlate with a dose-dependent increase in lactate dehydrogenase. Patients whose level of lactate dehydrogenase did not increase at least 109 U/L by week 4 had markedly shorter PFS (38 wk vs 69 wk; P = .01).
Treatment with 5 mg or 10 mg of everolimus daily was well tolerated when combined with octreotide LAR, and researchers observed that the treatment demonstrated “promising antitumor activity.” Additional studies are being conducted to confirm these results.
Yao JC, Phan AT, Chang DZ, et al. Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study.
J Clin Oncol. 2008;26(26):4311-4318.