Concomitant 177Lu-DOTATATE and Capecitabine Therapy in Patients With Advanced Neuroendocrine Tumors A Long-term-Outcome, Toxicity, Survival, and Quality-of-Life Study

Purpose: The purpose of this study was to evaluate the outcome, toxicity, survival, and quality of life in patients with advanced neuroendocrine tumors. Methods: One hundred sixty-seven patients were enrolled in the study. All patients underwent baseline Ga-68-DOTANOC PET/CT scans. Lu-177-DOTATATE therapy was administered quarterly along with oral capecitabine therapy in group 1 patients (n = 88), whereas group 2 patients (n = 79) were treated only with Lu-177-DOTATATE. Hematologic, kidney function, liver function tests and chromogranin A levels were recorded before and after therapy at 2-week, 4-week, and 3-month intervals. Biochemical and morphological responses were assessed with the trend in chromogranin A levels and Response Evaluation Criteria in Solid Tumors 1.1 criteria, respectively. Results: There was no significant difference in the hemoglobin levels after Lu-177-DOTATATE therapy (P = 0.4892). In most patients, there was a decrease in the platelet levels; however, all the patients had platelet counts greater than 100,000/mu L with no platelet toxicity. There was no toxicity related to leukocytes. Two patients showed renal insufficiencies. No hepatotoxicity was observed in any of the patients. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, in group 1 patients, the response was partial response in 34% of the patients, stable disease in 50.2%, and progressive disease in 6.8% versus partial response in 6.3%, stable disease in 60.9%, and progressive disease in 26.5% among group 2 patients. The median overall survival (OS) and progression-free survival (PFS) was not reached in group 1 patients. The median OS and PFS in group 2 patients were 48 months. Ki-67 tumor proliferation index was significantly associated with increased risk of disease progression. Conclusions: Addition of capecitabine therapy with Lu-177-DOTATATE therapy lengthens the OS and PFS. Patients with aggressive disease may benefit from this synergetic therapeutic approach.