Kocha, Walter

AbstractIntroduction.The incidence of colorectal neuroendocrine tumors (NETs) is increasing, and patients with this disease have particularly poor prognoses. Treatment options are limited, and survival times have not improved in the past decade.Methods.A post hoc analysis of the efficacy and tolerability of everolimus plus octreotide long-acting repeatable (LAR) was conducted in patients with colorectal NETs enrolled in the phase III RAD001 in Advanced Neuroendocrine Tumors, Second Trial (RADIANT-2) study. The primary endpoint (progression-free survival [PFS]), secondary endpoints (including objective response rate), and safety were assessed.Results.Patients with colorectal NETs receiving everolimus plus octreotide LAR had a significantly longer median PFS (29.9 months; n = 19) than did those receiving placebo plus octreotide LAR (6.6 months; n = 20). Everolimus plus octreotide LAR treatment also significantly reduced the risk for disease progression (hazard ratio: 0.34; 95% confidence interval: 0.13–0.89; p = .011). Although no objective responses were observed, tumor shrinkage was more frequently noted in the everolimus plus octreotide LAR arm than in the placebo plus octreotide LAR arm (67% vs. 37%, respectively). The combination of everolimus plus octreotide LAR was generally well tolerated by patients with colorectal NETs; rash and stomatitis were the most commonly reported adverse events.Conclusions.Everolimus plus octreotide LAR treatment had significant benefits and improved outcomes for patients with advanced colorectal NETs compared with placebo plus octreotide LAR treatment. Results of this exploratory analysis are consistent with those reported from the RADIANT-2 primary analysis. These findings support additional investigations of everolimus plus octreotide LAR in patients with colorectal NETs.

Purpose We update Radiation Therapy Oncology Group trial 8911 (USA Intergroup 113), a comparison of chemotherapy plus surgery versus surgery alone for patients with localized esophageal cancer. The relationship between resection type and between tumor response and outcome were also analyzed. Patients and Methods The chemotherapy group received preoperative cisplatin plus fluorouracil. Outcome based on the type of resection (R0, R1, R2, or no resection) was evaluated. The main end point was overall survival. Disease-free survival, relapse pattern, the influence of postoperative treatment, and the relationship between response to preoperative chemotherapy and outcome were also evaluated. Results Two hundred sixteen patients received preoperative chemotherapy, 227 underwent immediate surgery. Fifty-nine percent of surgery only and 63% of chemotherapy plus surgery patients underwent R0 resections (P = .5137). Patients undergoing less than an R0 resection had an ominous prognosis; 32% of patients with R0 resections were alive and free of disease at 5 years, only 5% of patients undergoing an R1 resection survived for longer than 5 years. The median survival rates for patients with R1, R2, or no resections were not significantly different. While, as initially reported, there was no difference in overall survival for patients receiving perioperative chemotherapy compared with the surgery only group, patients with objective tumor regression after preoperative chemotherapy had improved survival. Conclusion For patients with localized esophageal cancer, whether or not preoperative chemotherapy is administered, only an R0 resection results in substantial long-term survival. Even microscopically positive margins are an ominous prognostic factor. After a R1 resection, postoperative chemoradiotherapy therapy offers the possibility of long-term disease-free survival to a small percentage of patients.