Neoadjuvant Capecitabine/Temozolomide for Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors

Abstract

Objectives The combination chemotherapy regimen capecitabine/temozolomide (CAPTEM) is efficacious for metastatic well-differentiated pancreatic neuroendocrine tumors (PNETs), but its role in the neoadjuvant setting has not been established. Methods The outcomes of all patients with locally advanced or resectable metastatic PNETs who were treated with neoadjuvant CAPTEM between 2009 and 2017 at 2 high-volume institutions were retrospectively reviewed. Results Thirty patients with locally advanced PNET (n = 10) or pancreatic neuroendocrine hepatic metastases (n = 20) received neoadjuvant CAPTEM. Thirteen patients (43%) exhibited partial radiographic response (PR), 16 (54%) had stable disease, and 1 (3%) developed progressive disease. Twenty-six (87%) patients underwent resection (pancreatectomy [n = 12], combined pancreatectomy and liver resection [n = 8], or major hepatectomy alone [n = 6]); 3 (18%) declined surgery despite radiographic PR, and 1 (3%) underwent aborted pancreatoduodenectomy. Median primary tumor size was 5.5 cm, and median Ki-67 index was 3.5%. Rates of PR were similar across tumor grades (P = 0.24). At median follow-up of 49 months, median progression-free survival was 28.2 months and 5-year overall survival was 63%. Conclusions Neoadjuvant CAPTEM is associated with favorable radiographic objective response rates for locally advanced or metastatic PNET and may facilitate selection of patients appropriate for surgical resection.

Surgery after sunitinib administration to improve survival of patients with advanced pancreatic neuroendocrine neoplasms

“… 15 Another one‐arm study involving 30 patients with locally advanced or resectable metastases who received capecitabine or temozolomide chemotherapy illustrated patient prognoses after administration of chemotherapy, although four patients could not undergo surgery. 16 Another study involving 67 patients with liver metastases who underwent R0/1 surgeries illustrated the prognoses of 27 and 40 patients who received FAS therapy followed by surgery compared with surgery alone, respectively. 17 The present study involved 106 Pan‐NEN patients with locally advanced and/or liver metastases who were administered sunitinib and reported the prognosis of 31 patients who underwent surgery following sunitinib and 75 patients who did not undergo surgery.…”

“…20,21 The median Ki-67 index was 12% and mitosis was 2/10 HPFs, and the surgical indications for each type of liver metastases were similar to those reported in previous studies that illustrated neoadjuvant chemotherapy for Pan-NEN. [15][16][17] With the background data, the 5-y OS of the resected and nonresected groups were 89% and 14%, respectively (Figure 2). Thus, the present study demonstrated that patients who underwent surgery after sunitinib treatment had much better 5-y OS rates than those who did not undergo surgery (P < .001), although previous studies on aggressive surgery for advanced or metastatic Pan-NENs without preoperative chemotherapy indicated that the 5-y OS rates were 60-80%.…”

“…In recent years, small retrospective studies have compared chemotherapy or surgery independently with chemotherapy followed by surgery in Pan‐NEN patients with distant metastases and/or unresectable locally advanced tumors 15–17 . Moreover, no study has used molecular‐targeted drugs such as sunitinib.…”

“…In recent years, small retrospective studies have compared chemotherapy or surgery independently with chemotherapy followed by surgery in Pan‐NEN patients with distant metastases and/or unresectable locally advanced tumors. 15 , 16 , 17 Moreover, no study has used molecular‐targeted drugs such as sunitinib. In this study, we aimed to assess the prognosis of Pan‐NEN patients with distant metastases and/or unresectable locally advanced tumors who received sunitinib as a primary regimen before surgery.…”

Neuroendocrine liver metastases treatment strategies: a viewpoint

“…Pre-operative 5-fluorouracil, doxorubicin and streptozocin regimen has been associated with improved OS compared to surgery alone among patients with advanced synchronous pancreatic NELM (1). The orally-available regimen capecitabine and temozolomide (CAPTEM) is associated with favorable radiographic objective response rates for locally advanced or metastatic pancreatic NENs and may facilitate selection of patients appropriate for surgical resection (6). For what matters the potential role of PRRT in the neoadjuvant setting little is known in the specific context of NELM.…”