s-1-(combination) and Neuroendocrine-Tumors

Patients with advanced well-differentiated neuroendocrine tumors (NETs) who have bulky and/or symptomatic and/or rapidly progressive disease require chemotherapy treatment.. This review summarizes the accumulating evidence for treatment with fluorouracil-based chemotherapy in well-differentiated NETs. The main clinical studies, toxicity and predictors of fluorouracil- based chemotherapy regimens in well-differentiated NETs are discussed, along with the current issues, future research directions and therapeutic prospects.. Somatostatin analogs may control symptoms of hormone excess and tumor growth in patients with well-differentiated metastatic NETs, and biological therapies may improve progression-free survival for these patients. However, chemotherapy leads to higher objective response rates and symptom control by reducing tumor bulk. The low response rate and significant toxicities of conventional chemotherapy regimens limit their widespread use. Fortunately, some novel fluoropyrimidine-based treatment including fluorouracil, capecitabine, or S-1 based chemotherapy with or without antiangiogenic agents have been investigated in recent years. These treatments showed significant efficacy and less toxicity in pancreatic and non-pancreatic metastatic well-differentiated NETs. Additionally, non-pancreatic well-differentiated NETs have also achieved similar tumor response or survival comparable to pancreatic NETs. Moreover, some predictors of response to these treatment regimens have been evaluated.

Topics: Antimetabolites, Antineoplastic; Capecitabine; Disease-Free Survival; Drug Combinations; Drug Therapy, Combination; Fluorouracil; Humans; Neoplasm Staging; Neuroendocrine Tumors; Oxonic Acid; Pyrimidines; Tegafur; Treatment Outcome

Streptozocin (STZ) administration with or without other cytotoxic drugs remains a crucial chemotherapy for patients with advanced pancreatic neuroendocrine neoplasms (Pan-NENs). However, the therapeutic effects of combination treatment with weekly STZ and oral S-1 therapy (STS1) remain unknown. Therefore, the aim of this study was to evaluate the safety and clinical feasibility of STS1.. Twenty of 243 Pan-NEN patients were included in this retrospective study, all of whom had received STS1 for unresectable or distant metastatic diseases from November 2015 to January 2019. The maximum tumor shrinkage rate, time course of the tumor shrinkage rate, prognosis (progression-free survival and overall survival), and adverse events were evaluated.. The median age of the patients was 61.5 years and the median tumor size was 35 mm. The number of NET-G1, NET-G2, NET-G3, and NEC-G3 patients was 3, 13, 3, and 1, respectively. The median Ki-67 index and mitoses were 10.2% and 2/10 high-power fields, respectively. The overall objective response rate and disease control rate were 30% and 90%, respectively. The median maximum tumor reduction rate was 19%. The Ki-67 index and tumor size did not influence the tumor shrinkage rate. Progression-free survival after STS1 treatment was 19 months with no significant difference between NET-G1/G2 and NET-G3/NEC-G3 patients (p = 0.4). There was one case each of grade 3/4 toxicity, including general fatigue, hyperglycemia, and renal dysfunction. No serious myelosuppressive events are manifested.. STS1 treatment is an effective and safe therapeutic option for patients with advanced Pan-NEN.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Male; Middle Aged; Neuroendocrine Tumors; Oxonic Acid; Pancreatic Neoplasms; Progression-Free Survival; Retrospective Studies; Streptozocin; Tegafur

Both capecitabine alone and capecitabine in combination with temozolomide have activities against neuroendocrine tumors (NETs). However, the role of S-1 in NETs is still unknown. We performed a study to evaluate the safety and efficacy of the S-1/temozolomide (STEM) regimen in patients with locally advanced or metastatic NETs.. A retrospective review was conducted in 20 patients with locally advanced or metastatic NETs treated with the STEM regimen. Of the patients, 15 (75.00%) had failed 1 or more lines of treatment with somatostatin analogues, sunitinib, everolimus, anlotinib, or other chemotherapy regimens. The patients received S-1 at 40 mg/m2 orally twice daily on days 1-14 and temozolomide 200 mg orally once daily on days 10-14 of a 21-day cycle. The patients were followed up for evidence of object response, toxicity, and progression-free survival.. Response to treatment was assessed using RECIST 1.1. Eight patients (40.00%) achieved a partial response (PR), and another 8 (40.00%) had stable disease (SD). The clinical benefit rate (PR and SD) was 80.00%. The median progression-free survival was not achieved. Only 1 patient (5.00%) had grade 3 adverse events. Among the patients with NETs of different origins, 4 (40.00%) and 5 (50.00%) with pancreatic NETs attained PR and SD, respectively. Four (40.00%) and 3 patients (30.00%) with nonpancreatic NETs attained PR and SD, respectively.. The STEM regimen is exceptionally highly active and well tolerated in patients with locally advanced or metastatic NETs. Even in patients who showed disease progression with previous therapies, it is still highly active. In this 20-patient study, the regimen appeared to be similarly active in pancreatic endocrine tumors and nonpancreatic NETs.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neuroendocrine Tumors; Oxonic Acid; Retrospective Studies; Tegafur; Temozolomide; Treatment Outcome

A 41-year-old woman who had a pancreatic tail tumor and multiple liver tumors was referred to our hospital. The results of abdominal US, CT and MRI, and histopathological and immunohistochemical findings of the liver tumor biopsy revealed a pancreatic neuroendocrine tumor with excessively-advanced liver metastasis. We treated her with S-1/gemcitabine combination chemotherapy plus long-acting somatostatin analogue octreotide, which produced tumor stabilization and good quality of life for 7 months, and survival time of 15 months. Although the tumor was diagnosed as a poorly differentiated endocrine carcinoma, this therapy was suggested to be effective in this case.

Topics: Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Liver Neoplasms; Neuroendocrine Tumors; Octreotide; Oxonic Acid; Pancreatic Neoplasms; Tegafur

A 73-year-old man diagnosed as having pancreatic body cancer with multiple liver metastases was referred to our hospital. Since the patient preferred oral agents, S-1 monotherapy (4-week administration followed by 2-week interval) was started. The initial dose of S-1 was 80 mg, and gradually increased to 150 mg/day. There were no significant adverse events. The liver metastases disappeared and the pancreatic tumor was markedly reduced in size at the completion of 4 courses. Distal pancreatectomy was carried out at 7 months since his first visit. Pathological diagnosis was non-functioning well-differentiated neuroendocrine carcinoma (pT4, pN0, pM0, Stage IVa). He is alive without relapse 6 months after operation. S-1 might be a candidate for chemotherapy for this neuroendocrine tumor.

Topics: Aged; Antimetabolites, Antineoplastic; Drug Combinations; Humans; Liver Neoplasms; Male; Neoplasm Staging; Neuroendocrine Tumors; Oxonic Acid; Pancreatic Neoplasms; Positron-Emission Tomography; Tegafur; Tomography, X-Ray Computed