Streptozocin chemotherapy for advanced/metastatic well-differentiated neuroendocrine tumors: an analysis of a multi-center survey in Japan

Abstract

BackgroundNeuroendocrine tumors (NETs) are believed to be relatively rare and to follow a generally indolent course. However, liver metastases are common in NET patients and the outcome of NET liver metastasis is poor. In Western countries, streptozocin (STZ) has been established as a first-line anticancer drug for unresectable NET; however, STZ cannot be used in daily practice in Japan. The aim of the present study was to determine the status of STZ usage in Japan and to evaluate the effectiveness and safety of STZ chemotherapy in Japanese NET patients.MethodsA retrospective multi-center survey was conducted. Five institutions with experience performing STZ chemotherapy participated in the study. The patient demographics, tumor characteristics, context of STZ chemotherapy, and patient outcome were collected and assessed.ResultsFifty-four patients were enrolled. The main recipients of STZ chemotherapy were middle-aged patients with pancreatic NET and unresectable liver metastases. The predominant regimen was the weekly/bi-weekly intravenous administration of STZ combined with other oral anticancer agents. STZ monotherapy was used in one-fourth of the patients. The median progression-free and overall survival periods were 11.8 and 38.7 months, respectively, and sustained stable disease was obtained in some selected patients. The adverse events profile was mild and tolerable.ConclusionsOur survey showed the clinical benefit and safety of STZ therapy for Japanese patients with unresectable NET. Therefore, we recommend that STZ, which is the only cytotoxic agent available against NET, should be used in daily practice in Japan.Electronic supplementary materialThe online version of this article (doi:10.1007/s00535-014-1006-3) contains supplementary material, which is available to authorized users.

Successful Salvage Chemotherapy with Streptozocin in a Patient with Mediastinal Atypical Carcinoid Tumor Who Had Relapsed after Various Prior Therapies

“…With regard to pancreatic NET, a randomized trial indicated the superiority of STZ combined with 5-FU as compared to STZ monotherapy [ 9 , 14 , 15 ]. The toxicities in STZ-based chemotherapy were well tolerated in previous reports [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. Although the present case was treated successfully with STZ monotherapy and there were no specific toxicities, it was necessary to combine some cytotoxic agents with STZ for additive clinical benefit.…”

“…Several studies in patients with NET of the pancreas and digestive tract indicated response rates to chemotherapy with STZ in combination with 5-FU or doxorubicin of 27.7–42.0% [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. To our knowledge, there have been no reports focusing on the efficacy of STZ-based chemotherapy in lung NET.…”

“…Streptozocin (STZ) has been used for up to 30 years as a single agent or in combination therapy for the treatment of NETs in the pancreas and digestive tracts [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. A study pooling reports of STZ monotherapy showed a response rate of 42% [ 8 ].…”

“…A study pooling reports of STZ monotherapy showed a response rate of 42% [ 8 ]. Although there have been careful clinical evaluations of the usefulness of STZ in pancreatic NET [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ], little information is available regarding the clinical benefit in patients with lung NET [ 5 , 10 ]. We encountered a case of metastatic and relapsed mediastinal AC tumor associated with multiple endocrine neoplasia type 1.…”

O 6-Methylguanine DNA Methyltransferase and Glucose Transporter 2 in Foregut and Hindgut Gastrointestinal Neuroendocrine Neoplasms

“…Therefore, STZ is currently used as a cytotoxic agent for treating pancreatic NET (PanNETs) and GI-NETs. However, its response rate is 40.0% for PanNETs and only 25.0% for GI-NETs [6]. In addition, signi cant improvement of progression-free survival of STZ has not necessarily been established in patients with GI-NETs compared to those with PanNETs, especially in foregut and hindgut NETs [5,7,8].…”