Multi-center clinical evaluation of streptozocin-based chemotherapy for advanced pancreatic neuroendocrine tumors in Japan: focus on weekly regimens and monotherapy

Shibuya, Hitoshi; Hijioka, Susumu; Sakamoto, Yasunari; Ito, Tetsuhide; Ueda, Keijiro; Komoto, Izumi; Kobayashi, Noritoshi; Kudo, Akira; Yasuda, Hiroaki; Miyake, Hayato; Arita, Junichi; Kiritani, Sho; Ikeda, Masafumi; Imaoka, Hiroshi; Ueno, Makoto; Kobayashi, Satoshi; Furuta, Mitsuhiro; Nagashio, Yoshikuni; Murohisa, Gou; Aoki, Taku; Matsumoto, Shigemi; Motoya, Masayo; Azemoto, Nobuaki; Itakura, Jun; Horiguchi, Shigeru; Yogi, Tatsuji; Kawagoe, Tetsuro; Miyaoka, Youichi; Imamura, Fumito; Senju, Michio; Arioka, Hitoshi; Hara, Kazuo; Imamura, Masayuki; Okusaka, Takuji

doi:10.1007/s00280-018-3656-y

Cited by 27 publications

(20 citation statements)

References 29 publications

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“…Previously published series reporting on treatment and outcomes for G3 NET are shown in Table 4. Median overall survival of 19 months in our cohort was shorter when compared with most previously published series of G3 NET 5,6,8,9,[13][14][15][23][24][25] (Table 4). Potentially contributing to this is the lower proportion of patients with SSR avid disease and the high proportion of tumours of unknown primary amongst our cohort compared with prior publications 6,8,9 .…”

Section: Discussioncontrasting

confidence: 61%

Well-differentiated gastroenteropancreatic G3 NET: findings from a large single centre cohort

Lithgow

Venkataraman

Hughes

et al. 2021

Sci Rep

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Neuroendocrine neoplasms are known to have heterogeneous biological behavior. G3 neuroendocrine tumours (NET G3) are characterized by well-differentiated morphology and Ki67 > 20%. The prognosis of this disease is understood to be intermediate between NET G2 and neuroendocrine carcinoma (NEC). Clinical management of NET G3 is challenging due to limited data to inform treatment strategies. We describe clinical characteristics, treatment, and outcomes in a large single centre cohort of patients with gastroenteropancreatic NET G3. Data was reviewed from 26 cases managed at Queen Elizabeth Hospital, Birmingham, UK, from 2012 to 2019. Most commonly the site of the primary tumour was unknown and majority of cases with identifiable primaries originated in the GI tract. Majority of cases demonstrated somatostatin receptor avidity. Median Ki67 was 30%, and most cases had stage IV disease at diagnosis. Treatment options included surgery, somatostatin analogs (SSA), and chemotherapy with either platinum-based or temozolomide-based regimens. Estimated progression free survival was 4 months following initiation of SSA and 3 months following initiation of chemotherapy. Disease control was observed following treatment in 5/11 patients treated with chemotherapy. Estimated median survival was 19 months; estimated 1 year survival was 60% and estimated 2 year survival was 13%. NET G3 is a heterogeneous group of tumours and patients which commonly have advanced disease at presentation. Prognosis is typically poor, though select cases may respond to treatment with SSA and/or chemotherapy. Further study is needed to compare efficacy of different treatment strategies for this disease.

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Section: Discussioncontrasting

confidence: 61%

Well-differentiated gastroenteropancreatic G3 NET: findings from a large single centre cohort

Lithgow

Venkataraman

Hughes

et al. 2021

Sci Rep

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“…The combination of streptozotocin + doxorubicin had a significant advantage in terms of objective response rate (ORR) and survival over streptozotocin + 5-fluorouracil (ORR: 69% vs. 45%, p = 0.05; median overall survival [mOS] 2.2 vs. 1.4 years; p = 0.004) [ 12 ]. This high ORR with streptozotocin was not reproducible later in retrospective series [ 13 , 14 , 15 , 16 ]. In a retrospective study on 110 patients with metastatic panNETs, Ki-67 > 5% was the only predictive marker of an objective response with streptozotocin [ 16 ].…”

Section: Well-differentiated G1/g2 Pannetsmentioning

confidence: 96%

“…This high ORR with streptozotocin was not reproducible later in retrospective series [ 13 , 14 , 15 , 16 ]. In a retrospective study on 110 patients with metastatic panNETs, Ki-67 > 5% was the only predictive marker of an objective response with streptozotocin [ 16 ]. Streptozotocin renal toxicity does not appear to be a major cause of treatment discontinuation [ 17 ].…”

Section: Well-differentiated G1/g2 Pannetsmentioning

confidence: 96%

Medical Treatment of Advanced Pancreatic Neuroendocrine Neoplasms

Dermine

Barré

Dhooge

et al. 2020

JCM

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Pancreatic neuroendocrine neoplasms (panNENs) are relatively rare but their incidence has increased almost sevenfold over the last four decades. Neuroendocrine neoplasms are classified according to their histologic differentiation and their grade. Their grade is based on their Ki-67 proliferation index and mitotic index. Their prognosis is highly variable according to these elements and treatments also vary according to their classification. Surgery is the only curative treatment for localized and advanced panNENs and offers a better prognosis than non-surgical treatments. In the case of an advanced panNEN without the possibility of resection and/or ablation, medical treatment remains the cornerstone for improving survival and preserving quality-of-life. PanNENs are considered as chemosensitive tumors, unlike midgut neuroendocrine tumors. Thus, panNENs can be treated with chemotherapy, but targeted therapies and somatostatin analogs are also treatment options. The scarcity and heterogeneity of NENs make their management difficult. The present review aims to clarify the medical treatments currently available for advanced panNENs, based on their characteristics, and to propose a treatment algorithm.

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“…In Japan, STZ is frequently used not only daily regimen but also weekly regimen ( 51 , 52 ). This has an advantage to be able to give treatment in an outpatient.…”

Section: Standard and Promising Therapies For Unresectable/recurrent Gep-nets And Necsmentioning

confidence: 99%

Current status of medical treatment for gastroenteropancreatic neuroendocrine neoplasms and future perspectives

Hijioka¹,

Morizane²,

Ikeda

et al. 2021

Japanese Journal of Clinical Oncology

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Neuroendocrine neoplasms (NENs) constitute a heterogeneous group of tumors. In this review, we summarize the results of various clinical trials that have been conducted to investigate the efficacy and safety of various therapeutic options for NENs. Based on the encouraging results obtained from these trials, various therapeutic options have been established for the treatment of NENs, including somatostatin analogs (SSAs), molecularly targeted drugs and cytotoxic agents. In addition, peptide receptor radionucleotide therapy has recently been evaluated for the treatment of various NENs. We also discuss the approach for selecting the appropriate drugs and sequence of treatment with the various drug classes, as recommended by different treatment guidelines. Finally, we discuss the scope for future research in this field, especially into the merits of combination therapy with molecularly targeted drugs plus SSAs, along with ongoing studies.

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Multi-center clinical evaluation of streptozocin-based chemotherapy for advanced pancreatic neuroendocrine tumors in Japan: focus on weekly regimens and monotherapy

Abstract: The effects of weekly STZ monotherapy on pNET are comparable to those previously reported and the toxicity profile was acceptable. Ki67 > 5% was the sole predictive marker of an objective response.

Cited by 27 publications

References 29 publications

Well-differentiated gastroenteropancreatic G3 NET: findings from a large single centre cohort

Well-differentiated gastroenteropancreatic G3 NET: findings from a large single centre cohort

Medical Treatment of Advanced Pancreatic Neuroendocrine Neoplasms

Current status of medical treatment for gastroenteropancreatic neuroendocrine neoplasms and future perspectives

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