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

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Purpose: Streptozocin (STZ) is a key agent for treating advanced pancreatic neuroendocrine tumors (pNET). Most STZ regimens for pNET are daily and also include 5-fluorouracil (5FU), whereas STZ monotherapy and weekly regimens have also been applied in daily practice in Japan. The present study aimed to evaluate responses to weekly regimens and to STZ monotherapy, and to identify a predictive marker of a response to STZ. Methods: Clinical data regarding STZ-based chemotherapy for pNET were collected between 2015 and 2017 at 25 facilities. We analyzed the effects, safety, progression-free survival (PFS), and factors that correlate with responses to STZ. Results: The overall objective response rate (ORR) of 110 patients who underwent STZ-based chemotherapy (monotherapy, 81.8%; weekly regimen 46.4%) was 21.8%, and PFS was 9.8 months. The ORR of weekly vs. daily regimens was 21.6 vs. 22.0% (P = 1.000), and that of monotherapy vs. combination therapy was 21.1 vs. 25.0% (P = 0.766). A Ki67 proliferation index (Ki67) of > 5% was a predictive marker of a response to STZ (P = 0.017), whereas regimen type, mono- or combination therapy, treatment line and liver tumor burden were not associated with responses. The frequencies of Grade ≥ 3 nausea and hematological adverse events were significantly lower for monotherapy than combination therapy (P = 0.032). Conclusions: 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.

Original languageEnglish
Pages (from-to)661-668
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume82
Issue number4
DOIs
Publication statusPublished - Oct 1 2018

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Keywords

  • Ki67 proliferation index
  • Monotherapy
  • Pancreatic neuroendocrine tumor
  • Prognostic factor
  • Streptozocin

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Shibuya, H., Hijioka, S., Sakamoto, Y., Ito, T., Ueda, K., Komoto, I., Kobayashi, N., Kudo, A., Yasuda, H., Miyake, H., Arita, J., Kiritani, S., Ikeda, M., Imaoka, H., Ueno, M., Kobayashi, S., Furuta, M., Nagashio, Y., Murohisa, G., ... Okusaka, T. (2018). Multi-center clinical evaluation of streptozocin-based chemotherapy for advanced pancreatic neuroendocrine tumors in Japan: focus on weekly regimens and monotherapy. Cancer Chemotherapy and Pharmacology, 82(4), 661-668. https://doi.org/10.1007/s00280-018-3656-y