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

• Published in: Cancer chemotherapy and pharmacology Vol. 82; no. 4; pp. 661 - 668
• Main Authors: Shibuya, Hitoshi, Hijioka, Susumu, Sakamoto, Yasunari, Ito, Tetsuhide, Ueda, Keijiro, Komoto, Izumi, Kobayashi, Noritoshi, Kudo, Atsushi, 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
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-10-2018; Springer Nature B.V
• Subjects: 5-Fluorouracil; Cancer Research; Chemotherapy; Hematology; Liver; Medicine; Medicine & Public Health; Nausea; Neuroendocrine tumors; Oncology; Original Article; Pancreas; Pancreatic cancer; Pharmacology/Toxicology; Streptozocin; Toxicity; Tumors; Japan; Prognostic factor; Ki67 proliferation index; Streptozocin; Monotherapy; Pancreatic neuroendocrine tumor
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-018-3656-y

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.