A phase I study of neoadjuvant chemotherapy with gemcitabine plus oral S-1 for resectable pancreatic cancer

Tajima,Hidehiro; Kitagawa,Hirohisa; Tsukada,Tomoya; Nakanuma,Shinich; Okamoto,Koichi; Sakai,Seisho; Makino,Isamu; Furukawa,Hiroyuki; Nakamura,Keishi; Hayashi,Hironori; Oyama,Katsunobu; Inokuchi,Masafumi; Nakagawara,Hisatoshi; Miyashita,Tomoharu; Fujita,Hideto; Itoh,Hiroshi; Takamura,Hiroyuki; Ninomiya,Itasu; Fushida,Sachio; Fujimura,Takashi; Ohta,Tetsuo

doi:10.3892/mco.2013.133

A phase I study of neoadjuvant chemotherapy with gemcitabine plus oral S-1 for resectable pancreatic cancer

Authors:
- Hidehiro Tajima
- Hirohisa Kitagawa
- Tomoya Tsukada
- Shinich Nakanuma
- Koichi Okamoto
- Seisho Sakai
- Isamu Makino
- Hiroyuki Furukawa
- Keishi Nakamura
- Hironori Hayashi
- Katsunobu Oyama
- Masafumi Inokuchi
- Hisatoshi Nakagawara
- Tomoharu Miyashita
- Hideto Fujita
- Hiroshi Itoh
- Hiroyuki Takamura
- Itasu Ninomiya
- Sachio Fushida
- Takashi Fujimura
- Tetsuo Ohta
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Affiliations: Department of Gastroenterologic Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Ishikawa 920-8641, Japan
Published online on: May 27, 2013 https://doi.org/10.3892/mco.2013.133
Pages: 768-772

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Abstract

The aim of this study was to determine the maximum‑tolerated dose (MTD), the dose-limiting toxicity (DLT) and the recommended dose (RD) of neoadjuvant chemotherapy (NAC) with gemcitabine (GEM) plus oral S-1 in patients with resectable pancreatic cancer. Thirteen patients with radiologically proven resectable pancreatic cancer were included in this study. S-1 was administered orally for 14 consecutive days, and GEM was administered on days 8 and 15 for two pre‑operative cycles. The dose of S-1 in this study was planned with fixed doses of GEM (1,000 mg/m2): 20, 30 and 40 mg/day for levels 0, 1 and 2, respectively. Treatment was initiated at level 1 in 3 patients, while adverse events occurred in 2 patients during the second course, leading to a dose reduction to level 0 for the 8 remaining patients. Two of the 10 patients enrolled at level 0 were excluded. Of the remaining 8 patients, GEM administration was terminated due to DLT on day 15, during the first course in 3 patients, while level 0 dosage reached MTD. Surgery was performed for the remaining 11 patients included in the study. Post‑operative complications included pancreatic fistulas in 5 patients and Pseudomonas aeruginosa sepsis in 1 patient. Two of the 11 patients exhibited a partial response and 9 patients stable disease. Eight of the 11 tumor specimens showed histopathological evidence of tumor cell injury. In conclusion, NAC with GEM and S-1 was not well‑tolerated in this study. However, pre‑operative chemotherapy may be effective against pancreatic cancer. Therefore, it is necessary to reconsider NAC regimens for pancreatic cancer.

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