A phase I study of preoperative (neoadjuvant) chemotherapy with gemcitabine plus nab-paclitaxel for resectable pancreatic cancer

Hidehiro Tajima; Isamu Makino; Ryosuke Gabata; Mitsuyoshi Okazaki; Yoshinao Ohbatake; Hiroyuki Shimbashi; Shinich Nakanuma; Hiroto Saitoh; Mari Shimada; Takahisa Yamaguchi; Koichi Okamoto; Hideki Moriyama; Jun Kinoshita; Keishi Nakamura; Tomoharu Miyashita; Itasu Ninomiya; Sachio Fushida; Hiroko Ikeda; Tetsuo Ohta

doi:10.3892/mco.2020.2188

A phase I study of preoperative (neoadjuvant) chemotherapy with gemcitabine plus nab-paclitaxel for resectable pancreatic cancer

Mol Clin Oncol. 2021 Feb;14(2):26. doi: 10.3892/mco.2020.2188. Epub 2020 Dec 14.

Authors

Hidehiro Tajima¹, Isamu Makino¹, Ryosuke Gabata¹, Mitsuyoshi Okazaki¹, Yoshinao Ohbatake¹, Hiroyuki Shimbashi¹, Shinich Nakanuma¹, Hiroto Saitoh², Mari Shimada², Takahisa Yamaguchi², Koichi Okamoto², Hideki Moriyama², Jun Kinoshita², Keishi Nakamura², Tomoharu Miyashita¹, Itasu Ninomiya², Sachio Fushida², Hiroko Ikeda³, Tetsuo Ohta¹

Affiliations

¹ Department of Hepato-Biliary-Pancreatic Surgery, Division of Cancer Medicine, Graduate School of Medicine Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
² Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medicine Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
³ Division of Pathology, Kanazawa University Hospital, Kanazawa, Ishikawa 920-8641, Japan.

Abstract

Neoadjuvant chemotherapy (NAC) has become a standard treatment for borderline resectable pancreatic ductal adenocarcinoma (PDAC). The present study examined the maximum tolerated dose of NAC with gemcitabine plus nab-paclitaxel (GnP) in patients with resectable PDAC. Between 2015 and 2019, 39 patients with resectable PDAC were enrolled in the present study. GnP was administered for two 28-day cycles on days 1, 8 and 15. The planned doses for levels 1, 2 and 3 were 75, 100 and 125 mg/m², respectively, for nab-paclitaxel and 600, 800 and 1,000 mg/m², respectively, for gemcitabine. Dose-limiting toxicity (neutropenia, anemia, thrombocytopenia and/or liver injury) was observed in 44.4% of patients treated at dose level 1 (21 patients) and 60.0% of those treated at dose level 2 (18 patients). Therefore, the maximum tolerated dose was set as level 1. Six patients withdrew from protocol treatment because of non-hematologic adverse events (skin rash, pancreatitis and biliary tract infection). Among the 31 patients with pathologically confirmed PDAC, partial response, stable disease and disease progression were recorded in 4 (12.9%), 24 (77.4%) and 3 (9.7%) patients, respectively. NAC significantly reduced tumor size according to computed tomography, and CA19-9 levels and the ¹⁸F-fluorodeoxyglucose maximum standardized uptake value were decreased in positron emission tomography. No postoperative complications attributable to NAC were recognized. Among the 27 patients with PDAC who underwent resection, the pathological treatment effect was judged as grades Ia, Ib and II in 21 (77.8%), 4 (14.8%) and 2 (7.4%) patients, respectively. R0 resection was performed in 24 out of 27 patients (88.9%). Adjuvant chemotherapy with oral S-1 was administered to 21 out of 27 patients (77.8%). In conclusion, NAC with GnP was safe and feasible for resectable PDAC at dose level 1. In the future, verification of the long-term results of the present study will be necessary, and a phase II clinical trial is anticipated.

Keywords: NAC; gemcitabine; nab-paclitaxel; pancreatic cancer; phase I.