Efficacy and safety of neoadjuvant nab‐paclitaxel plus gemcitabine therapy in patients with borderline resectable pancreatic cancer: A multicenter single‐arm phase II study (NAC‐GA trial)

• Published in: Annals of gastroenterological surgery 2023-11, Vol.7 (6), p.997-1008
• Main Authors: Okada, Ken‐ichi, Kimura, Kenjiro, Yamashita, Yo‐Ichi, Shibuya, Kazuto, Matsumoto, Ippei, Satoi, Sohei, Yoshida, Kazuhiro, Kodera, Yasuhiro, Akahori, Takahiro, Hirono, Seiko, Eguchi, Hidetoshi, Asakuma, Mitsuhiro, Tani, Masaji, Hatano, Etsuro, Ikoma, Hisashi, Ohira, Go, Hayashi, Hiromitsu, Wan, Ke, Shimokawa, Toshio, Kawai, Manabu, Yamaue, Hiroki
• Format: Article
• Language: English
• Subjects: Antigens; borderline resectable; Cancer therapies; Chemotherapy; Clinical trials; Diarrhea; gemcitabine; Laparoscopy; Metastasis; nab‐paclitaxel; Neurotoxicity; Neutropenia; Original; Pancreatic cancer; Patients; phase II clinical trial; Quality of life; Questionnaires; Registration; Surgery
• ISSN: 2475-0328; 2475-0328
• DOI: 10.1002/ags3.12712

Background Nab‐paclitaxel plus gemcitabine is a standard treatment for metastatic/locally advanced pancreatic cancer. The effectiveness of neoadjuvant therapy with nab‐paclitaxel plus gemcitabine (GnP‐NAT) in patients with borderline resectable pancreatic cancer (BRPC) remains unclear. Patients and Methods This single‐arm phase II trial included 61 patients with BRPC that were treated with two cycles of GnP‐NAT, (nab‐paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2), on days 1, 8, and 15 over a 4‐week period, which comprised one cycle. The primary endpoint was overall survival time. In the absence of disease progression, patients underwent planned pancreatectomy. Results Median overall survival, the primary endpoint, was 25.2 months, and the median recurrence‐free survival was 12.3 months. The overall rate of grade 3/4 events was 73.8%. One patient, who had a history of radiation therapy for past esophageal cancer, died from exacerbation via pneumonia. The overall resection rate was 73.8% (n = 45), and the R0 resection rate was 63.9% (n = 39). Overall, postoperative complications were found in 19 patients (42%) with 24 events, and nine patients (20%) with nine events ≥ grade IIIa, based on Dindo's classification. Conclusions This protocol treatment is thought to be a feasible, safe, and promising treatment regimen, but we caution against its use in patients with a history of interstitial lung disease and/or prior pulmonary irradiation. The survival data from this study suggest the need for further investigations of GnP‐NAT efficacy in patients with BRPC, as well as prospective evaluation of adverse events. Clinical Trial Registration UMIN Clinical Trials Registry, UMIN000024154 and ClinicalTrials.gov, NCT02926183. Neoadjuvant nab‐paclitaxel/gemcitabine brings median 25 months overall survival in borderline resectable pancreatic cancer. The study cautions against neoadjuvant nab‐paclitaxel/gemcitabine therapy in patients with pulmonary risk. The prognosis in the borderline resectable‐arterial group was worse than that of patients in venous group.