A randomised phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel for locally advanced pancreatic cancer (JCOG1407).

Masato Ozaka, Kohei Nakachi, Satoshi Kobayashi, Akihiro Ohba, Hiroshi Imaoka, Takeshi Terashima, Hiroshi Ishii, Junki Mizusawa, Hiroshi Katayama, Tomoko Kataoka, Takuji Okusaka, Masafumi Ikeda, Naoki Sasahira, Haruo Miwa, Eishiro Mizukoshi, Naohiro Okano, Nobumasa Mizuno, Tomohisa Yamamoto, Yoshito Komatsu, Akiko Todaka, Ken Kamata, Masayuki Furukawa, Nao Fujimori, Akio Katanuma, Yukiko Takayama, Hidetaka Tsumura, Haruhiko Fukuda, Makoto Ueno, Junji Furuse

Journal: European journal of cancer (Oxford, England : 1990) 2023;181():135-144

PMID: 36652891

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Abstract

AIM

We compared the efficacy of modified 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) with that of gemcitabine plus nab-paclitaxel (GnP) for locally advanced pancreatic cancer (LAPC).

METHODS

Patients with untreated LAPC were randomly assigned (1:1) to receive mFOLFIRINOX or GnP. One-year overall survival (OS) was the primary endpoint. The major secondary end-points included progression-free survival (PFS), response rate (RR), carbohydrate antigen 19-9 (CA19-9) response, and adverse events. The sample size was 124 patients to select a more effective regimen with a minimum probability of 0.85 and to examine the null hypothesis of the 1-year OS <53%.

RESULTS

Of the 126 patients enrolled from 29 institutions, 125 were deemed eligible. The 1-year OS was 77.4% (95% CI, 64.9-86.0) and 82.5% (95% CI, 70.7-89.9) in the mFOLFIRINOX and GnP arms, respectively. The median PFS was 11.2 (95% CI, 9.9-15.9) and 9.4 months (95% CI, 7.4-12.8) in the mFOLFIRINOX and GnP arms, respectively. The RR and CA19-9 response rate were 30.9% (95% CI, 19.1-44.8) and 57.1% (95% CI, 41.0-72.3) and 42.1% (95% CI 29.1-55.9) and 85.0% (95% CI, 70.2-94.3) in the mFOLFIRINOX and GnP arms, respectively. Grade 3-4 diarrhoea and anorexia were predominant in the mFOLFIRINOX arm.

CONCLUSION

GnP was considered the candidate for a subsequent phase III trial because of its better RR, CA19-9 response, and mild gastrointestinal toxicities. Both regimens displayed higher efficacy in the 1-year survival than in the historical data of gemcitabine monotherapy.

Address: Department of Hepato-Biliary-Pancreatic Medicine, Gastroenterology Center, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan. Electronic address: [email protected].; Department of Medical Oncology, Tochigi Cancer Center, Utsunomiya, Japan.; Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan.; Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.; Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.; Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan.; Clinical Research Center, Chiba Cancer Center, Chiba, Japan.; Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan.; Department of Hepato-Biliary-Pancreatic Medicine, Gastroenterology Center, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.; Department of Gastroenterology, Yokohama City University Medical Center, Yokohama, Japan.; Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.; Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan.; Department of Surgery, Kansai Medical University Hospital, Osaka, Japan.; Department of Gastroenterology, Hokkaido University Hospital, Sapporo, Japan.; Divison of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.; Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.; Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.; Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.; Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Japan.; Department of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.; Department of Gastroenterological Oncology, Hyogo Cancer Center, Akashi, Japan.; Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan; Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.

DOI: 10.1016/j.ejca.2022.12.014

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MeSH Terms: Humans, Gemcitabine, Antineoplastic Combined Chemotherapy Protocols, Pancreatic Neoplasms, Deoxycytidine, CA-19-9 Antigen, Fluorouracil, Paclitaxel, Albumins, Leucovorin