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Clinical Studies

A phase II randomised trial of induction chemotherapy followed by concurrent chemoradiotherapy in locally advanced pancreatic cancer: the Taiwan Cooperative Oncology Group T2212 study

British Journal of Cancer volume 126, pages 1018–1026 (2022)Cite this article

Subjects

Abstract

Background

The objective of this study was to evaluate the efficacy and safety of induction chemotherapy (ICT), GOFL (gemcitabine, oxaliplatin plus fluorouracil (5-FU)/leucovorin) versus modified FOLFIRINOX (irinotecan, oxaliplatin plus 5-FU/leucovorin), followed by concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic adenocarcinoma (LAPC).

Methods

Chemo-naive patients with measurable LAPC were eligible and randomly assigned to receive biweekly ICT with either mFOLFIRINOX or GOFL for 3 months. Patients without systemic progression would have 5-FU- or gemcitabine-based CCRT (5040 cGy/28 fractions) and were then subjected to surgery or continuation of chemotherapy until treatment failure. The primary endpoint was 9-month progression-free survival (PFS) rate.

Results

Between July 2013 and January 2019, 55 patients were enrolled. After ICT, 21 (77.8%) of 27 patients who received mFOLFIRINOX and 17 (60.7%) of 28 patients who received GOFL completed CCRT. Of them, one and five had per-protocol R0/R1 resection. On intent-to-treat analysis, the 9-month PFS rate, median PFS and overall survival in mFOLFIRINOX and GOFL arms were 30.5% versus 35.9%, 6.6 (95% confidence interval: 5.9–12.5) versus 7.6 months (3.9–12.3) and 19.6 (13.4–22.9) versus 17.9 months (13.4–23.9), respectively. Grade 3–4 neutropenia and diarrhoea during induction mFOLFIRINOX and GOFL were 37.0% versus 21.4% and 14.8% versus 3.6%, respectively.

Conclusion

Induction GOFL and mFOLFIRINOX followed by CCRT provided similar clinical outcomes in LAPC patients.

Clinicaltrial.gov identifier

NCT01867892.

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Fig. 1: Schema of study flow.
Fig. 2: Kaplan–Meier curves of entire population and different treatment arms.

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Data availability

All data generated and analysed during this study are included in this article and its Supplementary information files.

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Acknowledgements

We thank all the hospitals for enrolling patients in this trial including National Cheng Kung University Hospital, Tainan (to Y-SS, N-JC); Veterans General Hospital, Taipei City (to C-PL); Mackay Memorial Hospital, Taipei (to JL); National Taiwan University Hospital, Taipei City (to S-HY); Veterans General Hospital, Kaohsiung City (to S-JL, Ming-Sun Yu), Tri-Service General Hospital, Taipei (to P-YC, J-HC), Linkou Chang Gung Memorial Hospital, Taoyuan (to J-SC) and Taipei Medical University Hospital, Taipei City (to Her-Shyong Shiah). We are grateful for the participation of all the patients and their families and to make this study possible, and also for the help of research nurses and statisticians from the Taiwan Cooperative Oncology Group. In particular, we would like to thank Ms. Shu-Chuan Lai for her tremendous efforts in the comprehensive statistical analyses of this trial. Oxaliplatin (Oxalip®) and irinotecan (Irino®) were kindly sponsored by TTY Biopharm Company Limited, Taipei, Taiwan.

Funding

This study was conducted by the Taiwan Cooperative Oncology Group with funding (number CA-101–108-PP 25) from National Health Research Institutes, Ministry of Health and Welfare, Executive Yuan, Taiwan.

Author information

Author notes

  1. These authors contributed equally: Yung-Yeh Su, Yen-Feng Chiu.

  2. These authors jointly supervised this work: Yan-Shen Shan, Hui-Ju Ch’ang, Li-Tzong Chen.

Authors and Affiliations

  1. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Yung-Yeh Su & Yan-Shen Shan

  2. National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan

    Yung-Yeh Su, Nai-Jung Chiang, Hui-Ju Ch’ang & Li-Tzong Chen

  3. Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Yung-Yeh Su, Nai-Jung Chiang & Li-Tzong Chen

  4. Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan

    Yen-Feng Chiu

  5. Division of Clinical Skills Training, Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan

    Chung-Pin Li

  6. Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

    Chung-Pin Li

  7. National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan

    Chung-Pin Li

  8. Department of Oncology, National Taiwan University Hospital and Graduate Institute of Oncology, National Taiwan University, College of Medicine, Taipei, Taiwan

    Shih-Hung Yang

  9. Department of Hematology, Mackay Memorial Hospital, Taipei, Taiwan

    Johnson Lin

  10. Department of Hematology, Veteran General Hospital, Kaohsiung, Taiwan

    Shyh-Jer Lin

  11. Division of Hematology/Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

    Ping-Ying Chang

  12. Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Yan-Shen Shan

  13. Department of Radiation Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Hui-Ju Ch’ang

  14. Taipei Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan

    Hui-Ju Ch’ang

  15. Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Li-Tzong Chen

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Contributions

H-JC, Y-SS, L-TC and Y-YS: conceptualisation, funding acquisition and writing—review & editing; Y-YS, Y-SS, C-PL, S-HY, JL, S-JL, P-YC, N-JC, L-TC and H-JC: data curation; Y-YS, H-JC, Y-FC, L-TC: formal analysis, methodology and writing—original draft; H-JC: project administration; Y-FC, Y-YS: software; Y-SS and L-TC: supervision; Y-YS, Y-SS, C-PL, S-HY, JL, S-HY, S-HL, P-YC, N-JC and L-TC: validation.

Corresponding authors

Correspondence to Yan-Shen Shan, Hui-Ju Ch’ang or Li-Tzong Chen.

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Competing interests

L-TC reports research funding from Novartis, Merck, Serono, TTY, Polaris, SyncorePharm, Pfizer, BMS; honoraria from ONO, Eli Lilly, MSD, PharmaEngine, TTY, SyncorePharm, Novartis, Astra Zeneca, Ipsen; patents and royalties from ENO-1mAb/HuniLife; membership on Board of Directors of ScinoPharm, Taiwan, Ltd. and on Scientific Advisory Committee of PharmaEngine. All the remaining authors declare no competing interests.

Ethics approval and consent to participate

The study protocol and informed consent forms were approved by the Research Ethics Committee, National Health Research Institutes, Taiwan (reference number: EC1010805) and the Institutional Review Board of each participating hospital. All subjects provided written informed consent prior to participating in the study. The study was conducted in accordance with the Declaration of Helsinki.

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Su, YY., Chiu, YF., Li, CP. et al. A phase II randomised trial of induction chemotherapy followed by concurrent chemoradiotherapy in locally advanced pancreatic cancer: the Taiwan Cooperative Oncology Group T2212 study. Br J Cancer 126, 1018–1026 (2022). https://doi.org/10.1038/s41416-021-01649-7

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