Skip to main content
SpringerLink
Log in

Salvage Chemotherapy by FOLFIRI Regimen for Poorly Differentiated Gastrointestinal Neuroendocrine Carcinoma

  • Original Research
  • Published:
Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

Abstract

Purpose

Chemotherapy is the mainstay treatment for advanced poorly differentiated gastrointestinal neuroendocrine carcinoma (GI-NEC), with platinum-containing regimens being the optimal first-line regimen. However, the role and efficacy of second-line chemotherapy for GI-NEC are unclear. This study aimed to evaluate the feasibility and efficacy of fluorouracil, leucovorin, and irinotecan (FOLFIRI) as second-line therapy in patients with relapsed or recurrent GI-NEC after first-line platinum plus etoposide therapy.

Methods

We retrospectively evaluated eight consecutive patients with unresectable GI-NEC treated between 2017 and 2020. The inclusion criteria were pre-treatment with platinum doublet therapy, performance status (PS) 0–2, having measurable lesions, and treatment with FOLFIRI as second-line therapy. The overall response rate, progression-free survival (PFS), overall survival (OS), safety, and relative dose intensity were evaluated.

Results

Five patients met the inclusion criteria. Overall, 37 cycles of FOLFIRI were administered. The relative dose intensities for irinotecan, continuous infusion of 5-FU, and a bolus injection of 5-FU were 76%, 72%, and 54%, respectively. Overall, 2 of the 5 patients achieved partial response (40%), and the duration of response (DOR) was 4.0 months. The PFS and OS rates were 5.8 (95% CI, 1.5-NA) and 11 (95% CI, 6.3-NA) months, respectively. Overall, 4 of the 5 patients (80%) proceeded with further chemotherapy. Grade ≥ 3 adverse events except hematological toxicity included febrile neutropenia (n = 2), anorexia (n = 2), and fatigue (n = 1). Treatment discontinuation due to treatment-related adverse events was not observed.

Conclusions

FOLFIRI showed modest efficacy and feasibility for GI-NEC patients and has thus potential for patients who fail the first-line treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ahlman H, Nilsson O, McNicol AM, Ruszniewski P, Niederle B, Ricke J, et al. Poorly-differentiated endocrine carcinomas of midgut and hindgut origin. Neuroendocrinology. 2008;87:40–6. https://doi.org/10.1159/000109976.

    Article  CAS  PubMed  Google Scholar 

  2. Fazio N, Spada F, Giovannini M. Chemotherapy in gastroenteropancreatic (GEP) neuroendocrine carcinomas (NEC): a critical view. Cancer Treat Rev. 2013;39:270–4. https://doi.org/10.1016/j.ctrv.2012.06.009.

    Article  CAS  PubMed  Google Scholar 

  3. Mitry E, Baudin E, Ducreux M, Sabourin JC, Rufié P, Aparicio T, et al. Treatment of poorly differentiated neuroendocrine tumours with etoposide and cisplatin. Br J Cancer. 1999;81:1351–5. https://doi.org/10.1038/sj.bjc.6690325.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Iwasa S, Morizane C, Okusaka T, Ueno H, Ikeda M, Kondo S, et al. Cisplatin and etoposide as first-line chemotherapy for poorly differentiated neuroendocrine carcinoma of the hepatobiliary tract and pancreas. Jpn J Clin Oncol. 2010;40:313–8. https://doi.org/10.1093/jjco/hyp173.

    Article  PubMed  Google Scholar 

  5. von Pawel J, Jotte R, Spigel DR, O'Brien MER, Socinski MA, Mezger J, et al. Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. J Clin Oncol. 2014;32:4012–9. https://doi.org/10.1200/jco.2013.54.5392.

    Article  Google Scholar 

  6. Inoue A, Sugawara S, Yamazaki K, Maemondo M, Suzuki T, Gomi K, et al. Randomized phase II trial comparing amrubicin with topotecan in patients with previously treated small-cell lung cancer: North Japan Lung Cancer Study Group Trial 0402. J Clin Oncol. 2008;26:5401–6. https://doi.org/10.1200/jco.2008.18.1974.

    Article  CAS  PubMed  Google Scholar 

  7. Postmus PE, Berendsen HH, van Zandwijk N, Splinter TAW, Burghouts JTM, Bakker W. Retreatment with the induction regimen in small cell lung cancer relapsing after an initial response to short term chemotherapy. Eur J Cancer Clin Oncol. 1987;23:1409–11. https://doi.org/10.1016/0277-5379(87)90128-3.

    Article  CAS  PubMed  Google Scholar 

  8. Kitagawa Y, Osumi H, Shinozaki E, Ota Y, Nakayama I, Suzuki T, et al. Safety and efficacy of amrubicin monotherapy in patients with platinum-refractory metastatic neuroendocrine carcinoma of the gastrointestinal tract: a single cancer center retrospective study. Cancer Manag Res. 2019;11:5757–64. https://doi.org/10.2147/cmar.s201048.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Araki T, Takashima A, Hamaguchi T, Honma Y, Iwasa S, Okita N, et al. Amrubicin in patients with platinum-refractory metastatic neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma of the gastrointestinal tract. Anti-Cancer Drugs. 2016;27:794–9. https://doi.org/10.1097/cad.0000000000000393.

    Article  CAS  PubMed  Google Scholar 

  10. Nio K, Arita S, Isobe T, Kusaba H, Kohashi K, Kajitani T, et al. Amrubicin monotherapy for patients with extrapulmonary neuroendocrine carcinoma after platinum-based chemotherapy. Cancer Chemother Pharmacol. 2015;75:829–35. https://doi.org/10.1007/s00280-015-2706-y.

    Article  CAS  PubMed  Google Scholar 

  11. Asayama M, Fuse N, Yoshino T, Yano T, Tahara M, Doi T, et al. Amrubicin for the treatment of neuroendocrine carcinoma of the gastrointestinal tract: a retrospective analysis of five cases. Cancer Chemother Pharmacol. 2011;68:1325–30. https://doi.org/10.1007/s00280-011-1619-7.

    Article  CAS  PubMed  Google Scholar 

  12. Ando T, Hosokawa A, Yoshita H, Ueda A, Kajiura S, Mihara H, et al. Amrubicin monotherapy for patients with platinum-refractory gastroenteropancreatic neuroendocrine carcinoma. Gastroenterol Res Pract. 2015;2015:425876–5. https://doi.org/10.1155/2015/425876.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hentic O, Hammel P, Couvelard A, Rebours V, Zappa M, Palazzo M, et al. FOLFIRI regimen: an effective second-line chemotherapy after failure of etoposide-platinum combination in patients with neuroendocrine carcinomas grade 3. Endocr Relat Cancer. 2012;19:751–7. https://doi.org/10.1530/erc-12-0002.

    Article  CAS  PubMed  Google Scholar 

  14. Nagtegaal ID, Odze RD, Klimstra D, Paradis V, Rugge M, Schirmacher P, et al. The 2019 WHO classification of tumours of the digestive system. Histopathology. 2020;76:182–8. https://doi.org/10.1111/his.13975.

    Article  PubMed  Google Scholar 

  15. Muro K, Boku N, Shimada Y, Tsuji A, Sameshima S, Baba H, et al. Irinotecan plus S-1 (IRIS) versus fluorouracil and folinic acid plus irinotecan (FOLFIRI) as second-line chemotherapy for metastatic colorectal cancer: a randomised phase 2/3 non-inferiority study (FIRIS study). Lancet Oncol. 2010;11:853–60. https://doi.org/10.1016/s1470-2045(10)70181-9.

    Article  CAS  PubMed  Google Scholar 

  16. Fuse N, Doi T, Ohtsu A, Yano T, Hamamoto Y, Minashi K, et al. Safety of irinotecan and infusional fluorouracil/leucovorin (FOLFIRI) in Japan: a retrospective review of 48 patients with metastatic colorectal cancer. Int J Clin Oncol. 2008;13:144–9. https://doi.org/10.1007/s10147-007-0737-z.

    Article  CAS  PubMed  Google Scholar 

  17. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47. https://doi.org/10.1016/j.ejca.2008.10.026.

    Article  CAS  Google Scholar 

  18. Kanda Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant. 2013;48:452–8. https://doi.org/10.1038/bmt.2012.244.

    Article  CAS  PubMed  Google Scholar 

  19. Horita N, Yamamoto M, Sato T, Tsukahara T, Nagakura H, Tashiro K, et al. Amrubicin for relapsed small-cell lung cancer: a systematic review and meta-analysis of 803 patients. Sci Rep. 2016;6:18999. https://doi.org/10.1038/srep18999.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sato I, Ueda N, Kinoshita E, et al. Curatively resected case of non-functioning pancreatic neuroendocrine carcinoma with multiple liver metastases after downstaging with S-1 monotherapy. Gan To Kagaku Ryoho. 2010;37:1341–4.

    PubMed  Google Scholar 

  21. Wang L, Song Q, Li J, Chen X. S-1 treatment leading to complete remission of advanced duodenal adenocarcinoma: a case report. Mol Clin Oncol. 2015;3:1184–6. https://doi.org/10.3892/mco.2015.607.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hirai F, Seto T, Inamasu E, Toyokawa G, Yoshida T, Nosaki K, et al. Results of S-1-based chemotherapy for platinum (and antrathycline)-refractory advanced thymic carcinoma. Anticancer Res. 2014;34:5743–7.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Editage (www.editage.jp) for English language editing.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, National Hospital Organization Nagoya Medical Center, 4-1-1 Sannomaru, Naka-ku, Nagoya, Aichi, 460-0001, Japan

    Keiji Sugiyama, Kazuhiro Shiraishi, Mariko Sato, Riko Nishibori & Chiyoe Kitagawa

  2. Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan

    Kazuki Nozawa

Authors
  1. Keiji Sugiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kazuhiro Shiraishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mariko Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Riko Nishibori
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kazuki Nozawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chiyoe Kitagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Keiji Sugiyama.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

The study was approved by the Institutional Review Board (No. 2020-002).

Informed Consent

The need for informed consent was waived owing to the retrospective nature of the study. An opt-out option was provided instead.

Consent for Publication

Not applicable.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sugiyama, K., Shiraishi, K., Sato, M. et al. Salvage Chemotherapy by FOLFIRI Regimen for Poorly Differentiated Gastrointestinal Neuroendocrine Carcinoma. J Gastrointest Canc 52, 947–951 (2021). https://doi.org/10.1007/s12029-020-00516-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12029-020-00516-7

Keywords

Search

Navigation