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Panitumumab in combination with irinotecan plus S-1 (IRIS) as second-line therapy for metastatic colorectal cancer

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Abstract

Background

Irinotecan plus S-1 (IRIS) is the only oral fluoropyrimidine-based regimen reported to be non-inferior to FOLFIRI and widely used in clinical practice for metastatic colorectal cancer (mCRC) patients. However, the combination of IRIS plus an anti-EGFR agent has not been evaluated previously. This study aimed to investigate the feasibility and efficacy of IRIS with panitumumab as second-line therapy for wild-type KRAS mCRC.

Methods

Main inclusion criteria were patients with wild-type KRAS mCRC refractory to one prior chemotherapy regimen for mCRC, ECOG PS 0–2, and age ≥20 years. Patients received panitumumab (6 mg/kg) and irinotecan (100 mg/m2) on days 1 and 15 and S-1 (40–60 mg according to body surface area) twice daily for 2 weeks, repeated every 4 weeks. The primary endpoint was the feasibility of the therapy. The secondary endpoints were response rate (RR), progression-free survival (PFS), and overall survival (OS).

Results

A total of 36 patients received protocol treatment in eight centers. Of these, 23 patients (63.9 %) completed protocol treatment, demonstrating achievement of the primary endpoint. The most frequent grade 3/4 toxicities were diarrhea (16.7 %), acne-like rash (13.9 %), and neutropenia (11.1 %). The overall RR was 33.3 % (12/36). Of these patients, five underwent conversion surgery. Median PFS and OS were 9.5 months (95 % CI 3.5–15.4 months) and 20.1 months (95 % CI 16.7–23.2 months), respectively.

Conclusion

IRIS plus panitumumab has an acceptable toxicity profile and a promising efficacy in patients with previously treated wild-type KRAS mCRC. Accordingly, this regimen can be an additional treatment option for second-line chemotherapy in wild-type KRAS mCRC.

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References

  1. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55(2):74–108

    Article  PubMed  Google Scholar 

  2. Van Cutsem E, Cervantes A, Nordlinger B, Arnold D, Group EGW (2014) Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 25(Suppl 3):iii1–iii9. doi:10.1093/annonc/mdu260

    Article  PubMed  Google Scholar 

  3. Tournigand C, André T, Achille E, Lledo G, Flesh M, Mery-Mignard D, Quinaux E, Couteau C, Buyse M, Ganem G, Landi B, Colin P, Louvet C, de Gramont A (2004) FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 22(2):229–237. doi:10.1200/JCO.2004.05.113

    Article  CAS  PubMed  Google Scholar 

  4. Di Fiore F, Blanchard F, Charbonnier F, Le Pessot F, Lamy A, Galais MP, Bastit L, Killian A, Sesboüé R, Tuech JJ, Queuniet AM, Paillot B, Sabourin JC, Michot F, Michel P, Frebourg T (2007) Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy. Br J Cancer 96(8):1166–1169. doi:10.1038/sj.bjc.6603685

    Article  PubMed  PubMed Central  Google Scholar 

  5. Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD (2008) Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26(10):1626–1634. doi:10.1200/JCO.2007.14.7116

    Article  CAS  PubMed  Google Scholar 

  6. De Roock W, Piessevaux H, De Schutter J, Janssens M, De Hertogh G, Personeni N, Biesmans B, Van Laethem JL, Peeters M, Humblet Y, Van Cutsem E, Tejpar S (2008) KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol 19(3):508–515. doi:10.1093/annonc/mdm496

    Article  PubMed  Google Scholar 

  7. Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, André T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tzekova V, Collins S, Oliner KS, Rong A, Gansert J (2010) Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol 28(31):4706–4713. doi:10.1200/JCO.2009.27.6055

    Article  CAS  PubMed  Google Scholar 

  8. Muro K, Boku N, Shimada Y, Tsuji A, Sameshima S, Baba H, Satoh T, Denda T, Ina K, Nishina T, Yamaguchi K, Takiuchi H, Esaki T, Tokunaga S, Kuwano H, Komatsu Y, Watanabe M, Hyodo I, Morita S, Sugihara K (2010) 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 11(9):853–860. doi:10.1016/S1470-2045(10)70181-9

    Article  CAS  PubMed  Google Scholar 

  9. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247. doi:10.1016/j.ejca.2008.10.026

    Article  CAS  PubMed  Google Scholar 

  10. Komatsu Y, Yuki S, Sogabe S, Fukushima H, Nakatsumi H, Kobayashi Y, Iwanaga I, Nakamura M, Hatanaka K, Miyagishima T, Kudo M, Munakata M, Meguro T, Tateyama M, Sakata Y (2012) Phase II study of combined chemotherapy with irinotecan and S-1 (IRIS) plus bevacizumab in patients with inoperable recurrent or advanced colorectal cancer. Acta Oncol 51(7):867–872. doi:10.3109/0284186X.2012.682629

    Article  CAS  PubMed  Google Scholar 

  11. Komatsu Y, Ishioka C, Shimada K, Yamada Y, Gamoh M, Sato A, Yamaguchi T, Yuki S, Morita S, Takahashi S, Goto R, Kurihara M (2015) Study protocol of the TRICOLORE trial: a randomized phase III study of oxaliplatin-based chemotherapy versus combination chemotherapy with S-1, irinotecan, and bevacizumab as first-line therapy for metastatic colorectal cancer. BMC Cancer 15:626. doi:10.1186/s12885-015-1630-1

    Article  PubMed  PubMed Central  Google Scholar 

  12. Cohn AL, Shumaker GC, Khandelwal P, Smith DA, Neubauer MA, Mehta N, Richards D, Watkins DL, Zhang K, Yassine MR (2011) An open-label, single-arm, phase 2 trial of panitumumab plus FOLFIRI as second-line therapy in patients with metastatic colorectal cancer. Clin Colorectal Cancer 10(3):171–177. doi:10.1016/j.clcc.2011.03.022

    Article  CAS  PubMed  Google Scholar 

  13. Rothenberg ML, Cox JV, Butts C, Navarro M, Bang YJ, Goel R, Gollins S, Siu LL, Laguerre S, Cunningham D (2008) Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX-4) as second-line therapy in metastatic colorectal cancer: a randomized phase III noninferiority study. Ann Oncol 19(10):1720–1726. doi:10.1093/annonc/mdn370

    Article  CAS  PubMed  Google Scholar 

  14. Köhne CH, De Greve J, Hartmann JT, Lang I, Vergauwe P, Becker K, Braumann D, Joosens E, Müller L, Janssens J, Bokemeyer C, Reimer P, Link H, Späth-Schwalbe E, Wilke HJ, Bleiberg H, Den Van, Brande J, Debois M, Bethe U, Van Cutsem E (2008) Irinotecan combined with infusional 5-fluorouracil/folinic acid or capecitabine plus celecoxib or placebo in the first-line treatment of patients with metastatic colorectal cancer. EORTC study 40015. Ann Oncol 19(5):920–926. doi:10.1093/annonc/mdm544

    Article  PubMed  Google Scholar 

  15. Cassidy J, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Saltz L (2008) Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol 26(12):2006–2012. doi:10.1200/JCO.2007.14.9898

    Article  CAS  PubMed  Google Scholar 

  16. Yamada Y, Takahari D, Matsumoto H, Baba H, Nakamura M, Yoshida K, Yoshida M, Iwamoto S, Shimada K, Komatsu Y, Sasaki Y, Satoh T, Takahashi K, Mishima H, Muro K, Watanabe M, Sakata Y, Morita S, Shimada Y, Sugihara K (2013) Leucovorin, fluorouracil, and oxaliplatin plus bevacizumab versus S-1 and oxaliplatin plus bevacizumab in patients with metastatic colorectal cancer (SOFT): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol 14(13):1278–1286. doi:10.1016/S1470-2045(13)70490-X

    Article  CAS  PubMed  Google Scholar 

  17. Arkenau HT, Arnold D, Cassidy J, Diaz-Rubio E, Douillard JY, Hochster H, Martoni A, Grothey A, Hinke A, Schmiegel W, Schmoll HJ, Porschen R (2008) Efficacy of oxaliplatin plus capecitabine or infusional fluorouracil/leucovorin in patients with metastatic colorectal cancer: a pooled analysis of randomized trials. J Clin Oncol 26(36):5910–5917. doi:10.1200/JCO.2008.16.7759

    Article  CAS  PubMed  Google Scholar 

  18. Fuchs CS, Marshall J, Mitchell E, Wierzbicki R, Ganju V, Jeffery M, Schulz J, Richards D, Soufi-Mahjoubi R, Wang B, Barrueco J (2007) Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol 25(30):4779–4786. doi:10.1200/JCO.2007.11.3357

    Article  CAS  PubMed  Google Scholar 

  19. Maughan TS, Adams RA, Smith CG, Meade AM, Seymour MT, Wilson RH, Idziaszczyk S, Harris R, Fisher D, Kenny SL, Kay E, Mitchell JK, Madi A, Jasani B, James MD, Bridgewater J, Kennedy MJ, Claes B, Lambrechts D, Kaplan R, Cheadle JP, Investigators MCT (2011) Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet 377(9783):2103–2114. doi:10.1016/S0140-6736(11)60613-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ajani JA, Faust J, Ikeda K, Yao JC, Anbe H, Carr KL, Houghton M, Urrea P (2005) Phase I pharmacokinetic study of S-1 plus cisplatin in patients with advanced gastric carcinoma. J Clin Oncol 23(28):6957–6965. doi:10.1200/JCO.2005.01.917

    Article  CAS  PubMed  Google Scholar 

  21. Ajani JA, Lee FC, Singh DA, Haller DG, Lenz HJ, Benson AB, Yanagihara R, Phan AT, Yao JC, Strumberg D (2006) Multicenter phase II trial of S-1 plus cisplatin in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol 24(4):663–667. doi:10.1200/JCO.2005.04.2994

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank all patients, clinicians, and support stuff who participated in this study. We also thank Dr. Hiroaki Mikasa, Kimiko Fukuchi, and Michiko Yoshimaru for their advice and kind help. This study was partly supported by the research fund from Taiho Pharmaceutical Co. Ltd. The sponsor played no role in the design or conduct of the study; in the collection, management, analyses, or interpretation of data; or in the preparation, review, or approval of the manuscript.

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Authors and Affiliations

  1. Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan

    Toshi Takaoka, Tetsuo Kimura, Hiroshi Miyamoto, Takahiro Goji, Shinji Kitamura, Hiromi Yano, Koichi Okamoto, Masako Kimura, Toshiya Okahisa, Naoki Muguruma & Tetsuji Takayama

  2. Department of Surgery, Shonan Kamakura General Hospital, 1370-1, Okamoto, Kamakura, Kanagawa, 247-8533, Japan

    Rai Shimoyama

  3. Department of Surgery, Fukuoka Tokushukai Medical Center, 4-5, Sugukita, Kasuga, Fukuoka, 816-0864, Japan

    Shunji Kawamoto

  4. Department of Surgery, Kishiwada Tokushukai Hospital, 4-27-1, Kamori-cho, Kishiwada, Osaka, 596-8522, Japan

    Kazuki Sakamoto

  5. Department of Integrated Medicine, Kagawa University Hospital, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan

    Fuminori Goda

  6. Kochi Health Sciences Center, 2125-1 Ike, Kochi, 781-8555, Japan

    Yuji Negoro

  7. Kobe City Medical Center General Hospital, 2-2-1, Minatojima, Minamimachi, Chuo-ku, Kobe, 650-0047, Japan

    Akihito Tsuji

  8. Gastroenterology Center, Sapporo Higashi Tokushukai Hospital, 14-3-1, Higashi, Kita 33-jo, Higashi-ku, Sapporo, 065-0033, Japan

    Koji Yoshizaki

  9. Department of Molecular Target Exploration, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-ku, Sapporo, 060-8556, Japan

    Yoshiro Niitsu

Authors
  1. Toshi Takaoka
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  2. Tetsuo Kimura
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  14. Koichi Okamoto
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  16. Toshiya Okahisa
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  17. Naoki Muguruma
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  18. Yoshiro Niitsu
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  19. Tetsuji Takayama
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Corresponding author

Correspondence to Tetsuji Takayama.

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Conflict of interest

Tetsuji Takayama has received research funding from Taiho Pharmaceutical Co. Ltd. All other authors declare that they have no conflict of interest relevant to this study.

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Takaoka, T., Kimura, T., Shimoyama, R. et al. Panitumumab in combination with irinotecan plus S-1 (IRIS) as second-line therapy for metastatic colorectal cancer. Cancer Chemother Pharmacol 78, 397–403 (2016). https://doi.org/10.1007/s00280-016-3096-5

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