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A triplet combination with capecitabine/oxaliplatin/irinotecan (XELOXIRI) plus cetuximab as first-line therapy for patients with metastatic colorectal cancer: a dose escalation study

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Abstract

Purpose

The addition of cetuximab to triplet chemotherapy can increase treatment efficacy for patients with metastatic colorectal cancer (mCRC). We explored the dose-limiting toxicity and feasibility of a triweekly capecitabine, oxaliplatin, irinotecan, plus cetuximab (XELOXIRI plus cetuximab) regimen in patients with wild-type KRAS mCRC.

Methods

Patients received oxaliplatin (100 mg/m2, day 1), capecitabine (1700 mg/m2 per day from day 2 to 15), irinotecan (100, 120, and 150 mg/m2 for dose levels 1, 2, 3, respectively, on day 1), and cetuximab (400 mg/m2, day 1 and, thereafter, 250 mg/m2 every week), repeated every 3 weeks. Dose-limiting toxicities (DLTs) were assessed in the first 2 treatment cycles to determine the maximum tolerated dose (MTD) and the recommended dose (RD).

Results

Twelve patients received a median of 7 cycles of therapy (range 2–10). The DLT was grade 4 neutropenia, observed in 1 of 6 patients at dose level 2. The MTD was not reached at dose level 3. Therefore, the RD of irinotecan was defined as 150 mg/m2. Most common grade ≥ 3 toxicities were neutropenia (50%), diarrhea (17%), and febrile neutropenia (8%). The response rate was 83% (complete and partial response: 1 and 9 patient(s), respectively), including 4 conversion cases.

Conclusions

The combination of XELOXIRI and cetuximab is feasible and has an acceptable toxicity profile; neutropenia was the DLT. The RD of irinotecan is 150 mg/m2. The observed response rate was promising and warrants further investigation.

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Authors and Affiliations

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

    Yasushi Sato

  2. Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo, Japan

    Masahiro Hirakawa, Hiroyuki Ohnuma & Junji Kato

  3. Division of Gastroenterology, Sapporo Kyoritsu Gorinbashi Hospital, Sapporo, Japan

    Minoru Takahashi

  4. Division of Gastroenterology, Kiyota Hospital, Sapporo, Japan

    Tetsuro Okamoto

  5. Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan

    Koichi Okamoto, Hiroshi Miyamoto, Naoki Muguruma & Tetsuji Takayama

  6. Department of Gastroenterological Surgery, St. Marianna Medical University Toyoko Hospital, Yokohama, Japan

    Tomohisa Furuhata

  7. Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan

    Ichiro Takemasa

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  1. Yasushi Sato
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  2. Masahiro Hirakawa
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Correspondence to Yasushi Sato.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Sato, Y., Hirakawa, M., Ohnuma, H. et al. A triplet combination with capecitabine/oxaliplatin/irinotecan (XELOXIRI) plus cetuximab as first-line therapy for patients with metastatic colorectal cancer: a dose escalation study. Cancer Chemother Pharmacol 80, 1133–1139 (2017). https://doi.org/10.1007/s00280-017-3458-7

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