TY - JOUR
T1 - A phase I/II study of S-1 and irinotecan (IRIS) combined with cetuximab in patients with RAS wild-type metastatic colorectal cancer (KSCC1401)
AU - Samura, Hironori
AU - Oki, Eiji
AU - Okumura, Hiroshi
AU - Yoshida, Takefumi
AU - Kai, Seiichiro
AU - Kobayashi, Kazuma
AU - Kinjo, Tatsuya
AU - Mori, Shinichiro
AU - Tohyama, Tetsuo
AU - Ohgaki, Kippei
AU - Kawanaka, Hirofumi
AU - Makiyama, Akitaka
AU - Ureshino, Norio
AU - Kotaka, Masahito
AU - Shimose, Takayuki
AU - Ando, Koji
AU - Saeki, Hiroshi
AU - Baba, Hideo
AU - Maehara, Yoshihiko
AU - Mori, Masaki
N1 - Funding Information:
We sincerely thank the participating patients and their families. We are indebted to the physicians and all other medical staff. We also thank Ms. Sakamoto and the staff at the KSCC (Kyushu Study Group of Clinical Cacner) and CReS Kyushu for their excellent data collection and management, secretarial assistance, and support. Finally, we thank James P. Mahaffey, PhD, from Edanz Group ( https://en-author-services.edanzgroup.com/ ) for editing a draft of this manuscript. This work was supported by the CReS Kyushu with funding from Merck Biopharma Co., Ltd., an affiliate of Merck KGaA, Darmstadt, Germany under a research contract.
Funding Information:
This work was supported by the CReS Kyushu with funding from Merck Serono Co., Ltd., an affiliate of Merck KGaA, Darmstadt, Germany under a research contract. Acknowledgements
Publisher Copyright:
© 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Purpose: This study was designed to assess the tolerability, efficacy, and safety of tri-weekly irinotecan plus S-1 (IRIS) and weekly cetuximab in patients with metastatic colorectal cancer (mCRC). Methods: The main eligibility criteria were RAS wild-type mCRC with no prior chemotherapy. S-1 was given orally at a dose of 40 mg/m2 (40–60 mg) twice for 2 weeks, followed by a 1-week rest. Irinotecan was given on day 1 of each cycle at a dose of 150 mg/m2. Cetuximab was administered on days 1 (400 mg/m2), 8 (250 mg/m2), and 15 (250 mg/m2), and then once weekly (250 mg/m2) thereafter. A standard 3 + 3 phase I dose de-escalation design was used to determine the maximum tolerated dose and the recommended dose (RD) of irinotecan. The primary end point of the Phase II study was overall response rate (ORR). Results: Between December 2014 and September 2017, 4 and 54 patients were enrolled in phase I and phase II studies, respectively. No dose-limiting toxicity was observed in the phase I study, and the RD of irinotecan was 150 mg/m2. In the phase II study, the ORR was 56.9% (90% confidence interval 44.4%–68.7%). The safety profile revealed that the most common grade 3/4 adverse events were neutropenia (31.4%), appetite loss (27.5%), hypokalemia (11.8%), and diarrhea (11.8%). Grade 3/4 hand–foot skin syndrome occurred in nine patients (9.8%). Conclusion: This study showed that the efficacy and safety of IRIS combined with cetuximab were comparable to those for other first-line treatments. This regimen is a good candidate for first-line treatment of RAS wild-type mCRC.
AB - Purpose: This study was designed to assess the tolerability, efficacy, and safety of tri-weekly irinotecan plus S-1 (IRIS) and weekly cetuximab in patients with metastatic colorectal cancer (mCRC). Methods: The main eligibility criteria were RAS wild-type mCRC with no prior chemotherapy. S-1 was given orally at a dose of 40 mg/m2 (40–60 mg) twice for 2 weeks, followed by a 1-week rest. Irinotecan was given on day 1 of each cycle at a dose of 150 mg/m2. Cetuximab was administered on days 1 (400 mg/m2), 8 (250 mg/m2), and 15 (250 mg/m2), and then once weekly (250 mg/m2) thereafter. A standard 3 + 3 phase I dose de-escalation design was used to determine the maximum tolerated dose and the recommended dose (RD) of irinotecan. The primary end point of the Phase II study was overall response rate (ORR). Results: Between December 2014 and September 2017, 4 and 54 patients were enrolled in phase I and phase II studies, respectively. No dose-limiting toxicity was observed in the phase I study, and the RD of irinotecan was 150 mg/m2. In the phase II study, the ORR was 56.9% (90% confidence interval 44.4%–68.7%). The safety profile revealed that the most common grade 3/4 adverse events were neutropenia (31.4%), appetite loss (27.5%), hypokalemia (11.8%), and diarrhea (11.8%). Grade 3/4 hand–foot skin syndrome occurred in nine patients (9.8%). Conclusion: This study showed that the efficacy and safety of IRIS combined with cetuximab were comparable to those for other first-line treatments. This regimen is a good candidate for first-line treatment of RAS wild-type mCRC.
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U2 - 10.1007/s00280-020-04108-x
DO - 10.1007/s00280-020-04108-x
M3 - Article
C2 - 32734398
AN - SCOPUS:85088814951
SN - 0344-5704
VL - 86
SP - 285
EP - 294
JO - Cancer chemotherapy and pharmacology
JF - Cancer chemotherapy and pharmacology
IS - 2
ER -
