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:
Eiji Oki received lecture fee from Merck Biopharma Co., Ltd., Bayer Yakuhin Japan, Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Eli Lilly, Yakult Honsha Co., Ltd., and Takeda Pharmaceutical Co., Ltd. Akitaka Makiyama reports personal fees from Lily, personal fees from Chugai, personal fees from Takeda, outside the submitted work. Masahito Kotaka reports lecturefee from Chugai Pharmaceutical Co., Ltd., Yakult Honsha Co., Ltd., Takeda Pharmaceutical Company Limited, Merck Biopharma Co., Ltd., and Taiho Pharmaceutical Co., Ltd., outside the submitted work. Hideo Baba reports grants, personal fees and non-financial support from Taiho Pharmaceutical Co., Ltd., grants and non-financial support from Merck Biopharma Co., Ltd., during the conduct of the study; grants, personal fees and non-financial support from Ono Pharmaceutical Co., Ltd., grants, personal fees and non-financial support from Eli Lilly Japan K.K., grants and personal fees from Takeda Pharmaceutical Co., Ltd., grants and personal fees from Chugai Pharmaceutical Co., Ltd., grants from Shionogi & Co., Ltd., grants from Covidien Japan Inc., grants and non-financial support from Yakult Honsha Co.,Ltd., grants from Shin Nippon Biomedical Laboratories, Ltd., grants from Novartis-pharma K.K., grants from Toyama Chemical Co., Ltd., grants and non-financial support from Johnson & Johnson K.K., outside the submitted work. Other authors have no conflict of interest.
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
VL - 86
SP - 285
EP - 294
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
SN - 0344-5704
IS - 2
ER -
