Severe infusion reactions to cetuximab occur within 1 h in patients with metastatic colorectal cancer: results of a nationwide, multicenter, prospective registry study of 2126 patients in Japan.
OBJECTIVE
Infusion reactions are common adverse reactions associated with antibody preparations. However, no studies have examined the time to onset of serious infusion reactions after administering cetuximab. We aimed to investigate the timing and severity of IRs affecting Japanese patients after administration of cetuximab.


METHODS
Study subjects were identified from a nationwide prospective registry of 2126 metastatic colorectal cancer patients scheduled to receive cetuximab. Infusion reactions were examined in 2006 patients with adequate safety data.


RESULTS
Infusion reactions of any grade occurred in 114 patients (5.7%), including Grade 3-4 infusion reactions in 22 patients (1.1%). Premedications were antihistamine plus corticosteroid (88.9% of patients with infusion reactions), antihistamine alone (9.2%) or corticosteroid alone (1.1%). In 95 patients (83.3%), infusion reactions occurred after the first dose. Twenty of the 22 Grade 3-4 infusion reactions occurred within 1 h of the first dose (the timing of the infusion reaction was unknown in one patient while another infusion reaction occurred after the fourth dose). Infusion reactions resolved in 111/114 patients (97.4%) while one patient recovered with sequelae, one patient died and one patient failed to recover within the follow-up period. Thirteen patients (15.7% of patients with infusion reactions) with Grade 1-2 infusion reactions showed recurrence after readministration of cetuximab; the recurrent infusion reactions were less severe than the initial reactions.


CONCLUSIONS
Grade 3-4 infusion reactions occurred in 1.1% of colorectal cancer patients, and most occurred within 1 h of receiving the first dose of cetuximab. Therefore, patients should be carefully observed following cetuximab infusion, especially during the first hour after the first infusion.
Department of Gastroenterology, Saitama Cancer Center, Kitaadachi-gun, Saitama k-yamaguchi@cancer-c.pref.saitama.jp.
Kensei
K
Yamaguchi
Department of Surgical Oncology, The University of Tokyo, Bunkyo-ku, Tokyo.
Toshiaki
T
Watanabe
Department of Medical Oncology, Kinki University, Osakasayama, Osaka Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Osaka.
Taroh
T
Satoh
Department of Surgical Oncology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo.
Megumi
M
Ishiguro
Bristol-Myers K.K., Shinjuku-ku, Tokyo.
Makiko
M
Izawa
Merck Serono Co., Ltd., Meguro-ku, Tokyo.
Shogo
S
Inoshiri
Department of Surgical Oncology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo.
Kenichi
K
Sugihara
Misawa City Hospital, Misawa, Aomori, Japan.
Yuh
Y
Sakata
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D044466:Asian People / Q000706:statistics & numerical data*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004342:Drug Hypersensitivity / Q000175:diagnosis / Q000517:prevention & control*; D005260:Female; D006633:Histamine Antagonists / Q000008:administration & dosage; D006801:Humans; D015994:Incidence; D007262:Infusions, Intravenous; D007564:Japan; D008297:Male; D008875:Middle Aged; D011292:Premedication / Q000379:methods; D011446:Prospective Studies; D012042:Registries; D012720:Severity of Illness Index; D013997:Time Factors
D000305:Adrenal Cortex Hormones; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D006633:Histamine Antagonists; D000068818:Cetuximab
cetuximab; chemotherapy; colorectal cancer; infusion reaction