High-dose dexamethasone plus antihistamine prevents colorectal cancer patients treated with modified FOLFOX6 from hypersensitivity reactions induced by oxaliplatin.
BACKGROUND
Oxaliplatin is a third-generation platinum compound and a key agent for the management of colorectal cancer. Patients treated with oxaliplatin are at risk for hypersensitivity reactions. We designed a modified premedication regimen to prevent oxaliplatin-related hypersensitivity reactions and assessed if this approach is effective.


METHODS
A retrospective cohort study of patients with advanced colorectal cancer who received modified FOLFOX6 (mFOLFOX6) was performed. Patients received routine premedication with dexamethasone 8 mg and granisetron 3 mg for the first five cycles of mFOLFOX6. From the sixth cycle onward, cohort 1 received the same premedication, and cohort 2 received modified premedication (diphenhydramine 50 mg orally, followed by dexamethasone 20 mg, granisetron 3 mg, and famotidine 20 mg). We compared the incidence of hypersensitivity reactions, duration of treatment, and reasons for treatment withdrawal between the two cohorts.


RESULTS
A total of 181 patients were studied (cohort 1, 81; cohort 2, 100). Hypersensitivity reactions developed in 16 patients (20%) in cohort 1 and 7 (7.0%) in cohort 2 (P = 0.0153). The median number of cycles increased from 9 in cohort 1 to 12 in cohort 2. Apart from progressive disease, neurotoxicity was the reason for discontinuing treatment in 20% of the patients in cohort 1, as compared with 53% in cohort 2.


CONCLUSIONS
Increased doses of dexamethasone and antihistamine significantly reduced oxaliplatin-related hypersensitivity reactions. This effective approach should be considered for all patients who receive FOLFOX, allowing treatment to be completed as planned.
Division of Pharmacotherapy, Kinki University School of Pharmacy, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
Yasuhiro
Y
Kidera
Taroh
T
Satoh
Shinya
S
Ueda
Wataru
W
Okamoto
Isamu
I
Okamoto
Soichi
S
Fumita
Kimio
K
Yonesaka
Hidetoshi
H
Hayashi
Chihiro
C
Makimura
Kunio
K
Okamoto
Hidemi
H
Kiyota
Junji
J
Tsurutani
Masaki
M
Miyazaki
Masahiro
M
Yoshinaga
Kimiko
K
Fujiwara
Yuzuru
Y
Yamazoe
Kenzo
K
Moriyama
Masanobu
M
Tsubaki
Yasutaka
Y
Chiba
Shozo
S
Nishida
Kazuhiko
K
Nakagawa
D000230:Adenocarcinoma / Q000188:drug therapy*; D018926:Anti-Allergic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003888:Desensitization, Immunologic; D003907:Dexamethasone / Q000008:administration & dosage; D004342:Drug Hypersensitivity / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006633:Histamine Antagonists / Q000008:administration & dosage*; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000077150:Oxaliplatin; D011292:Premedication; D012189:Retrospective Studies
D018926:Anti-Allergic Agents; D006633:Histamine Antagonists; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003907:Dexamethasone; D002955:Leucovorin; D005472:Fluorouracil
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