Hypomagnesemia is a reliable predictor for efficacy of anti-EGFR monoclonal antibody used in combination with first-line chemotherapy for metastatic colorectal cancer.
OBJECTIVE
Anti-EGFR monoclonal antibody is effective for KRAS wild-type metastatic colorectal cancer (mCRC), but frequently causes several adverse reactions, including hypomagnesemia and skin disorders. The present study was designed to investigate the relationship between the incidence of adverse reactions and therapeutic effects in mCRC patients receiving anti-EGFR monoclonal antibody in combination with first-line chemotherapy.


METHODS
Forty-three mCRC patients who received cetuximab or panitumumab between April 2012 and December 2015 were the subjects of the present study. All patients were pretreated with oral minocycline in combination with skin treatment using moisturizer for prevention of skin rash. Hypomagnesemia and acneiform rash were graded according to the Common Terminology Criteria for Adverse Events, version 3.0. Overall response rate (ORR) and time to treatment failure (TTF) were compared between patients with and without these adverse events.


RESULTS
The incidence rates of hypomagnesemia and acneiform rash were 32.6 % (grade 1: 20.9 %, grade 2: 11.6 %) and 93.0 % (grade 1: 41.9 %, grade 2: 41.9 %, grade 3: 9.3 %), respectively. ORR was significantly higher in patients with hypomagnesemia than in those without it (71.4 vs 34.5 %, P = 0.048). Median TTF tended to be longer, though not significantly, in patients with hypomagnesemia than in those without it. However, no significant difference in both ORR and median TTF was observed between patients with and without acneiform rash.


CONCLUSIONS
Hypomagnesemia may become a predicting factor for therapeutic effects of anti-EGFR monoclonal antibody in mCRC patients.
Department of Pharmacy, Gifu University Hospital, Gifu, 501-1194, Japan. h_fujii@gifu-u.ac.jp.
Hironori
H
Fujii
Department of Pharmacy, Gifu University Hospital, Gifu, 501-1194, Japan.
Hirotoshi
H
Iihara
Department of Pharmacy, Gifu University Hospital, Gifu, 501-1194, Japan.
Akio
A
Suzuki
Department of Pharmacy, Gifu University Hospital, Gifu, 501-1194, Japan.
Ryo
R
Kobayashi
Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, 501-1193, Japan.
Nobuhisa
N
Matsuhashi
Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, 501-1193, Japan.
Takao
T
Takahashi
Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, 501-1193, Japan.
Kazuhiro
K
Yoshida
Department of Pharmacy, Gifu University Hospital, Gifu, 501-1194, Japan.
Yoshinori
Y
Itoh
D017486:Acneiform Eruptions / Q000139:chemically induced*; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000068818:Cetuximab / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008274:Magnesium / Q000008:administration & dosage / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000077544:Panitumumab; D011237:Predictive Value of Tests; D066066:Response Evaluation Criteria in Solid Tumors; D017211:Treatment Failure
D000911:Antibodies, Monoclonal; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D008274:Magnesium; D000068818:Cetuximab
Acneiform rash; Anti-EGFR monoclonal antibody; Hypomagnesemia; Metastatic colorectal cancer; Overall response rate; Time to treatment failure