Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie.
BACKGROUND
This study assessed the activity of the mAb cetuximab in combination with cisplatin and 5-fluorouracil (5-FU) in advanced esophageal squamous cell carcinoma.


METHODS
For a maximum of six 29-day cycles, patients received cisplatin 100 mg/m(2), day 1, plus 5-FU 1000 mg/m(2), days 1-5 (CF), either alone or in combination with cetuximab (CET-CF; 400 mg/m(2) initial dose followed by 250 mg/m(2) weekly thereafter). The primary end point was tumor response. Tumor material was obtained for analysis of KRAS mutation status.


RESULTS
Sixty-two eligible patients were included, 32 receiving CET-CF and 30 CF. Cetuximab did not exacerbate grade 3/4 toxicity, except for rash (6% versus 0%) and diarrhea (16% versus 0%). The overall response rate according to RECIST criteria was 19% and 13% and the disease control rate 75% and 57% for the CET-CF and CF arms, respectively. With a median follow-up of 21.5 months, the median progression-free survival was 5.9 and 3.6 months and median overall survival 9.5 and 5.5 months for CET-CF and CF, respectively. No KRAS codon 12/13 tumor mutations were identified in 37 evaluated samples.


CONCLUSIONS
Cetuximab can be safely combined with CF chemotherapy and may increase the efficacy of standard CF chemotherapy.
Lorenzen
S
S
Third Department of Internal Medicine (Hematology/Medical Oncology), Technical University of Munich, Munich. florian.lordick@med.uni-heidelberg.de
Schuster
T
T
Porschen
R
R
Al-Batran
S-E
SE
Hofheinz
R
R
Thuss-Patience
P
P
Moehler
M
M
Grabowski
P
P
Arnold
D
D
Greten
T
T
Müller
L
L
Röthling
N
N
Peschel
C
C
Langer
R
R
Lordick
F
F
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D000068818:Cetuximab; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D018592:Cross-Over Studies; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab; D002945:Cisplatin; D005472:Fluorouracil