Phase I/II study of preoperative cetuximab, capecitabine, and external beam radiotherapy in patients with rectal cancer.
BACKGROUND
To assess the safety and preliminary efficacy of concurrent radiotherapy, capecitabine, and cetuximab in the preoperative treatment of patients with rectal cancer.


METHODS
Forty patients with rectal cancer (T3-T4, and/or N+, endorectal ultrasound) received preoperative radiotherapy (1.8 Gy, 5 days/week for 5 weeks, total dose 45 Gy, three-dimensional conformal technique) in combination with cetuximab [initial dose 400 mg/m(2) intravenous given 1 week before the beginning of radiation followed by 250 mg/m(2)/week for 5 weeks] and capecitabine for the duration of radiotherapy (650 mg/m(2) orally twice daily, first dose level; 825 mg/m(2) twice daily, second dose level).


RESULTS
Four and six patients were treated at the first and second dose level of capecitabine, respectively. No dose-limiting toxicity occurred. Thirty additional patients were treated with capecitabine at 825 mg/m(2) twice daily. The most frequent grade 1/2 side-effects were acneiform rash (87%), diarrhea (65%), and fatigue (57%). Grade 3 diarrhea was found in 15%. Three grade 4 toxic effects were recorded: one myocardial infarction, one pulmonary embolism, and one pulmonary infection with sepsis. Two patients (5%) had a pathological complete response.


CONCLUSIONS
Preoperative radiotherapy in combination with capecitabine and cetuximab is feasible with some patients achieving pathological downstaging.
Machiels
J-P
JP
Clinique des Pathologies Tumorales du Côlon et du Rectum, Centre du Cancer, Université catholique de Louvain, Cliniques universitaires Saint-Luc, 10 avenue Hippocrate, 1200 Brussels, Belgium. jean-pascal.machiels@onco.ucl.ac.be
Sempoux
C
C
Scalliet
P
P
Coche
J-C
JC
Humblet
Y
Y
Van Cutsem
E
E
Kerger
J
J
Canon
J-L
JL
Peeters
M
M
Aydin
S
S
Laurent
S
S
Kartheuser
A
A
Coster
B
B
Roels
S
S
Daisne
J-F
JF
Honhon
B
B
Duck
L
L
Kirkove
C
C
Bonny
M-A
MA
Haustermans
K
K
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D000068818:Cetuximab; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D020266:Radiotherapy, Conformal / Q000379:methods*; D012004:Rectal Neoplasms / Q000628:therapy*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000069287:Capecitabine; D000068818:Cetuximab; D005472:Fluorouracil