Cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric cancer: a phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO).
BACKGROUND
Cetuximab enhances the efficacy of chemotherapy in several cancer types. This trial assessed the activity of cetuximab and chemotherapy in advanced gastric cancer.


METHODS
Patients with previously untreated, metastatic, gastric cancer received cetuximab 400 mg m(-2) at first infusion followed by weekly infusions of 250 mg m(-2) combined with FUFOX (oxaliplatin 50 mg m(-2), 5-FU 2000 mg m(-2), and DL-folinic acid 200 mg m(-2) d1, 8, 15 and 22 qd36). The primary endpoint was tumour response.


RESULTS
Overall, 52 patients were enrolled. The most common grade 3/4 toxicities were diarrhoea (33%), and skin toxicity (24%). Efficacy was evaluable in 46 patients who showed a response rate of 65% (CI 95%: 50-79%) including four complete responses. Time to progression (TTP) was 7.6 months (CI 95%: 5.0-10.1 months) and overall survival (OS) was 9.5 months (CI 95%: 7.9-11.1 months). Epidermal growth factor receptor (EGFR) was detectable in 60% of tumours but showed no correlation with treatment outcome. A KRAS mutation was found in only 1 of 32 (3%) tumour samples analysed.


CONCLUSIONS
Cetuximab plus FUFOX showed an interesting high response rate in metastatic gastric cancer. Cetuximab plus platinum-fluoropyrimidine chemotherapy is at present being investigated in a phase III randomised controlled trial.
Lordick
F
F
Klinikum rechts der Isar, 3rd Medical Department, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, Germany. f.lordick@klinikum-braunschweig.de
Luber
B
B
Lorenzen
S
S
Hegewisch-Becker
S
S
Folprecht
G
G
Wöll
E
E
Decker
T
T
Endlicher
E
E
Röthling
N
N
Schuster
T
T
Keller
G
G
Fend
F
F
Peschel
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068818:Cetuximab; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D018631:ras Proteins / Q000235:genetics
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D000077150:Oxaliplatin; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil