Cetuximab in combination with weekly 5-fluorouracil/folinic acid and oxaliplatin (FUFOX) in untreated patients with advanced colorectal cancer: a phase Ib/II study of the AIO GI Group.
BACKGROUND
This two-part phase Ib/II study investigated the feasibility of administering cetuximab in combination with oxaliplatin and infusional 5-fluorouracil (5-FU)/folinic acid (FA) in a weekly schedule (AIO FUFOX protocol) as first-line treatment in patients with epidermal growth factor receptor-detectable advanced colorectal cancer.


METHODS
Cetuximab was administered weekly: 400 mg/m(2) initial dose, then 250 mg/m(2) and FUFOX: oxaliplatin 50 mg/m(2), FA 500 mg/m(2) and 5-FU as a 24-h infusion at either 1500 or 2000 mg/m(2) administered for 4 weeks followed by a 1-week rest (one cycle).


RESULTS
Dose-limiting toxicity (grade 3 diarrhea) occurred in 3 of 14 assessable patients receiving 5-FU at standard 2000 mg/m(2). This dose was administered to a further 25 patients. Cetuximab combined with FUFOX was generally well tolerated with the most common grade 3/4 adverse events being diarrhea (27%) and paresthesia (16%). The confirmed response rate for patients receiving 5-FU at standard 2000 mg/m(2) (N = 41) was 56%, with a median duration of 9.3 months. Median progression-free and overall survival times including all 49 patients were 8.1 (95% confidence interval 6.0-9.7) and 28.2 months, respectively. Cetuximab pharmacokinetics seemed not to be different for combination with FUFOX compared with cetuximab/irinotecan combinations.


CONCLUSIONS
This protocol is well tolerated and shows promising efficacy supporting further investigation.
Arnold
D
D
Department of Oncology and Hematology, Martin-Luther-University Halle-Wittenberg, Halle.
Höhler
T
T
Johannes-Gutenberg University Hospital, Mainz, Germany.
Dittrich
C
C
ACR-ITR VIEnna and LBI-ACR VIEnna, Kaiser Franz Josef-Spital, Vienna, Austria.
Lordick
F
F
Klinikum rechts der Isar, Technische Universitaet, Muenchen.
Seufferlein
T
T
Universitaets-Klinikum, Ulm.
Riemann
J
J
Klinikum der Stadt Ludwigshafen, Ludwigshafen, Germany.
Wöll
E
E
University Hospital Innsbruck, Innsbruck, Austria.
Herrmann
T
T
Department of Internal Medicine IV and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg.
Zubel
A
A
Clinical Research and Development, Merck KGaA, Darmstadt, Germany.
Schmoll
H-J
HJ
Department of Oncology and Hematology, Martin-Luther-University Halle-Wittenberg, Halle. Electronic address: hans-joachim.schmoll@medizin.uni-halle.de.
D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000096:biosynthesis; 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; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010349:Patient Compliance
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D066246:ErbB Receptors; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil