D Arnold1, T Höhler2, C Dittrich3, F Lordick4, T Seufferlein5, J Riemann6, E Wöll7, T Herrmann8, A Zubel9, H-J Schmoll10. 1. Department of Oncology and Hematology, Martin-Luther-University Halle-Wittenberg, Halle. 2. Johannes-Gutenberg University Hospital, Mainz, Germany. 3. ACR-ITR VIEnna and LBI-ACR VIEnna, Kaiser Franz Josef-Spital, Vienna, Austria. 4. Klinikum rechts der Isar, Technische Universitaet, Muenchen. 5. Universitaets-Klinikum, Ulm. 6. Klinikum der Stadt Ludwigshafen, Ludwigshafen, Germany. 7. University Hospital Innsbruck, Innsbruck, Austria. 8. Department of Internal Medicine IV and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg. 9. Clinical Research and Development, Merck KGaA, Darmstadt, Germany. 10. Department of Oncology and Hematology, Martin-Luther-University Halle-Wittenberg, Halle. Electronic address: hans-joachim.schmoll@medizin.uni-halle.de.
Abstract
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. PATIENTS AND 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. CONCLUSION: This protocol is well tolerated and shows promising efficacy supporting further investigation.
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. PATIENTS AND 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. CONCLUSION: This protocol is well tolerated and shows promising efficacy supporting further investigation.
Authors: Eric Assenat; Francoise Desseigne; Simon Thezenas; Frédéric Viret; Laurent Mineur; Andrew Kramar; Emmanuelle Samalin; Fabienne Portales; Frédéric Bibeau; Evelyne Crapez-Lopez; Jean Pierre Bleuse; Marc Ychou Journal: Oncologist Date: 2011-10-20
Authors: Jaafar Bennouna; Marion Deslandres; Helene Senellart; Cecile de Labareyre; Rodrigo Ruiz-Soto; Claire Wixon; Jeff Botbyl; A Benjamin Suttle; Jean-Pierre Delord Journal: Invest New Drugs Date: 2014-09-24 Impact factor: 3.850