title: Pharmacokinetic profile of cetuximab (Erbitux) alone and in combination with irinotecan in patients with advanced EGFR-positive adenocarcinoma.
abstract: This trial assessed pharmacokinetic interactions between cetuximab and irinotecan. Patients were placed in either in group A (irinotecan 350 mg/m2/3 weeks and 400 mg/m2 cetuximab at week 2 then 250 mg/m2/week) or group B (cetuximab weekly starting week 1 then irinotecan starting week 4). Patient plasma or serum samples from each treatment arm were analysed using HPLC and ELISA. Among 14 patients, compartmental model showed no significant differences in mean plasma AUC at week 1 versus week 4 for irinotecan (44,388 versus 39,800 microg/ml/h) and cetuximab (20,441 versus 23,363 microg/ml/h), respectively. Half-lifes (standard deviations) for irinotecan were 16.02 (+/-8.41) h at week 1 and 13.99 (+/-2.14) h at week 4, and for cetuximab 106 (+/-32) at week 3 and 111 (+/-30) h at week 4. Mean concentration-versus-time profiles either alone or in combination were superimposable for cetuximab and irinotecan. From this study, we conclude that there is no evidence of pharmacokinetic interaction between irinotecan and cetuximab.
authors.affiliation: Department of Medicine and Department of Clinical Biochemistry, Institut Gustave-Roussy, Villejuif, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Delbaldo
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Pierga
authors.forename: Véronique
authors.initials: V
authors.lastname: Dieras
authors.forename: Sandrine
authors.initials: S
authors.lastname: Faivre
authors.forename: Valérie
authors.initials: V
authors.lastname: Laurence
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Vedovato
authors.forename: Marc
authors.initials: M
authors.lastname: Bonnay
authors.forename: Matthias
authors.initials: M
authors.lastname: Mueser
authors.forename: Arno
authors.initials: A
authors.lastname: Nolting
authors.forename: Andreas
authors.initials: A
authors.lastname: Kovar
authors.forename: Eric
authors.initials: E
authors.lastname: Raymond
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000077146:Irinotecan; D066246:ErbB Receptors; D000068818:Cetuximab; D002166:Camptothecin