Pharmacokinetic profile of cetuximab (Erbitux) alone and in combination with irinotecan in patients with advanced EGFR-positive adenocarcinoma.
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.
Delbaldo
Catherine
C
Department of Medicine and Department of Clinical Biochemistry, Institut Gustave-Roussy, Villejuif, France.
Pierga
Jean-Yves
JY
Dieras
Véronique
V
Faivre
Sandrine
S
Laurence
Valérie
V
Vedovato
Jean-Claude
JC
Bonnay
Marc
M
Mueser
Matthias
M
Nolting
Arno
A
Kovar
Andreas
A
Raymond
Eric
E
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
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000077146:Irinotecan; D066246:ErbB Receptors; D000068818:Cetuximab; D002166:Camptothecin