Fluorouracil, leucovorin and irinotecan associated with aflibercept can induce microscopic colitis in metastatic colorectal cancer patients.
Aflibercept is a recombinant fusion protein that acts as a soluble decoy receptor for vascular endothelial growth factor (VEGF). This molecule binds to all isoforms of VEGF-A as well as VEGF-B and placental growth factor, preventing them from activating their respective receptors. Aflibercept is used for the treatment of metastatic colorectal cancer (mCRC) in association with irinotecan. For reasons that remain to be elucidated, the addition of aflibercept to irinotecan-based chemotherapy increases the incidence of grade 3-4 diarrhea. We performed systematic colonic biopsies in three patients with grade 3 diarrhea after introduction of fluorouracil, leucovorin, irinotecan and aflibercept treatment for mCRC. For each patient, the diarrhea necessitated treatment discontinuation. Colonoscopy showed normal colonic mucosa. However, histopathological examination of the biopsies performed in these three patients revealed typical features of microscopic colitis. All three patients were treated with budesonide and mesalazine, leading to rapid regression of clinical symptoms. Chemotherapy was reintroduced in all patients, with only mild, grade 1 diarrhea under mesalazine and budesonide treatment. These are the first observations of aflibercept-induced microscopic colitis, and support the use of specific treatment on top of anti-diarrheal treatment in case of important digestive adverse events.
INSERM UMR866, Dijon, France. fghiringhelli@cgfl.fr.|Faculté de Médecine, Université de Bourgogne, Dijon, France. fghiringhelli@cgfl.fr.|Department of Medical Oncology, Centre Georges François Leclerc, 1 rue du Professeur Marion, 21000, Dijon, France. fghiringhelli@cgfl.fr.
François
F
Ghiringhelli
Department of Medical Oncology, Centre Georges François Leclerc, 1 rue du Professeur Marion, 21000, Dijon, France.
Julie
J
Vincent
Department of Pathology, Centre Georges François Leclerc, Dijon, France.
Françoise
F
Beltjens
Department of Medical Oncology, Centre Georges François Leclerc, 1 rue du Professeur Marion, 21000, Dijon, France.
Leila
L
Bengrine
INSERM UMR866, Dijon, France. sladoire@cgfl.fr.|Faculté de Médecine, Université de Bourgogne, Dijon, France. sladoire@cgfl.fr.|Department of Medical Oncology, Centre Georges François Leclerc, 1 rue du Professeur Marion, 21000, Dijon, France. sladoire@cgfl.fr.
Sylvain
S
Ladoire
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D046728:Colitis, Microscopic / Q000139:chemically induced* / Q000175:diagnosis; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage / Q000009:adverse effects*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects*
D011993:Recombinant Fusion Proteins; C533178:aflibercept; D000077146:Irinotecan; D040262:Receptors, Vascular Endothelial Growth Factor; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
Adverse event; Aflibercept; Colitis; Colorectal cancer