title: Lack of long-lasting effects of mitotane adjuvant therapy in a mouse xenograft model of adrenocortical carcinoma.
abstract: Mitotane is a widely used drug in the therapy of adrenocortical carcinoma (ACC). It is important to set up preclinical protocols to study the possible synergistic effects of its association with new drugs for ACC therapy. We assessed the efficacy of different routes of administration of mitotane (i.p. and oral) in inhibiting growth of H295R ACC cell xenografts in an adjuvant setting. Both formulations of mitotane could inhibit H295R xenografts growth only at short times after carcinoma cells inoculation, even though plasma mitotane levels approached or fell within the therapeutic range in humans. Our results show that mitotane adjuvant therapy is inadequate to antagonize long-term growth of H295R cancer cells xenografts and that care should then be taken in the design of preclinical protocols to evaluate the performance of new drugs in association with mitotane.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire CNRS, Valbonne, France; Associated International Laboratory (LIA) NEOGENEX CNRS, Valbonne, France; University of Nice-Sophia-Antipolis, Valbonne, France.
authors.forename: Mabrouka
authors.initials: M
authors.lastname: Doghman
authors.forename: Enzo
authors.initials: E
authors.lastname: Lalli
mesh_terms: D000284:Administration, Oral; D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D007274:Injections, Intraperitoneal; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008939:Mitotane / Q000008:administration & dosage* / Q000493:pharmacokinetics; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D018931:Antineoplastic Agents, Hormonal; D008939:Mitotane
keywords: ACC; Adrenal cortex; Cancer; Mitotane; NOD/SCID; Xenografts; adrenocortical carcinoma; non-obese diabetic/severe combined immunodeficiency