Abstract
Mitotane (MIT) has been recently found to be able to reverse <i>in vitro</i> the multi drug resistance mediated by the MDR-1/P-glycoprotein, providing the rationale for its clinical use in combination with non specific cytotoxic drugs in the treatment of ACC. We report on the association of MIT to a etoposide, adriamycin and cisplatin chemotherapeutic regimen (EAP) in 7 patients (pts) with advanced/metastatic ACC. 3 of them were previously submitted to radical surgery and recurred after 29, 11, 7 months, respectively. 4 pts presented with locally advanced or metastatic disease ab <i>initio</i>, maximal debulking was pursued in 2 and primary tumor was judged as inoperable in the remaining.PtAge(yr) SexSurgical resectionDisease localizationsHormone secretionN° of coursesTumor responseResponse duration145/MAadrenal+liverF5SD6 months229/FAliver+adrenalF +An8PR7 months318/FRAloog+mediastinumF6PR27 months447/FRAliver+lung+adrenalF+An6SD3 months562/F−Iiver+adrenalAn4SD10 months644/FRAlungAn53 months746/F−adrenalAn 3 P−F: cortisol; An: androgens; SD: stable disease; PR: partial response; P: progression; Horm: Hormone; secret; secretion. All pts had clinical and/or biochemical evidence of hormone hypersecretion. A median of 5 EAP cycles was administered. Oral MIT was continuously assumed at the planned dose of 4cg/daily, or at the maximum tolerated dose, 3g in 2 pts and 2g in the others. More than 50% reduction of tumor mass (PR) was obtained in 3 pts, stable disease in 3 and progressive disease in 1. The toxicity of EAP + MIT was mild to moderate and only 2 patients experienced a grade 3 hemathologic toxicity (WHO criteria). The 3 pts who had partial response survived 12, 48+, and 14 months, respectively; the pts who showed stable disease survived 8+, 9 and 24 months, respectively. The association of MIT to EAP chemotherapy scheme appears to be feasible with acceptable toxicity.
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