RESUMO
PURPOSE: Irinotecan is active against a variety of malignancies; however, severe diarrhea limits its usefulness. In our phase I study, the intravenous formulation of irinotecan was administered orally daily for 5 days for 2 consecutive weeks (repeated every 21 days) to children with refractory solid tumors. Our objectives were to determine the maximum-tolerated dose (MTD), dose-limiting toxicity, and pharmacokinetics of oral irinotecan and to evaluate whether coadministration of cefixime (8 mg/kg/d beginning 5 days before irinotecan and continuing throughout the course) ameliorates irinotecan-induced diarrhea. PATIENTS AND METHODS: In separate cohorts, irinotecan doses were escalated from 15 to 45 mg/m2/d without cefixime and then from 45 to 60 and 75 mg/m2/d with cefixime. RESULTS: Without cefixime, diarrhea was dose limiting at irinotecan 45 mg/m2/d. Myelotoxicity was not significant at any dose. The MTD was 40 mg/m2/d without cefixime but 60 mg/m2/d with cefixime. Systemic exposure to SN-38 at the MTD was significantly higher with cefixime than without cefixime (mean SN-38 area under the curve: 19.5 ng x h/mL; standard deviation [SD], 6.8 ng x h/mL v 10.4 ng x h/mL; SD, 4.3 ng x h/mL, respectively; P = .030). CONCLUSION: Cefixime administered with oral irinotecan is well tolerated in children and allows greater dose escalation of irinotecan. Because diarrhea is a major adverse effect of both intravenous and oral irinotecan, further evaluation of the use of cefixime to ameliorate this adverse effect is warranted.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Camptotecina/análogos & derivados , Cefixima/administração & dosagem , Diarreia/prevenção & controle , Neoplasias/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Antineoplásicos Fitogênicos/farmacocinética , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/farmacocinética , Criança , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Diarreia/induzido quimicamente , Fezes/enzimologia , Feminino , Glucuronidase/metabolismo , Humanos , Irinotecano , Lactonas/farmacocinética , Masculino , Índice de Gravidade de DoençaRESUMO
We describe 3 pediatric patients with cancer who had clinical and radiographic evidence of pneumonitis and for whom cultures of bronchoalveolar lavage fluid specimens yielded Ureaplasma urealyticum. Two of the patients died; for the surviving patient, clinical improvement coincided temporally with administration of erythromycin. Immunocompromised patients with pneumonitis of unclear etiology should have respiratory secretions cultured for mycoplasmas and should receive empiric therapy that includes a macrolide antibiotic.