Assuntos
Angioedema/complicações , Angioedema/tratamento farmacológico , Eosinofilia/complicações , Eosinofilia/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Angioedema/diagnóstico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Benzamidas , Neoplasias da Mama/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Diagnóstico Diferencial , Eosinofilia/diagnóstico , Feminino , Humanos , Mesilato de Imatinib , Pessoa de Meia-Idade , Piperazinas/efeitos adversos , Pirimidinas/efeitos adversos , RecidivaAssuntos
Lúpus Eritematoso Sistêmico/cirurgia , Nefrectomia/métodos , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Adulto , Resistência a Medicamentos , Feminino , Seguimentos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Injeções Intravenosas , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Infecções Oportunistas/etiologia , Troca Plasmática , Púrpura Trombocitopênica Trombótica/complicações , Púrpura Trombocitopênica Trombótica/cirurgia , Síndrome , Resultado do TratamentoRESUMO
A novel schema of intrapatient dose escalation was applied to determine a population-based maximum tolerated dose (pMTD) for irinotecan (CPT-11, Camptosar) and carboplatin (Paraplatin) in a phase I trial. A total of 74 patients with advanced solid tumors were enrolled with the following characteristics: men/women, 46/28; median age, 61 years; 51 patients with and 23 patients without prior chemotherapy; performance status of 0-1 (93%) and 2 (7%). Patients were started at dose level 1 with irinotecan at 200 mg/m2, and carboplatin at an area under the concentration-time curve (AUC) of 5 mg/mL x min, administered every 21 days. Depending on degree of toxicity observed, the dose for each patient in each subsequent cycle was determined according to a predetermined schema of dose levels. Individual maximum tolerated dose (iMTD) was determined for each patient. The pMTD was defined as the highest dose level for which the incidence of dose-limiting toxicity occurred in less than 33% of the patient population. The most common dose-limiting toxicity included neutropenia (58%), thrombocytopenia (15%), diarrhea (8%), and nausea/emesis (7%). The iMTD ranged from dose level-3 (irinotecan at 100 mg/m2 and carboplatin at an AUC of 4) to dose level 5 (irinotecan at 350 mg/m2 and carboplatin at AUC 6). The pMTD was determined to be dose level-1 and 1 for previously chemotherapy-treated and--untreated patients, respectively. Fifty-nine patients were assessable for response. Of note, a response rate of 40% was observed in 15 patients with relapsed small-cell lung cancer previously treated with platinum-based therapy. We recommend dose level 1 of irinotecan (200 mg/m2) and carboplatin (AUC 5) for chemotherapynaive patients, and dose level-1 of irinotecan (150 mg/m2) and carboplatin (AUC 5) for chemotherapy-treated patients in phase II trials.