RESUMEN
PURPOSE: The aim of this study was to determine (i) the maximum tolerated dose (MTD) of liposomal doxorubicin (L-DOX) and paclitaxel (DP), (ii) the MTD of DP plus valspodar (DPV) and (iii) pharmacokinetic (PK) interactions of valspodar with L-DOX and paclitaxel. METHODS: Twenty-three patients with metastatic cancers received DP, followed 4 weeks later by DPV. Dose levels of DP were (mg/m2 for L-DOX/paclitaxel): 30/135 (n = 7), 30/150 (n = 4), 35/150 (n = 8) and 40/150 (n = 4). Dose levels of DPV were 15/70 (n = 10) and 15/60 (n = 10). Serial, paired PK studies were performed. RESULTS: The MTD of DP was 40/150. For DPV at 15/70, five of 10 patients experienced grade 4 neutropenia. In the next cohort, a reduced dose of 15/60 was well tolerated. Valspodar produced reversible grade 3 ataxia in seven patients, requiring dose reduction from 5 to 4 mg/kg. Paired PK studies indicated no interaction between L-DOX and valspodar, and a 49% increase in the median half-life of paclitaxel. Two partial and one minor remissions were noted. CONCLUSIONS: The use of valspodar necessitated dose reductions of DP, with neutropenia being dose limiting. Valspodar PK interactions were observed with paclitaxel but not L-DOX.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Neoplasias/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Ciclosporinas/administración & dosificación , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Interacciones Farmacológicas , Femenino , Humanos , Liposomas , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias/metabolismo , Paclitaxel/administración & dosificaciónRESUMEN
One hundred U.S. Air Force recruits were administered the cycle ergometry test to determine their aerobic fitness and timed on a 2-mile run before beginning the physical conditioning phase of training. The estimated oxygen consumption (vO2) was calculated for all trainees completing the ergometry test. The mean estimated vO2 for those successfully completing basic military training (BMT) on schedule was 27.95 +/- 1.74 ml/kg/minute, whereas the mean estimated vO2 for those not completing the program on schedule was 32.94 +/- 3.55 ml/kg/minute (not statistically different). For the 2-mile run, the times ranged from 14 minutes 17 seconds to 29 minutes 11 seconds. The mean run time for those completing BMT on schedule was 22 minutes 28.15 seconds +/- 25.79 seconds, compared to 21 minutes 19.46 seconds +/- 1 minute 26.30 seconds for those not completing the program on schedule (not statistically different). Neither relative risk nor chi-square calculations were statistically significant. No significant associations between run times or a passing cycle ergometry score at the beginning of BMT and successful completion of BMT were found.