[Nervous tumors of the infratemporal fossa]. / Les tumeurs nerveuses de la fosse infra-temporale.

Six cases of neurogenic tumors developing in the infratemporal fossa are reported. These are neuromas or neurofibromas in 5 cases and meningioma in 1 case only. The first 4 cases are primary tumors of the infratemporal fossa, while the last 2 tumors have developed into the temporal fossa from neighboring lesions. Computed tomography and RMI are irreplaceable techniques to assess the extension of such tumors and their connection with the neighboring organs, and to guide the treatment, which must be surgical whenever possible. Complete exeresis of the tumor is difficult. These examinations are also essential for follow-up and for the early detection of possible recurrence.

High-dose cytosine arabinoside and mitoxantrone in previously-treated acute leukemia patients.

35 patients with refractory or relapsed acute leukemia received salvage chemotherapy using high-dose cytosine arabinoside 2 g/m2 intravenously for 3 hours every 12 h, in 8 doses, followed by continuous infusion of mitoxantrone 12 mg/m2/day for 2 d. 9 patients had acute myeloblastic leukemia (AML), (4 relapsed, 5 refractory), 20 had acute lymphoblastic leukemia (ALL) (11 relapsed, 9 refractory) and 6 had chronic myelogenous leukemia (CML) in the blastic phase (BP). 4 out of 9 AML and 16 out of 20 ALL achieved complete remission. Median survival was 6 months for all patients and 10 months for responders. A short (1.5 months) chronic phase was achieved in 3 patients with CML. The main toxic effect was hematologic. A pharmacokinetic study was performed on mitoxantrone. No correlation was found with clinical response. The combination of mitoxantrone and ara-C is an effective antileukemic regimen, especially in ALL.

Population pharmacokinetics of mitoxantrone performed by a NONMEM method.

To date, the pharmacokinetics of mitoxantrone (1,4-dihydroxy-5,8-bis[[2-[(2- hydroxyethyl)amino]ethyl]amino]anthraquinone) has been described either by an open two- or three-compartment model, showing high interindividual variability. In order to evaluate this variability, residual intraindividual variability, and measurement error, we carried out a population study. A sensitive HPLC method allowed analysis of blood samples drawn from 21 patients with breast cancer or acute nonlymphocytic leukemia. Individual data treatment (22 kinetics) using weighted nonlinear least squares regression confirmed the huge interindividual variability whatever the administration protocol of mitoxantrone: bi- or tri-exponential models fitted the data. The NONMEM population method used herein describes all concentration-time curves by a single three-compartment model, considering biphasic kinetics as fragmentary data. Residual intraindividual variability was 21.4%. Population mean values (+/- interindividual SD) of clearance, terminal half-life, and total volume of distribution were, respectively, 23.40 (+/- 10.76) L/h, 46.87 (+/- 12.18) h, and 385.49 (+/- 196.60) L. These results are of particular interest in clinical routines to calculate dosage regimens by Bayesian estimation methods.

A limited sampling procedure for estimating adriamycin pharmacokinetics in cancer patients.

The aim of this study was to find a procedure allowing estimation of individual pharmacokinetic parameters for adriamycin with minimal cost and disturbance for the patient. Twenty-five patients with breast cancer were treated by short infusion of adriamycin at a dose of 12 mg m-2 week-1 (41 courses). Population characteristics were determined on 15 randomly chosen courses (10 patients, group I) in order to define two optimal sampling times (26 min and 24 h) and to perform Bayesian estimation on the remaining 26 courses (17 patients, group II). For patients of group II, Bayesian estimation (BE) associated with a reduced sub-optimal sampling protocol (20 min and 24 h) was compared with maximum likelihood estimation (MLE), the classical procedure. Regression analysis of clearance values obtained after BE versus MLE indicated a high correlation coefficient (r = 0.969) with the slope (a = 0.991 +/- 0.085) and the intercept (b = 2.271 +/- 4.810) close to 1 and 0 respectively. This original method is thus valid to measure accurately adriamycin clearance; it improves patient comfort and can be used routinely.