Pharmacokinetic characterization of mitonafide in man.

The pharmacokinetic behavior of mitonafide after intravenous administration (1 h infusions) to patients (118-180 mg/m2) can be described by an open three compartment body model. Mitonafide distributes quasi-instantaneously in a central distribution volume of 102 l/m2 (median) from which it equilibrates with two peripheral compartments of 106 and 258 l/m2, respectively. Its disappearance from plasma is triexponential with half-lives of 0.28, 2.0 and 26.9 h, resulting in a clearance of 69 l/h/m2. This clearance is mainly due to the biotransformation of mitonafide leading among others to amonafide, N-acetyl-amonafide, and N-desmethyl-amonafide, which build up substantial concentrations in plasma. Their quantitative importance in terms of exposures (AUC) relative to the parent compound are 86, 197 and 28%, respectively. Terminal elimination from plasma proceeds with half-lives of 34.3, 17.6 and 27.5 h.

The role of combination cyclophosphamide, doxorubicin and cisplatin (CAP) chemotherapy in advanced non-small-cell lung cancer.

Thirty-one patients with non-small-cell lung cancer (NSCLC), stage III (T3 N2 M 0-1), were treated with cyclophosphamide (400 mg/m2), adriamycin (40 mg/m2) and cisplatin (60 mg/m2) (CAP) every 4 weeks for 8 cycles. Twenty-six patients were evaluable for response. Patients characteristics included: median age, 63 years; median performance status, 70% (range 60%-100%). One hundred and fifty-five cycles of chemotherapy were administered with a median of 5. There were 9 partial responses and 3 complete remissions, for an overall response rate of 46%. The median survival duration was 9 months, and 29% survived 1 year. CAP combination chemotherapy was well tolerated without nephrotoxicity, which can be imputed to the strong saline hydration given. Seventy percent of the patients did not experience emesis due to the antiemetic regimen used.

[Malignant hypereosinophilic syndrome. Report of an exceptional case (author's transl)]. / Síndrome hipereosinofílico maligno: presentación de un caso excepcional.

The case of a 43-year-old man with a highly malignant hypereosinophilic syndrome is reported. The condition is classified as such according to Hardy and Anderson's criteria, accepted by many other authors. Other diseases of known etiology which may present high levels of eosinophils in the peripheral blood, such as parasitosis, allergies, neoplasias, collagenosis, etc., were discounted beforehand. The difficulties in distinguishing between these diseases are discussed; they are often accompanied by clinical manifestations which also arise in very different conditions including eosinophilic leukemia, Engfeldt and Zetterström's eosinophilic collagenosis, Löffler's fibroplastic endocarditis, etc. A particularly striking feature of this condition is the formation of large tumor masses of mature eosinophils. They begin in various bones, which they destroy almost completely, and invade the surrounding tissues, destroying them as well. These tumors act similarly to malignant eosinophilic myelocytomas, a fact which has not been reported previously in the literature as far as we know. Although the eosinophils act as though they were neoplastic, they maintain the characteristics of mature cells, both cytomorphologically and ultrastructurally as well as cytochemically (consistently chloroacetate esterase negative). The tendency to diagnose eosinophilic leukemia solely on the basis of the malignancy of the condition and a tissue infiltration of eosinophils without determining the existence of cytologic and/or cytochemical anomalies of the cells showing them to be leukemic is discussed. The authors were unable to find any reports in the literature in which the eosinophils were presented with unmistakeably blastic cellular characteristics. Various nosologic considerations are offered.