The liposomal formulation of amphotericin B (AmBisome) greatly reduces the acute and chronic side effects of the parent drug. The present study describes the pharmacokinetic characteristics of AmBisome applied to 10 patients at a dose of 2.8 to 3.0 mg/kg of body weight and compares them to the pharmacokinetics observed in 6 patients treated with amphotericin B deoxycholate at the standard dose of 1.0 mg/kg. Interpatient variabilities of amphotericin B peak concentrations (C max ) and areas under concentration-time curves (AUC) were 8-to 10-fold greater for patients treated with AmBisome than for patients treated with amphotericin B deoxycholate. At the threefold greater dose of AmBisome, median C max s were 8.4-fold higher (14.4 versus 1.7 g/ml) and median AUCs exceeded those observed with amphotericin B deoxycholate by 9-fold. This was in part explained by a 5.7-fold lower volume of distribution (0.42 liters/kg) in AmBisome-treated patients. The elimination of amphotericin B from serum was biphasic for both formulations. However, the apparent half-life of elimination was twofold shorter for AmBisome (P ‫؍‬ 0.03). Neither hemodialysis nor hemofiltration had a significant impact on AmBisome pharmacokinetics as analyzed in one patient. In conclusion, the liposomal formulation of amphotericin B significantly (P ‫؍‬ 0.001) reduces the volume of drug distribution, thereby allowing for greater drug concentrations in serum. The low toxicity of AmBisome therefore cannot readily be explained by its serum pharmacokinetics.

Combination chemotherapy with gemcitabine and cisplatin given on 2 out of 3 weeks is well tolerated and active in heavily pretreated patients with MBC, even after prior exposure to anthracyclines and taxanes.

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Application of amphotericin B in lipid emulsions (AmB/L) reduced membrane toxicity in vitro and decreased amphotericin B-associated toxic side effects in vivo when compared to that of amphotericin B applied in 5% glucose (AmB/G). Therefore, a comparative analysis of the pharmacological parameters of AmB/L and AmB/G was performed. Thirteen patients were analyzed, and nine of these patients received a subsequent treatment with AmB/G and AmB/L. In patients in both treatment groups amphotericin B showed a biphasic elimination from serum, with a prolonged terminal half-life of approximately 27 h. Patients treated with AmB/L showed significantly lower peak concentrations (44.2%; P = 0.008) and correspondingly lower area under the drug concentration-time curve (AUC) values (64.3%; P = 0.015) compared to the values for the same patients treated with AmB/G at a dose range of 0.6 to 1.5 mg/kg of body weight. The enhanced clearance of AmB/L may be due to a faster initial elimination of amphotericin B-lipid aggregates by the reticuloendothelial system. Lower peak concentrations and AUC values in serum and a correspondingly faster deposition of AmB/L in tissues may at least partly explain the lower toxicity of AmB/L. A comparative pharmacokinetic analysis with data for a single patient treated with AmB/L demonstrated that hemodialysis did not significantly affect the disposition of amphotericin B.

Background: Cure is rarely achieved in patients with advanced metastatic solid tumors, and quality of life including times without burdening therapies is an important endpoint. Metronomic oral cyclophosphamide (Cy) has been studied before and is a reasonable option. Patients and Methods: 24 patients with a mean age of 64.4 years (range 36–82 years) were studied. 18 patients had breast cancer, 4 prostate cancer, 1 uterine carcinoma, and 1 carcinoma of unknown primary. Results: All patients had advanced disease with a mean of 2 metastatic sites. Cy was given at a mean dosage of 52 mg daily. Time from diagnosis to start of Cy was 108.6 ± 7.6 months, and from occurrence of metastatic disease to Cy 45.8 ± 45.6 months. Patients had received a mean of 4.2 ± 2.1 prior regimens for metastatic disease. The mean time to treatment failure was 6.4 ± 5.4 months, and mean overall survival was 12.7 ± 7.3 months. Patients received 2.1 ± 1.4 further treatments upon progression. Main toxicities were grade 1 and 2 (n = 25); 3 patients had grade 3 nausea, leucopenia, and elevated gamma glutamyl transferase, respectively. Conclusion: Low-dose oral Cy is a reasonable, generally well tolerated, and inexpensive option for patients with advanced solid tumors.