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An international expanded access program was initiated to provide access to treatment with pemetrexed prior registration and reimbursement for malignant mesothelioma (MM). Chemonaïve and pretreated patients with inoperable MM of the pleura or peritoneum were eligible. This report describes the results obtained in German centers. Investigators could choose between three treatments: Pemetrexed 500 mg/m(2) alone (P) or in combination with cisplatin 75 mg/m(2) (PC) or carboplatin AUC 5 (PCb). From November 2002 to June 2004, a total of 567 patients (554 with pleural MM; 41% pretreated) were included. Of 548 evaluable patients with pleural MM, 191 received P, 137 PC and 220 PCb. Patients in the P group were more often pretreated (70%) and had worse performance status compared with the other groups. In the P, PC, and PCb groups overall response rate (ORR) was 16%, 24% and 18%, median time to progression (TTP) was 5.5, 8.2, and 6.9 months, and median overall survival (OS) was 8.7, 11.3 and 9.7 months respectively. Efficacy outcomes were better for chemonaïve than for pretreated patients, and P was less hematotoxic than PC or PCb. Treatment of pleural MM with pemetrexed alone or in combination with platinum was safe and active as first and second-line therapy., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Genotype G of hepatitis B virus (HBV) has only recently been discovered. This report describes the full-length sequence of genotype G HBV (designated 235/01) isolated in Germany from a chronic HBV carrier. The patient was hepatitis B e antigen-positive, had high HBV DNA levels of about 10(10) copies/ml serum, lacked a measurable anti-HBc response, and was coinfected with human immunodeficiency virus type 1. Genome 235/01 showed characteristic genotype G-specific features: stop codons at codon 2 and 28 of the pre-C region and insertion of 36 nucleotides at the 5' end of the C gene. It was nearly identical (< or = 99.7% identity) to both genotype G genomes (B1-89 and FR1 from France) described so far, suggesting either close epidemiological link among European genotype G isolates or high genetic stability of genotype G.

NK 611 is a new podophyllotoxin derivative in which a dimethyl amino group replaces a hydroxyl group at the sugar moiety of etoposide. This results in profound physico-chemical differences: NK 611 is much less hydrophobic than etoposide. Preclinical studies have shown that NK 611 is advantageous in terms of bioavailability and of the potency of its anticancer activity. A clinical phase I study was performed in cancer patients within the framework of the AIO. Additionally, its pharmacokinetics and pharmacodynamics were investigated. NK 611 was given to 26 patients at doses ranging from 60 to 140 mg/m2 [maximum tolerated dose (MTD) 120 mg/m2] in a 30-min infusion. Plasma and urine samples were collected from 25 patients and analyzed using a validated high-performance liquid chromatography (HPLC) assay procedure. The concentration versus time curve of total NK 611 in plasma samples was best described by a three-compartment model. The overall median pharmacokinetic values were as follows (ranges are given in parentheses): mean residence time (MRT) 16.5 (5.4-42.3)h, terminal half-life 14.0 (8.2-30.5)h, volume of distribution at steady state (V(ss)) 11.4 (7.9-18.1) l/m2 and plasma clearance (Cl(p)) 15.1 (3.6-36.4) ml min-1 m-2. The total systemic drug exposure, represented by the area under the curve (AUC), varied between 53.4 and 532.0 micrograms ml-1 h. The mean AUC (+/- SD) increased with the dose from 78.7 +/- 3.7 micrograms ml-1 h at 60 mg/m2 up to 202.8 +/- 157.2 micrograms ml-1 h at 120 mg/m2. The mean urinary excretion (UE) fraction of unchanged drug at 48 h after the end of the infusion varied between 3.0% and 25.8% of the total dose delivered. Analysis of ultrafiltrate samples showed a protein binding of approx.. 99%. The percentage reduction in white blood cells (WBC) and neutrophils (ANC) correlated with the dose, AUC, and AUC(free). The best relationship between the percentage of reduction in ANC and a pharmacokinetic parameter (AUC) took a nonlinear Hill-type form. The laboratory parameter for kidney or liver function did not correlate with the AUC. The variation of pharmacokinetic parameters within each dose level was profound. The reason for this pharmacological behavior remains unclear and should be investigated in further studies.