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Bendamustine has demonstrated clinical activity and a favorable safety profile as monotherapy or in combination with rituximab in lymphoid malignancies. As interventional trials do not always reflect clinical reality, we were interested in the treatment modalities and the outcome of bendamustine-based first-line therapy in patients with advanced indolent non-Hodgkin lymphoma (NHL) and mantle cell lymphoma (MCL) in routine practice. Between April 2010 and October 2011, 324 patients were enrolled in a prospective non-interventional multicenter study. Choice of the bendamustine regimen was at the treating physician's discretion. Effectiveness was assessed by best response. Mean age at onset of therapy was 69 years. The majority (94 %) of the patients was treated with bendamustine in combination with rituximab at a median bendamustine dose of 177 mg/m(2) per cycle. Most often, bendamustine was administered on days 1 and 2 (87 %) at 4-week intervals over a median of 6 cycles. Two hundred eighty-one patients qualified for evaluation of response. The overall response rate was 86 % (complete response 43 %, partial response 43 %, stable disease 10 %, progressive disease 4 %). Side effects of all grades were documented for 161 of the 323 patients (50 %), most frequently affecting blood/bone marrow (35 %). Fifty-four (17 %) patients experienced side effects of grade 3 (15 %) or grade 4 (2 %), and two patients grade 5 toxicities. Bendamustine-based first-line treatment of patients with advanced indolent NHL and MCL in clinical routine practice was assessed as effective and well tolerated in our study. Response was comparable to results from interventional clinical trials.

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BACKGROUND: The treatment of colorectal cancer with administration of a 2-h infusion of calcium folinate followed by a 24-h infusion of 5-fluorouracil (5-FU) is a standard therapy. Based on newly published data we have applied an infusion of both compounds, 5-FU and calcium folinate, mixed together in an ambulatory pump. PATIENT AND METHODS: We report on a patient suffering from metastatic rectal cancer. After first and second line chemotherapy we started third line chemotherapy consisting of calcium folinate (1,000 mg) and 5-FU (4,000 mg) mixed together in a total volume of 240 ml in an ambulatory pump and administered over a period of 24 h. After a total of 11 applications the patient developed a port thrombosis resistant to lysis with urokinase. The blocked catheter was surgically explanted and the firm material inside was analyzed. RESULTS: The material from inside the lumen of the catheter was analyzed using x-ray spectroscopy and a scanning electron microscopy. Both analyses confirmed that the isolated material is calcium carbonate. CONCLUSION: This case and the results of the analyses are in accordance with the described problems and results published earlier. A physical and/or chemical in vitro compatibility of 5-FU and calcium folinic acid, without validated clinical data is not sufficient to use this mixture in routine clinical practice.

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Treatment of acute viral hepatitis B is symptomatic, fulminant cases may require liver transplantation. In chronic hepatitis B interferon (IFN)-alpha will induce sustained response rates of 30-40%. Nucleoside analogues such as famciclovir or lamivudine appear to be promising for treatment in non-responders or cirrhotic and immunosuppressed patients. IFN-alpha may reduce the rate of chronic courses in acute hepatitis C infections. Chronic hepatitis C patients with elevated ALT activities, positive serum HCV RNA and portal or bridging fibrosis on biopsy are recommended for treatment with IFN-alpha. Sustained responses are observed in less than 20% of treated patients. Retreatment with IFN-alpha may be indicated in non-responders or in case of relapse. Combination therapy of IFN-alpha plus ribavirin may emerge as treatment of choice for patients with a relapse in the near future.

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A total of 37 patients with histologically confirmed chronic viral hepatitis B and presence of HBV-DNA and HBsAg in the serum were treated in a randomized, prospectively controlled multicenter trial either with recombinant IFN alpha-2b alone or a combination of IFN alpha-2b and recombinant IL-2. Twenty-two patients from group A were treated with 3 MU of IFN alpha-2b s.c. thrice weekly for 5 months. Starting at month 2 IL-2 was added: priming doses of 1.5 million CU were given s.c. on the first 2 days of each of the remaining 3 months, followed by maintenance doses of 0.3 million CU daily for 5 days per week. Fifteen patients from group B received 5 MU of IFN alpha-2b s.c. thrice weekly for 5 months. Five patients from group A (24%) and 4 patients from group B (28%) cleared HBV-DNA and HBeAg from the serum, and normalized elevated serum aminotransferase activities. The response rate in both groups did not differ significantly. Since side effects were more pronounced during combination therapy than in IFN alpha-2b monotherapy, it is suggested that treatment with IFN alpha-2b alone is preferable to a regimen of IFN alpha-2b/IL-2 applied according to the above schedule.

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Bone is a target organ of androgens. The mechanism by which these steroids exert their action within bone cells is still poorly understood. The metabolism of androstenedione, the major circulating androgen in women, was, therefore, assessed in osteoblast-like bone cells cultured from bone of 16 postmenopausal women (mean age, 69 yr; range, 56-80) and 3 elderly men (mean age, 71 yr; range, 69-73) undergoing total hip replacement. Each cell strain was incubated under standardized conditions with varying concentrations of [1,2,6,7-3H]androstenedione (0.05-5 microM). In every instance 5 alpha-reduced metabolites and 17 beta-hydroxysteroids were formed. There was no correlation between the volumetric density of the resected bone and androstenedione metabolism of the corresponding cultured bone cell strains. The apparent Km for the 5 alpha-reductase activity (sum of androstanedione and dihydrotestosterone) of all 19 cell strains was 0.7 +/- 0.1 microM (mean +/- SEM), and the apparent Km for 17 beta-hydroxysteroid dehydrogenase (sum of testosterone and dihydrotestosterone) was 2.3 +/- 0.8 microM (mean +/- SEM), values similar to those reported for other androgen target organs. Our results demonstrate that human osteoblast-like cells have the capacity to transform androstenedione into the more potent biological androgens testosterone and dihydrotestosterone. Since the Km values of both 5 alpha-reductase and 17 beta-hydroxysteroid dehydrogenase exceed the serum androstenedione concentration, the formation of testosterone and dihydrotestosterone appears to be mainly a function of substrate availability.

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