Oil spill management: elimination kinetics of PAHs in mussels (Mytilus edulis).

Efficient oil spill management in the marine environment requires the ability to predict the rate of loss of individual priority hydrocarbon compounds from marine organisms. Rate of elimination of polycyclic aromatic hydrocarbons (PAHs) from mussels decreases with increase in molecular weight and degree of alkylation.

Phase II randomized study of Plitidepsin (Aplidin), alone or in association with L-carnitine, in patients with unresectable advanced renal cell carcinoma.

This randomized phase II study evaluated two schedules of the marine compound Plitidepsin with or without co-administration of L-carnitine in patients with renal cell carcinoma. Patients had adequate performance status and organ function. The primary endpoint was the rate of disease control (no progression) at 12 weeks (RECIST). Other endpoints included the response rate and time dependent efficacy measures. The trial also assessed the efficacy of L-carnitine to prevent Plitidepsin-related toxicity. The two regimes given as 24 hour infusion every two weeks showed hints of antitumoral activity. Disease control at 12 weeks was 15.8% in Arm A (5mg/m2, no L-carnitine) and 11,1% in Arm B (7 mg/m2 with L-carnitine). Two partial responses were observed in Arm A (19 patients), none in Arm B (20 patients). Both schedules had the same progression-free interval (2.1 months). The median overall survival was 7.0 and 7.6 months. The safety profile was similar in both arms of the trial and adverse events were mainly mild to moderate (NCI CTC version 2.0). Increasing the dose to 7 mg/m2 did not increase the treatment efficacy but the incidence of transaminase and CPK elevations and serious AEs. Coadministration of L-carnitine did not prevent muscular toxicity or CPK-elevation associated with Plitidepsin.

Phase II study of rubitecan in recurrent or metastatic head and neck cancer.

PURPOSE: Rubitecan is an oral camptothecin analogue that has shown activity against a broad spectrum of human tumor xenografts and has been tested in several diseases. PATIENTS AND METHODS: In the present study, 19 patients with incurable, recurrent or metastatic head and neck cancer were treated with rubitecan at the initial dose of 1.5 mg/m(2) x 5 days per week. An appropriate dose modification program was set up according to the observed toxicities. RESULTS: Thirteen out of the 19 treated patients were formally evaluable for tumor response. Ten patients had a disease progression and three patients had a stabilization of disease as their best response. The mean duration of stable disease was 141 days. Median survival was 16 weeks (range 2-22 weeks). Three patients died during the study or less than a month after their last dose of study medication. Hematologic toxicity was serious in this study since four patients discontinued their participation because of severe anemia. The drug was also associated with grade 1-4 neutropenia, and with 1-3 thrombocytopenia. CONCLUSION: We conclude that rubitecan is not effective as a single-agent in recurrent or metastatic head and neck cancer with the doses and schedule used in this study.

Effects of feeding status on biliary PAH metabolite and biliverdin concentrations in plaice (Pleuronectes platessa).

Relationships between feeding status and the biliary concentrations of biliverdin and metabolites of polycyclic aromatic hydrocarbons (PAH) have been investigated in plaice (Pleuronectes platessa) from the Firth of Clyde, Scotland. Plaice were caught at three times of the day, and kept, without feeding, in tanks for up to 24h. The mean concentrations of biliary PAH metabolites 2-OH naphthalene, 1-OH pyrene and 3-OH benzo-[a]-pyrene (3-OH B[a]P) were found to increase slightly over a 24h non-feeding period (only significant for 3-OH benzo-[a]-pyrene). This effect was not observed for mean biliary concentrations of 1-OH phenanthrene. During this period of starvation, bile volume, total amounts of all PAH metabolites in the gall bladder, and biliary biliverdin concentrations all significantly increased. No significant relationships (P>0.05) were found between indicators of feeding status and individual PAH metabolite concentrations, confusing the rationale for normalisation of data to account for differences in feeding status between fish. Normalisation of PAH metabolite concentrations to biliverdin concentrations did not consistently reduce the variance of the metabolite data for fish sampled after the same starvation period. However, the variation between mean metabolite concentrations of fish suffering different starvation periods was reduced by biliverdin normalisation for most of the metabolites measured. It is therefore recommended that biliary PAH metabolite data should be presented as raw concentrations, except in cases where there may be significant differences in feeding status between groups of fish. In such instances biliverdin normalised data should also be reported and observational guides such as bile volume and stomach contents may aid in the interpretation of data.