The phase 3 trial HOVON-50 was designed to evaluate the effect of thalidomide during induction treatment and as maintenance in patients with multiple myeloma who were transplant candidates. A total of 556 patients was randomly assigned to arm A: 3 cycles of vincristine, adriamycin, and dexamethasone, or to arm B: thalidomide 200 mg orally, days 1 to 28 plus adriamycin and dexamethasone. After induction therapy and stem cell mobilization, patients were to receive high-dose melphalan, 200 mg/m 2 , followed by maintenance with ␣-interferon (arm A) or thalidomide 50 mg daily (arm B). Thalidomide significantly improved overall response rate as well as quality of the response before and after high dose melphalan. Best overall response rate on protocol was 88% and 79% (P ؍ .005), at least very good partial remission 66% and 54% (P ؍ .005), and complete remission 31% and 23% (P ؍ .04), respectively, in favor of the thalidomide arm. Thalidomide also significantly improved event-free survival from median 22 months to 34 months (P < .001), and prolonged progression free from median 25 months to 34 months (P < .001). Median survival was longer in the thalidomide arm, 73 versus 60 months; however, this difference was not significant (P ؍ .77). Patients randomized to thalidomide had strongly reduced survival after relapse. This trial was registered on www. controlled-trials.com as ISRCTN06413384.
The human vitamin K requirement is not known precisely, but the minimal requirement is often assumed to be between 0.5 and 1 x g/kg body weight. In the present study we addressed the question to what extent circulating vitamin K concentrations are influenced by the form in which the vitamer is consumed.The experimental group consisted of five healthy volunteers who received phylloquinone after an overnight fast. On the first day of three successive weeks the participants consumed 1 mg (22 pmol) phylloquinone, either in the form of a pharmaceutical preparation (Konakion"), or in the form of spinach + butter, or as spinach without added fat. Circulating phylloquinone levels after spinach with and without butter were substantially lower (75-and 24.3-fold respectively) than those after taking the pharmaceutical concentrate. Moreover, the absorption of phylloquinone from the vegetables was 1.5 times slower than from Konakion. In a second experiment in the same five volunteers it was shown that relatively high amounts of menaquinone-4 enter the circulation after the consumption of butter enriched with this vitamer. It is concluded that the bioavailability of membrane-bound phylloquinone is extremely poor and may depend on other food components, notably fat. The bioavailability of dietary vitamin K (phylloquinone + menaquinones) is lower than generally assumed, and depends on the form in which the vitamin is ingested. These new insights may lead to a revision of the recommended daily intake for vitamin K.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.