A clinical and pharmacological study of arsenic trioxide in advanced multiple myeloma patients.

We previously showed that arsenic trioxide (ATO) and melarsoprol may inhibit the growth of multiple myeloma (MM) cells in vitro and in vivo. We report here the administration of arsenic derivatives in 12 relapsing or refractory secretory MM patients. A total of 10 patients received ATO (eight in a continuous schedule, two discontinuously) and two received melarsoprol. The melarsoprol arm was prematurely closed due to toxicity. In the ATO arm, median duration of treatment was 38 days (9-54). Hepatic toxicity was grade 3 and 2 in one and eight patients, respectively. Other toxicities included neuropathy (n=2, grade 2), encephalitis (n=1, grade 3) and leuconeutropenia (n=4, grade 3). At 2 weeks after treatment initiation, mean serum concentration of arsenic was 1.11+/-0.16 micromol/l. No complete or partial remission was observed. A minor response (25-49% reduction of M protein in serum) and a stabilization of the M-protein level were observed in three and four patients, respectively. After ATO discontinuation, these responses were of short duration in all cases. ATO as a single agent did not produce any significant response in advanced MM patients despite sufficient arsenic exposure. Strategies to improve biodistribution, pharmacokinetic and efficacy of the drug as well as treatment combinations are needed.

[Implementation of a specific premedication protocol for tracheal intubation in the delivery room. Practice in two level-III hospitals]. / Impact d'un protocole de sédation avant intubation trachéale en salle de naissance. Pratiques dans deux centres de niveau III.

UNLABELLED: Tracheal intubation in neonates is a painful procedure performed daily in the delivery room despite the widespread development of noninvasive ventilation. Specific analgesia is not commonly performed. The objective of this observational study was to compare practices between two level-III centers: one with a specific protocol for premedication before tracheal intubation of newborns in the delivery room, the other without. RESULTS: One hundred and fifteen neonates were intubated in the delivery room and included over a 4-month period: 25% of them received specific premedication before intubation, exclusively in the center with the protocol. None of the extreme premature neonates (age≤28 gestational weeks) received analgosedation before the procedure. Nalbuphine, midazolam, and sufentanil were mainly used, via the intravenous or intrarectal route. Infants receiving a premedication were significantly heavier and had a greater gestational age than the others (1500 g [range, 1180-2260 g] vs. 1170 [range, 860-1680 g] P=0.003, and 31 GW [range, 29-34 GW] vs. 29 [range, 27-32 GW] P=0.014, respectively). Most pediatricians (85-100%) favored a specific protocol for sedation before tracheal intubation. Implementation of a specific protocol allows specific analgesia to be implemented for newborns undergoing tracheal intubation. Further studies should be conducted to determine the best strategies for pain management during tracheal intubation of neonates, especially in the delivery room.