International randomized phase III study of elacytarabine versus investigator choice in patients with relapsed/refractory acute myeloid leukemia.

PURPOSE: Most patients with acute myeloid leukemia (AML) eventually experience relapse. Relapsed/refractory AML has a dismal prognosis and currently available treatment options are generally ineffective. The objective of this large, international, randomized clinical trial was to investigate the efficacy of elacytarabine, a novel elaidic acid ester of cytarabine, versus the investigator's choice of one of seven commonly used AML salvage regimens, including high-dose cytarabine, multiagent chemotherapy, hypomethylating agents, hydroxyurea, and supportive care. PATIENTS AND METHODS: A total of 381 patients with relapsed/refractory AML were treated in North America, Europe, and Australia. Investigators selected a control treatment for individual patients before random assignment. The primary end point was overall survival (OS). RESULTS: There were no significant differences in OS (3.5 v 3.3 months), response rate (23% v 21%), or relapse-free survival (5.1 v 3.7 months) between the elacytarabine and control arms, respectively. There was no significant difference in OS among any of the investigator's choice regimens. Prolonged survival was only achieved in a few patients in both study arms whose disease responded and who underwent allogeneic stem-cell transplantation. CONCLUSION: Neither elacytarabine nor any of the seven alternative treatment regimens provided clinically meaningful benefit to these patients. OS in both study arms and for all treatments was extremely poor. Novel agents, novel clinical trial designs, and novel strategies of drug development are all desperately needed for this patient population.

Cadence and performance in elite cyclists.

Many studies have attempted to describe the optimal cadence in cycling. However, the effect on performance has received little attention. The aim of the present study was therefore to examine the effect of cadence on performance during prolonged cycling (approximately 30 min). Fourteen male elite cyclists performed two or five time trials at different cadences [60, 80, 100, 120 rpm or freely chosen cadence (FCC)]. The total work was the same between the time trials, and the subjects were instructed to complete each time trial as fast as possible by adjusting the workload with buttons mounted on the handlebar. Accumulated work and cadence was visualised on a monitor. Oxygen uptake was measured continuously and blood lactate concentration every fifth minute. Compared to 80 rpm, finishing times at 60, 100 and 120 rpm were 3.5, 1.7 and 10.2% slower (P<0.05). Finishing time at FCC (mean 90 rpm) was indistinguishable from 80 and 100 rpm. Gross efficiency at 80 rpm was 2.9, 2.3, 3.4 and 12.3% larger than at 60, FCC, 100 and 120 rpm, respectively (P<0.05). The maximal energy turnover rate was 1.7% higher at 100 than at 80 rpm (P<0.05). This could not, however, compensate for the 3.4% lower efficiency at 100 rpm. This study demonstrated that elite cyclists perform best at their most efficient cadence despite the maximal energy turnover rate being larger at a higher cadence.

The most economical cadence increases with increasing workload.

Several studies have suggested that the most economical cadence in cycling increases with increasing workload. However, none of these studies have been able to demonstrate this relationship with experimental data. The purpose of this study was to test the hypothesis that the most economical cadence in elite cyclists increases with increasing workload and to explore the effect of cadence on performance. Six elite road cyclists performed submaximal and maximal tests at four different cadences (60, 80, 100 and 120 rpm) on separate days. Respiratory data was measured at 0, 50, 125, 200, 275 and 350 W during the submaximal test and at the end of the maximal test. The maximal test was carried out as an incremental test, conducted to reveal differences in maximal oxygen uptake and time to exhaustion (short-term performance) between cadences. The results showed that the lowest oxygen uptake, i.e. the best work economy, shifted from 60 rpm at 0 W to 80 rpm at 350 W ( P<0.05). No difference was found in maximal oxygen uptake among cadences ( P>0.05), while the best performance was attained at the same cadence that elicited the best work economy (80 rpm) at 350 W ( P<0.05). This study demonstrated that the most economical cadence increases with increasing workload in elite cyclists. It was further shown that work economy and performance are related during short efforts (approximately 5 min) over a wide range of cadences.