Aims: Data on long-term efficacy of bosentan in unselected idiopathic pulmonary arterial hypertension(IPAH) patients are lacking. We aimed to describe the long-term outcome of consecutive IPAH patients treated first-l...Aims: Data on long-term efficacy of bosentan in unselected idiopathic pulmonary arterial hypertension(IPAH) patients are lacking. We aimed to describe the long-term outcome of consecutive IPAH patients treated first-line with bosentan. Methods and results: A retrospective analysis of 103 consecutive New York Heart Association functional class III/IV IPAH patients treated with bosentan at our centre between November 1999 and May 2004 was performed. The 6-minute walk distance(6MWD) and haemodynamics were assessed at baseline and after 4 and 12 months. Mean follow-up was 24±15 months. At 4 months, significant improvements in exercise capacity and haemodynamics were observed and persisted up to 1 year. Overall survival estimates were 90 and 87%and event-free status(survival without transplantation, prostanoid initiation, or hospitalization for right heart failure) estimates were 61 and 44%at 1 and 2 years, respectively. Forty-five(44%) patients required prostanoid therapy during follow-up. The 6MWD and the right atrial pressure at baseline and the 6MWD, the increase in 6MWD, and the decrease in pulmonary resistance after 4 months of treatment were associated with long-term outcomes. Conclusion: In our series of consecutive IPAH patients treated with bosentan, improvements in exercise capacity and haemodynamics were similar to those observed in previous randomized trials. However, on the basis of local criteria, many patients required the addition of prostanoid therapy during follow-up.展开更多
BACKGROUND: Intravenous bolus fluorouracil plus leucovorin is the standard adjuvant treatment for colon cancer. The oral fluoropyrimidine capecitabine is an established alternative to bolus fluorouracil plus leucovori...BACKGROUND: Intravenous bolus fluorouracil plus leucovorin is the standard adjuvant treatment for colon cancer. The oral fluoropyrimidine capecitabine is an established alternative to bolus fluorouracil plus leucovorin as first-line treatment for metastatic colorectal cancer. We evaluated capecitabine in the adjuvant setting. METHODS: We randomly assigned a total of 1987 patients with resected stage III colon cancer to receive either oral capecitabine (1004 patients) or bolus fluorouracil plus leucovorin (Mayo Clinic regimen; 983 patients) over a period of 24 weeks. The primary efficacy end point was at least equivalence in disease-free survival; the primary safety end point was the incidence of grade 3 or 4 toxic effects due to fluoropyrimidines. RESULTS: Disease-free survival in the capecitabine group was at least equivalent to that in the fluorouracil-plus-leucovorin group (in the intention-to-treat analysis, P < 0.001 for the comparison of the upper limit of the hazard ratio with the noninferiority margin of 1.20). Capecitabine improved relapse-free survival (hazard ratio, 0.86; 95 percent confidence interval, 0.74 to 0.99; P=0.04) and was associated with significantly fewer adverse events than fluorouracil plus leucovorin (P< 0.001). CONCLUSIONS: Oral capecitabine is an effective alternative to intravenous fluorouracil plus leucovorin in the adjuvant treatment of colon cancer.展开更多
文摘Aims: Data on long-term efficacy of bosentan in unselected idiopathic pulmonary arterial hypertension(IPAH) patients are lacking. We aimed to describe the long-term outcome of consecutive IPAH patients treated first-line with bosentan. Methods and results: A retrospective analysis of 103 consecutive New York Heart Association functional class III/IV IPAH patients treated with bosentan at our centre between November 1999 and May 2004 was performed. The 6-minute walk distance(6MWD) and haemodynamics were assessed at baseline and after 4 and 12 months. Mean follow-up was 24±15 months. At 4 months, significant improvements in exercise capacity and haemodynamics were observed and persisted up to 1 year. Overall survival estimates were 90 and 87%and event-free status(survival without transplantation, prostanoid initiation, or hospitalization for right heart failure) estimates were 61 and 44%at 1 and 2 years, respectively. Forty-five(44%) patients required prostanoid therapy during follow-up. The 6MWD and the right atrial pressure at baseline and the 6MWD, the increase in 6MWD, and the decrease in pulmonary resistance after 4 months of treatment were associated with long-term outcomes. Conclusion: In our series of consecutive IPAH patients treated with bosentan, improvements in exercise capacity and haemodynamics were similar to those observed in previous randomized trials. However, on the basis of local criteria, many patients required the addition of prostanoid therapy during follow-up.
文摘BACKGROUND: Intravenous bolus fluorouracil plus leucovorin is the standard adjuvant treatment for colon cancer. The oral fluoropyrimidine capecitabine is an established alternative to bolus fluorouracil plus leucovorin as first-line treatment for metastatic colorectal cancer. We evaluated capecitabine in the adjuvant setting. METHODS: We randomly assigned a total of 1987 patients with resected stage III colon cancer to receive either oral capecitabine (1004 patients) or bolus fluorouracil plus leucovorin (Mayo Clinic regimen; 983 patients) over a period of 24 weeks. The primary efficacy end point was at least equivalence in disease-free survival; the primary safety end point was the incidence of grade 3 or 4 toxic effects due to fluoropyrimidines. RESULTS: Disease-free survival in the capecitabine group was at least equivalent to that in the fluorouracil-plus-leucovorin group (in the intention-to-treat analysis, P < 0.001 for the comparison of the upper limit of the hazard ratio with the noninferiority margin of 1.20). Capecitabine improved relapse-free survival (hazard ratio, 0.86; 95 percent confidence interval, 0.74 to 0.99; P=0.04) and was associated with significantly fewer adverse events than fluorouracil plus leucovorin (P< 0.001). CONCLUSIONS: Oral capecitabine is an effective alternative to intravenous fluorouracil plus leucovorin in the adjuvant treatment of colon cancer.
