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【medical-news】阿扎胞苷：第一个延长高危MDS患者
December 11, 2007 — In patients with high-risk myelodysplastic syndrome (MDS), azacitidine (Vidaza, Pharmion) should be considered first-line treatment, according to the largest trial of this disease, which showed better survival than with conventional care, including chemotherapy. This was the conclusion from a phase 3 trial reported by Pierre Fenaux, MD, from Hôpital Avicenne, in Paris, France, at the American Society of Hematology 49th Annual Meeting in Atlanta, Georgia.
The results show "an important survival benefit," Dr. Fenaux said. Patients on azacitidine had a median overall survival of 24.4 months, compared with 15 months with conventional care (P = .0001; hazard ratio, 0.58 ). The 2-year survival rate was 50.8% with azacitidine, compared with 26.2% with conventional care.
"These results are unexpectedly fantastic," said Azra Raza MD, from the University of Massachusetts, in Worcester, who was not involved in the study. They are "good enough to be proclaimed from the rooftops," she told Medscape Oncology in an interview. "Even using high-dose chemotherapy, with which we have managed to get some complete responses, we have never managed to prolong overall survival or affect the natural course of the disease."
MDS is a particularly difficult disease to treat, Dr. Fenaux told the meeting. The only curative treatment is bone marrow transplantation, but this is applicable only in a small number of cases. Azactidine was approved 3 years ago, the first drug ever for MDS, but the trials at that time showed a trend toward survival benefit, and "we wanted to make this much clearer," Dr. Fenaux explained. The company-sponsored phase 3 trial he was presenting involved 358 patients, and "is the largest trial to date in MDS," he said.
The trial compared azacitidine with conventional care, which included chemotherapy in 40% of cases. The remainder of patients either received low-dose cytarabine or they were treated with transfusions, antibiotics, and granulocyte-colony stimulating factor (G-CSF) for neutropenic infections.
As well as the significant difference in overall survival, all the secondary end points were also in favor of azacitidine, including disease progression, complete and partial responses, and hematological responses. Among the azacitidine group, 45% of patients achieved transfusion independence, compared with 11% on conventional care. The superiority of azacitidine over conventional care was seen in all subgroups of patients, regardless of age and the chemotherapy regimen used, and this finding was "highly consistent," Dr. Fenaux said.
This trial is the first in MDS patients to demonstrate a significant overall survival advantage, "thus altering the natural disease course," Dr. Fenaux said. "Azacitidine now represents the standard of care in high-risk MDS," he concluded, "and all new drugs will be compared with it or combined with it," he said.
Dr. Raza agreed that azacitidine should now be a standard therapy for this disease. "Every patient should be given a chance to have this drug," she told Medscape Oncology. "These results will change the way we treat this disease," she predicted. "At present, about 50% of MDS patients are not treated at all because some doctors feel that these patients are elderly with comorbidities...and they see no point in treating with toxic chemotherapy regimens if they don't prolong survival even when they achieve a complete response. But there is now very little to justify this complacent approach, because these data show that azacitidine does prolong survival." The median survival was 24 months, so some patients are living longer than this. "For an 89-year old patient, this can make a huge difference; he [or she] may live to see his [or her] grandson graduating, for example." High-risk MDS is "universally fatal," Dr. Raza emphasized, with survival of only 5 months or so without any treatment.
There will be a paradigm shift in the treatment of MDS, Dr. Raza predicted. In addition to azacitidine, there is a similar hypomethylating agent already approved — decitabine (Dacogen, MGI Pharma), which has shown equal if not better efficacy, Dr. Raza said, although there are no survival data as yet. This might come out of the ongoing trial in Europe, she said, although in this trial decitabine is being used at a high dose, which might not show it at its best; there are data suggesting that "less is more" with these agents.
An interesting point from this study, which might be applicable to other hematological malignancies, is that the prolonged survival was achieved despite the fact that only 10% to 13% of patients achieved a complete response. This suggests a new paradigm, Dr. Raza commented: "We have always thought that we need to get rid of every last cell and achieve a complete response in order to prolong survival."
Dr. Fenaux reports receiving research funding from Pharmion; Dr. Raza reports receiving research funding and being on the speakers bureau for Pharmion.
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作者:admin@医学,生命科学 2011-06-29 18:23
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