Kwuio 2010-3-29 11:22
FDA核准5天療程的Decitabine處方用於治療骨髓發育不良症候群
作者：Yael Waknine
出處：WebMD醫學新聞
March 15, 2010 — 美國食品藥物管理局(FDA)核准5天療程的decitabine (商品名Dacogen，Eisai製藥公司)注射劑處方，用於治療骨髓發育不良症候群(myelodysplastic syndromes，MDS)病患；Decitabine是唯一獲得核准用於此種處方的低甲基試劑(hypomethylating agent)。
MDS是一種可能致命的骨髓疾病，會影響功能性血球的生產，而且，會隨著時間惡化成急性骨髓性白血症(acute myelogenous leukemia)，美國每年有約10,000到15,000例新診斷案例。
相較於原本核准的處方：以15 mg/m2劑量、連續靜脈輸注3小時以上，每療程3天，每6週治療一次，新核准的decitabine門診病患劑量：以20-mg/m2劑量、連續靜脈輸注1小時以上，每療程5天，每4週治療一次，新核准的處方可以減少輸注時間。
FDA的核准是根據3個開放標籤、單一群組、多中心研究的資料，研究對象是有任何法國-美國-英國亞型的MDS病患。
根據國際工作小組2000年版準則的結果顯示，病患達到的整體反應率為16% (完全緩解有15%；部分緩解有1%)，達到反應時間的中位數為162天，反應期間之中位數為443天。
嚴重副作用主要是嗜中性白血球減少症(37%)、血小板過低(24%)以及貧血(22%)。
FDA建議，病患需至少治療4個療程；若欲達到完全緩解或部分緩解可能需要更多療程。在開始治療前，應進行肝指數以及血清肌酸酐檢查；每次療程開始前應進行至少一次的全血球計數以及血小板計數，以監測反應和毒性。
在第1次和第2次療程時，比較會發生骨髓抑制以及嗜中性白血球減少症惡化，這可能不代表MDS惡化，當出現骨髓抑制時，需將後續的decitabine療程延後到恢復為止(絕對嗜中性白血球數量達≧1000/μL；血小板數量達≧50,000/μL)。
FDA Approves 5-Day Dosing Regimen for Decitabine for Myelodysplastic Syndromes
By Yael Waknine
Medscape Medical News
March 15, 2010 — The US Food and Drug Administration (FDA) has approved a 5-day dosing regimen for decitabine (Dacogen, Eisai, Inc) for injection in the treatment of patients with myelodysplastic syndromes (MDS). Decitabine is the only hypomethylating agent approved for this dosing regimen.
MDS is a potentially life-threatening group of bone marrow diseases that alter the production of functional blood cells and can, over time, progress to acute myelogenous leukemia. Between 10,000 and 15,000 new cases are diagnosed in the United States each year.
The new decitabine outpatient dosing option offers a decreased infusion time — a 20-mg/m2 dose is administered as a continuous intravenous infusion over 1 hour for 5 days per cycle every 4 weeks compared with the previously approved regimen of 15 mg/m2 continuous intravenous infusion given over 3 hours for 3 days per cycle every 6 weeks.
FDA approval was based on data from 3 open-label, single-group, multicenter studies of patients with MDS with any of the French-American-British subtypes.
Results based on International Working Group 2000 criteria showed that patients achieved an overall response rate of 16% (complete remission, 15%; partial response, 1%). Median time to response was 162 days, with a median duration of 443 days.
Serious adverse events most commonly reported included neutropenia (37%), thrombocytopenia (24%), and anemia (22%).
The FDA advises that patients be treated for a minimum of 4 cycles; more cycles may be required for a complete or partial response. Liver chemistries and serum creatinine should be obtained before initiation of therapy; complete blood and platelet counts should be performed at least once before each dosing cycle to monitor response and toxicity.
Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles and may not indicate MDS progression. In the presence of myelosuppression, subsequent decitabine treatment cycles should be delayed until recovery occurs (absolute neutrophil count ? 1000/μL; platelets ? 50,000/μL).