vicky3 2009-10-14 13:15
FDA核准Pralatrexate用於治療反應不佳的T細胞淋巴瘤
作者：Yael Waknine
出處：WebMD醫學新聞
September 26, 2009 — 美國食品藥物管理局（FDA）已經同意加速核准以孤兒藥的狀態讓pralatrexate注射劑（Folotyn，Allos治療有限公司）作為單一治療用於再發或對治療反應不佳的T細胞淋巴瘤。這個相對罕見且經常是侵襲性的非何杰金氏淋巴瘤，在美國的病例每年不到9,500件。
奧瑪哈內布拉斯加大學內科部Joe Shapiro醫學教授James O. Armitage醫師在公司的新聞稿中表示，侵襲性週邊T細胞淋巴瘤是經常被忽略的一群疾病。現在有第一個獲得FDA核可用於治療再發或對治療反應不佳週邊T細胞淋巴瘤的治療是令人興奮的。
FDA的決定是根據一項開放標記、單一組別、多中心跨國臨床研究（PROPEL；共115位病患）的優先審查數據，這些病患都罹患再發性或對治療反應不佳的週邊T細胞淋巴瘤，且接受pralatrexate（每週30 mg/m2）靜脈推注3~5分鐘，持續6週，7個星期為一週期，直到疾病惡化或無法耐受的毒性。
這些病患也接受每8~10週的1 mg維生素B12肌肉注射，以及每天口服1~1.25 mg葉酸來降低與治療相關的血液毒性及黏膜炎。
研究結果顯示，109位可評估的病患中，有29位（27%）的腫瘤縮小，大部分有反應的病患（66%）在第一個週期內的治療就達到療效。
根據FDA表示，腫瘤縮小被合理地認為可能預測臨床好處，例如癌症病患存活時間延長。需要針對pralatrexate進行更多的研究，以進一步釐清並且描述這些好處。
研究中最常被報告的不良事件包括黏膜炎（70%）、血小板數目低下（41%）、噁心（40%）與疲倦（36%）；嚴重程度的（第三或四級）的不良反應，包括血小板數目低下（33%）、黏膜炎（21%）、中性球數目低下（20%）與貧血（20%）。
因為pralatrexate會造成胎兒傷害，在治療期間，女性應該避免懷孕，而已經懷孕的女性應該被告知對於胎兒潛在的風險。
治療中重度腎臟功能受損患者時，建議小心且仔細地追蹤腎臟功能。併用從腎臟排除的藥物（例如probencid、非類固醇抗發炎藥物、以及trimethoprim/sulfamethaxazole）可能會使排除速度變慢。
發生第二級以上黏膜炎或嚴重（第三級以上）肝功能異常患者，應該暫停使用pralatrexate或調整劑量。
FDA Approves Pralatrexate for Relapsed/Refractory T-Cell Lymphoma
By Yael Waknine
Medscape Medical News
September 26, 2009 — The US Food and Drug Administration (FDA) has granted accelerated approval and orphan drug status for pralatrexate injection (Folotyn, Allos Therapeutics, Inc) as a single agent for the treatment of relapsed or refractory peripheral T-cell lymphoma. The relatively rare and often aggressive type of non-Hodgkin's lymphoma occurs in fewer than 9500 US patients annually.
"Aggressive peripheral T-cell lymphomas have been a largely ignored group of diseases," said James O. Armitage, MD, Joe Shapiro Professor of Medicine, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, in a company news release. "It is exciting to have the first FDA-approved therapy for relapsed or refractory peripheral T-cell lymphoma."
The FDA's action was based on a priority review of data from an open-label, single-group, multicenter, international clinical trial (PROPEL; n = 115), in which patients with relapsed or refractory peripheral T-cell lymphoma received pralatrexate at 30 mg/m2 once weekly by intravenous push during 3 to 5 minutes for 6 weeks in 7-week cycles until disease progression or unacceptable toxicity.
Patients also received 1 mg of vitamin B12 intramuscularly every 8 to 10 weeks and 1 to 1.25 mg of folic acid orally on a daily basis to reduce treatment-related hematologic toxicity and mucositis.
Results showed that 29 (27%) of 109 evaluable patients demonstrated a reduction in tumor size, with the majority of responders (66%) achieving this effect within the first cycle of therapy.
According to the FDA, tumor shrinkage is considered reasonably likely to predict a clinical benefit such as extended survival in cancer patients. Additional studies of pralatrexate are being required to further verify and describe these advantages.
Adverse events most commonly reported in the study included mucositis (70%), thrombocytopenia (41%), nausea (40%), and fatigue (36%); severe (grade 3/4) adverse events were thrombocytopenia (33%), mucositis (21%), neutropenia (20%), and anemia (20%).
Because pralatrexate can cause fetal harm, women should avoid becoming pregnant during therapy, and pregnant women should be advised of the potential risks to the fetus.
Caution and careful monitoring is advised when treating patients with moderate to severe renal impairment. Coadministration of drugs subject to renal clearance (eg, probenecid, nonsteroidal anti-inflammatory drugs, and trimethoprim/sulfamethaxazole) may result in delayed elimination.
Pralatrexate dosing should be omitted or modified for patients who develop grade 2 or greater mucositis or severe (grade ? 3) liver function test abnormalities.