美国FDA批准氮芥外用制剂VALCHLOR，每天一次凝胶局部施用，治疗患者以阶段IA和IB蕈样肉芽肿型皮肤T细胞淋巴瘤谁收到事先皮肤导向治疗（MF-CTCL）烷基化药物。Valchlor在美国被指定为孤儿药。 处方修改批准日期：2015年8月 公司：Actelion公司美国制药公司 VALCHLOR（氮芥 mechlorethamine）凝胶，局部使用 最初美国批准：1949年 作用机理 氮芥，也称为氮芥，是抑制快速增殖细胞的烷化剂。 适应症和用法 VALCHLOR是在患者中谁收到事先皮肤导向治疗阶段IA和IB蕈样肉芽肿型皮肤T细胞淋巴瘤的局部治疗所表示的烷基化的药物。 用法用量 对于只有局部皮肤使用 每日一次应用的薄膜对皮肤的受灾地区 剂型和规格 凝胶：0.016％w/w的氮芥（相当于0.02％氮芥HCl中）在60克管 禁忌症 严重过敏对氮芥 警告和注意事项 黏膜或眼外伤：VALCHLOR暴露于粘膜，特别是眼睛，可造成粘膜损伤可能是严重的。眼睛受伤可能会导致失明。立即冲洗至少15分钟，然后立即就医咨询。 二次曝光VALCHLOR：比其他病人的个人必须避免与VALCHLOR皮肤接触 皮炎：监测患者发红，肿胀，发炎，瘙痒，水疱，溃疡，和继发皮肤感染。停止治疗或减少剂量频率。 非黑色素瘤皮肤癌：治疗期间和治疗后监测患者。 胚胎 - 胎儿毒性：可引起胎儿造成伤害。告知潜在危险的妇女胎儿易燃凝胶：VALCHLOR是酒精类凝胶。避免引起火灾，火焰，吸烟，直到凝胶已干 不良反应 最常见的不良反应（≥5％）的皮炎，瘙痒，细菌性皮肤感染，皮肤溃疡或起泡，和色素沉着。 特殊人群中使用 哺乳母亲：请停止药物或哺乳。 完整处方资料附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f522cd6d-aa0f-4b44-92cc-ed952058eea0 氮芥外用软膏VALCHLOR(MECHLORETHAMINE HYDROCHLORIDE)GEL Valchlor (mechlorethamine) gel 0.016% is applied topically once a day to affected areas of the skin. Valchlor is the first and only FDA-approved topical formulation of mechlorethamine. CURRENT INDICATION In the US, Valchlor gel 0.016% is indicated for the topical treatment of stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL) in patients who have received prior skin-directed therapy. Regulatory review with the European health authorities is ongoing. AVAILABLE CLINICAL DATA The efficacy of Valchlor was assessed in a randomized, multicenter, observer-blind, non-inferiority trial of 260 patients. Patients were stratified based on Stage (IA vs IB and IIA) and then randomized to receive Valchlor gel 0.016% w/w of mechlorethamine (equivalent to 0.02% mechlorethamine HCl) or Aquaphor®-based mechlorethamine HCl 0.02% ointment (compounded mechlorethamine). Patients had received at least one prior skin-directed therapy. Qualifying prior therapies included topical corticosteroids, phototherapy, Targretin® gel, and topical nitrogen mustard. Patients were not required to be refractory to or intolerant of prior therapies. Treatments were applied topically on a daily basis for 12 months. 60% of the patients on the Valchlor arm and 48% of patients on the comparator arm achieved a response based on the Composite Assessment of Index Lesion Severity (CAILS) score. Valchlor was non-inferior to the comparator based on a CAILS overall response rate ratio of 1.24 (95% CI 0.98, 1.58). Complete responses constituted a minority of the CAILS or Severity Weighted Assessment Tool (SWAT) overall responses. The onset of CAILS overall response for both treatment arms showed a wide range from 1 to 11 months. The most common adverse reactions (≥5%) were dermatitis (56%), pruritus (20%), bacterial skin infection (11%), skin ulceration or blistering (6%), and skin hyperpigmentation (5%). These reactions may be moderately severe or severe. Elderly patients aged 65 and older may be more susceptible. Depending on severity, treatment reduction, suspension, or discontinuation may be required. VALCHLOR Rx Pharmacological Class: Nitrogen mustard. Active Ingredient(s): Mechlorethamine 0.016%; topical gel; contains propylene glycol, isopropyl alcohol. Company Actelion Pharmaceuticals Indication(s): Treatment of Stage IA and IB mycosis fungoides-type ­cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy. Pharmacology: Mechlorethamine, also known as nitrogen mustard, is an alkylating agent which inhibits rapidly proliferating cells. Clinical Trials: The efficacy of Valchlor was assessed in a randomized, multicenter, observer-blind, active-controlled, non-inferiority clinical trial involving 260 patients with Stage IA, IB, and IIA mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL) who had received ≥1 prior skin-directed therapy (eg, topical corticosteroids, phototherapy, Targretin gel, or topical nitrogen mustard). Patients were not required to be refractory to or intolerant of prior therapies. Patients were randomized (after stratification based on Stage IA vs. IB and IIA) to receive Valchlor (N=119) or Aquaphor-based ointment (N=123), both equivalent to 0.02% mechlorethamine. The study drug was to be topically applied once daily for 12 months, and concomitant use of topical corticosteroids was not permitted. Patients were evaluated monthly for the first 6 months, then every 2 months for the last 6 months using the Composite Assessment of Index Lesion Severity (CAILS) score. A response was defined as ≥50% reduction in baseline CAILS score, which was confirmed at the next visit ≥4 weeks later; a complete response was defined as a confirmed CAILS score of 0. Patients were also evaluated using the Severity Weighted Assessment Tool (SWAT). A response was defined as ≥50% reduction in baseline SWAT score, which was confirmed at the next visit ≥4 weeks later. At 12 months, 60% of patients treated with Valchlor and 48% of patients treated with the comparator achieved a response based on CAILS score. Valchlor was non-inferior to the comparator based on a CAILS overall response ratio of 1.24 (95% CI 0.98, 1.58). Complete responses constituted a minority of the CAILS or SWAT overall responses. The onset of CAILS overall response for both treatment arms showed a wide range from 1 to 11 months. Legal Classification: Rx Adults: Apply a thin film once daily to affected areas of the skin. Apply to completely dry skin ≥4 hours before or 30 minutes after showering or washing. Allow treated areas to completely dry for 5–10 minutes after applying. Wash hands thoroughly after application. Discontinue if any grade of skin ulceration, blistering, or moderately-to-severe, or severe dermatitis occur; restart at reduced frequency of once every 3 days upon improvement; if reintroduction is tolerated for at least 1 week, can increase to every other day for 1 week and then once daily if tolerated. Children: Not established. Warnings/Precautions: Mucosal (oral, nasal) or eye exposure; blindness and severe irreversible anterior eye injury may occur; immediately irrigate for ≥15 minutes with copious amounts of water. Secondary exposure; avoid direct skin contact with patient. Risk of dermatitis (eg, face, genitalia, anus, and intertriginous skin); monitor for redness, swelling, inflammation, itchiness, blisters, ulceration, and secondary skin infections. Monitor for nonmelanoma skin cancer during and after treatment. Flammable (avoid fire and flame until gel has dried). Pregnancy (Category D); may cause fetal harm. Nursing mothers: not recommended. Adverse Reaction(s) Dermatitis, pruritus, bacterial skin infection, skin ulceration or blistering, hyperpigmentation. How Supplied: Gel—60g LAST UPDATED: 11/25/2013 Valchlor（mechlorethamine，氮芥）凝胶是由CeptarisTherapeutics公司研发的一种注射用化疗药物，日前获得FDA批准通过，这种药物可以直接通过皮下注射药物mechlorethamine以治疗阿利贝尔氏病（T细胞淋巴瘤的一种）。而此前，mechlorethamine仅被允许通过静脉注射治疗。这也标志着公司与瑞士公司Actelion的价值2亿5千万美元里程碑协议的完成。公司表示将尽快将这种产品推上市场。 CeptarisTherapeutics公司是一家私营专业制药公司，8月26日该公司宣布，美国FDA批准其罕用药Valchlor（mechlorethamine，氮芥）凝胶用于局部治疗先前接受过皮肤治疗IA和IB阶段蕈样肉芽肿型皮肤T细胞淋巴瘤（CTCL）的患者。Valchlor是第一个也是唯一获得FDA批准的外用配方氮芥制剂。局部应用于皮肤，每天涂抹一次。 氮芥是一种化疗药，先前获准用于静脉注射治疗蕈样肉芽肿，最常见类型的CTCL。（美国）国家综合癌症网络（NCCN）目前推荐外用氮芥制剂用于治疗早期CTCL，在Valchlor获准前，尚没有获得FDA批准的外用氮芥制剂产品，只有药房配制的非标准化复合油质软膏或水质外用制剂。药房自配的复合制剂无需FDA审查批准，因此没有经过一个审查。 斯坦福大学医学院皮肤淋巴瘤多学科诊所主任、皮肤科和皮肤淋巴瘤研究教授PeterHaasJr指出：“本品获准是患者的福音。现在我们有充分对照的临床试验证据支持Valchlor在大多数先前作过治疗的IA和IB阶段CTCL患者有临床意义的应答。”