6月13日，美国FDA批准Lymphoseek(锝99m tilmanocept) 注射剂一种新用途，这款药物是一种放射性诊断影像剂，用来帮助医生确定鳞状细胞癌已扩散至人体头部及颈部的程度。
2013年，Lymphoseek 被批准用来帮助鉴别乳腺癌及黑色素瘤患者体内离原发性肿瘤最近的淋巴结。
由于今天的批准，Lymphoseek现在可用来指导头颈癌患者最接近于癌症原发性肿瘤的淋巴结的检查，也叫前哨淋巴结活组织检查。这种新的适应症可以为癌症前哨淋巴结活组织检查阴性患者选择更加有限的淋巴结手术。
“对一些患有头颈癌的患者来说，排出原发性肿瘤的淋巴结的切除及病理学检查是一种重要的诊断评价，”FDA药品评价与研究中心医学影像产品的部门主任、医学博士、哲学博士 Marzella说。“使用Lymphoseek 时，医生将这款药物注射入肿瘤部位，然后使用手持放射性检测器，可发现已吸收Lymphoseek 放射性的前哨淋巴结。”
对于这种新的适应症，Lymphoseek的安全性及有效性在一项85名患有嘴唇、口腔和皮肤鳞状细胞癌患者参与的试验中得到验证。所有患者被注射入 Lymphoseek。外科医学随后切除病理检查疑似淋巴结（那些被Lymphoseek证实及那些基于肿瘤位置和手术实践的淋巴结）。结果显示，Lymphoseek指导的前哨淋巴结活组织检查可以确定癌症是否已通过淋巴系统发生扩散。
临床试验中最常见的副作用是疼痛或注射部位刺激。Lymphoseek由位于俄亥俄州都柏林的Navidea生物制药上市销售。
Lymphoseek Radiopharmaceutical Cleared in U.S. to Map Draining Lymph Nodes for Melanoma, Breast Cancer
Indications And Usage
Dosage And Administration
Table 1. Preparation of Lymphoseek for Administration Planned Number of Injections for a Patient Total Injection Volume Per Patient Reconstituted Vial Volume of Radiolabeled Lymphoseek
1 syringe x 0.1 mL 0.1 mL 0.5 mL
5 syringes x 0.1 mL or2 syringes x 0.25 mL or 1 syringe x 0.5 mL 0.5 mL 2.5 mL
5 syringes x 0.2 mL or4 syringes x 0.25 mL or 2 syringes x 0.5 mL 1 mL 5 mL
Dosage Forms And Strengths
The Kit for preparation of Lymphoseek (technetium Tc 99m tilmanocept) injection is supplied as five Tilmanocept Powder vials each containing 250 mcg tilmanocept and five DILUENT for Lymphoseek vials each containing 4.5 mL of sterile buffered saline. After radiolabeling with technetium Tc 99m, Lymphoseek contains approximately 92.5 MBq (2.5 mCi) and 250 mcg technetium Tc 99m tilmanocept in 0.5 mL to 5 mL total volume. Kit for preparation of Lymphoseek contains five Tilmanocept Powder vials each containing 250 mcg tilmanocept and five DILUENT for Lymphoseek vials containing 4.5 mL of sterile buffered saline. After radiolabeling with technetium Tc 99m and dilution, Lymphoseek contains approximately 92.5 MBq (2.5 mCi) and 250 mcg of technetium Tc 99m tilmanocept in 0.5 mL to 5 mL total volume for injection.
Contraindications
None. None.
Warning and Cautions
Hypersensitivity: Ask patients about prior reactions to drugs, especially dextran or modified forms of dextran. Observe for hypersensitivity signs and symptoms following Lymphoseek injection. Have resuscitation equipment and trained personnel immediately available. 5.1 Hypersensitivity Reactions Lymphoseek may pose a risk of hypersensitivity reactions due to its chemical similarity to dextran [see Description (11)]. Serious hypersensitivity reactions have been associated with dextran and modified forms of dextran (such as iron dextran drugs). Before administering Lymphoseek, ask patients about prior hypersensitivity reactions to drugs, especially to dextran and modified forms of dextran. Have resuscitation equipment and trained personnel immediately available at the time of Lymphoseek administration. 5.2 Radiation Risks Any radiation-emitting product may increase the risk for cancer, especially in pediatric patients. Adhere to the dose recommendations and ensure safe handling to minimize the risk for excessive radiation exposure to either patients or health care workers.
Adverse Reactions
The most common adverse reactions (incidence < 1%) are injection site irritation and/or pain. To report SUSPECTED ADVERSE REACTIONS, contact Navidea Biopharmaceuticals, Inc. at 1-800-476-5270 or www.lymphoseek.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In open label, single arm clinical trials, 553 patients with either breast cancer, malanoma, or squamous cell carcinoma of the oral cavity, skin, and lip received Lymphoseek. No patients experienced serious adverse reactions. Injection site irritation (4 patients; 0.7%) and pain (1 patient; 0.2%) were reported.
Use In Specific Populations
8.1 Pregnancy Pregnancy Category C There are no adequate or well-controlled studies of Lymphoseek in pregnant women. Additionally, animal reproduction studies have not been conducted with technetium Tc 99m tilmanocept. However, all radiopharmaceuticals, including Lymphoseek, have a potential to cause fetal harm. Lymphoseek should be given to a pregnant woman only if the potential benefit justifies the potential risk to the fetus. 8.3 Nursing Mothers It is not known whether technetium Tc 99m tilmanocept is present in human milk. Based on the half-life of technetium Tc 99m, a nursing woman should pump and discard milk for at least 60 hours (ten half-lives) after administration of Lymphoseek. 8.4 Pediatric Use Safety and effectiveness of Lymphoseek in patients less than 18 years of age have not been established. 8.5 Geriatric Use Of the 553 patients enrolled in clinical studies of breast cancer, melanoma, and squamous cell carcinoma (SCC) of oral cavity, skin, and lip, 179 (32%) were aged 65 or older. Review of the clinical data, including eva luation of the frequency of adverse reactions, has not identified differences in safety or efficacy between elderly patients (65 to 90 years of age) and younger patients (18 to 65 years of age).
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6681aa14-5ae3-4143-9d58-c2d92a143c03
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3f07d034-ecbb-42ff-a394-0f4a6c127c6e |
