洛莫司汀
洛莫司汀（通常稱為 **CCNU**）是一種高脂溶性的亞硝基脲類烷化抗腫瘤藥物。由於其高脂溶性，它能輕易穿透血腦屏障，這使其在治療中樞神經系統 (CNS) 惡性腫瘤方面具有獨特的價值。 **主要獸醫適應症：** * **肥大細胞瘤 (MCTs)：** 常作為犬貓的一線或救援療法。 * **組織細胞肉瘤：** 被認為是犬局部或播散性組織細胞肉瘤的首選治療方法。 * **淋巴瘤：** 常作為復發性多中心型淋巴瘤的救援藥物，或作為上皮性（皮膚）淋巴瘤的主要藥物。 * **中樞神經系統腫瘤：** 用於原發性腦腫瘤（如神經膠質瘤）或轉移性中樞神經系統病變。 > **臨床要點：** 洛莫司汀以在犬隻身上引起延遲性、累積性且可能不可逆的肝毒性而聞名。許多獸醫腫瘤學家強烈建議同時給予保肝藥物（如 SAMe 和水飛薊素）。
作用機制: Lomustine is a **cell cycle-phase nonspecific** antineoplastic drug, meaning it is toxic to cancer cells regardless of their current phase in the division cycle. * **Alkylating Activity:** It undergoes spontaneous decomposition in vivo to form reactive intermediates. These intermediates transfer alkyl groups to DNA and RNA → causing **cross-linking of DNA strands** → preventing DNA replication and RNA transcription. * **Carbamoylation:** The drug also causes carbamoylation of cellular proteins (specifically lysine residues) → **inhibits DNA repair enzymes**, preventing the cancer cell from fixing the alkylation damage, ultimately leading to apoptosis.
各物種劑量
- Antineoplastic (CNS neoplasms, lymphomas, mast cell tumors) · 60 mg/m2 · PO · every 6 weeks
- Antineoplastic (CNS neoplasms, lymphomas, mast cell tumors) · 10 mg · PO · every 3 weeks · Administered as a single 10 mg total dose.
- All uses · 30-60 mg/m2 · PO · q4-6wk · As directed by oncologist · Dose is suggested but not well established. Specialist advice should be sought, as dosing intervals may need to be increased due to delayed myelosuppression.
- Antineoplastic (CNS neoplasms, lymphomas, mast cell tumors, histiocytic sarcomas) · 50-90 mg/m2 · PO · every 2-6 weeks · Dosed in mg/m2, NOT mg/kg. Exact protocol depends on indication.
- All uses (brain tumours, mast cell tumours, lymphoma, histiocytic sarcoma) · 60-80 mg/m2 · PO · q3-4wk · As directed by oncologist · S-Adenosylmethionine and silybin may be used to prevent or treat hepatotoxicity.
劑量為持牌獸醫專業人員的臨床參考。請務必對照最新藥品說明書及個別病患確認。
給藥途徑
禁忌症
- Pre-existing severe bone marrow depression
- Active infections
- Pregnancy (Teratogenic - FDA Category D)
- Nursing/lactating animals
- Pre-existing bone marrow suppression
- Pre-existing liver disease
- Pregnancy and lactation
不良反應
- Bone marrow depression (anemia, thrombocytopenia, leukopenia) - nadirs typically at 1-6 weeks
- Hepatotoxicity (delayed, cumulative, chronic, and irreversible in dogs)
- Anorexia
- Vomiting
- Diarrhea
- Stomatitis
- Alopecia
- Corneal de-epithelization
- Renal toxicity (rare)
- Pulmonary infiltrates or fibrosis (rare)
- Myelosuppression (dose-limiting; severe neutropenia and thrombocytopenia)
- Hepatotoxicity (cumulative, dose-related, potentially irreversible in dogs)
- Gastrointestinal toxicity (vomiting, diarrhea, anorexia)
藥物相互作用
- Immunosuppressive drugs (e.g., azathioprine, cyclophosphamide, corticosteroids) · May increase the risk of severe infection due to additive immunosuppression.
- Myelosuppressive drugs (e.g., chloramphenicol, flucytosine, amphotericin B, colchicine) · Additive bone marrow depression; concurrent use should be avoided or strictly monitored.
- Live virus vaccines · Increased risk of vaccine-induced infection or decreased vaccine efficacy; use with extreme caution or avoid during therapy.
- Other myelosuppressive agents · Increased risk of severe and potentially fatal bone marrow suppression. · major
- Phenobarbital (and other liver enzyme inducers) · Altered metabolism of lomustine, which requires hepatic microsomal enzyme hydroxylation. Use with caution. · moderate
- Cimetidine · Enhances the toxicity of lomustine (reported in humans). · major
監測
- CBC with platelets one week after dosing and prior to next dose (If platelets < 200,000/mcl, stop therapy until thrombocytopenia is resolved)
- Liver function tests (ALT, AST, ALP, Bilirubin) initially before starting treatment and then every 3-4 months
- Complete Blood Count (CBC) including platelets, particularly 7-14 days post-administration (and up to 6 weeks in cats)
- Liver function tests (ALT, AST, ALP, Bilirubin) prior to every dose
- Clinical signs of gastrointestinal toxicity
過量
Because of the severe potential toxicity of the drug (profound myelosuppression and hepatotoxicity), overdoses should be treated aggressively. * Employ **gut emptying protocols** (emesis, activated charcoal) immediately if exposure was recent and the patient is asymptomatic. * Provide aggressive supportive care and monitor CBC and liver enzymes closely. * Consult an animal poison control center or a veterinary oncologist for specific guidance.
VetSheet 藥物參考供持牌獸醫專業人員作臨床決策輔助之用,不能取代專業判斷或廠方最新藥品說明書。