ロムスチン
ロムスチン（一般に**CCNU**として知られる）は、高脂溶性のニトロソウレア系アルキル化抗悪性腫瘍薬です。脂溶性が高いため血液脳関門を容易に通過し、中枢神経系（CNS）の悪性腫瘍の治療において独自の価値を持っています。 **主な獣医学的適応症：** * **肥満細胞腫（MCT）：** 犬および猫の第一選択薬またはレスキュー療法として頻繁に使用されます。 * **組織球肉腫：** 犬の局所性または播種性組織球肉腫の第一選択治療と見なされています。 * **リンパ腫：** 再発性多中心型リンパ腫のレスキュー薬として、または上皮向性（皮膚）リンパ腫の主要薬としてよく使用されます。 * **CNS腫瘍：** 原発性脳腫瘍（神経膠腫など）または転移性CNS病変に使用されます。 > **臨床のポイント：** ロムスチンは、犬において遅発性、蓄積性、および不可逆的な可能性のある肝毒性を引き起こすことで知られています。多くの獣医腫瘍医は、肝保護剤（SAMeやシリマリンなど）の併用を強く推奨しています。
作用機序: 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.
動物種別の用量
- 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.
用量は獣医療従事者向けの臨床リファレンスです。必ず最新の添付文書と個々の患者で確認してください。
投与経路
禁忌
- 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
有害事象
- 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)
薬物相互作用
- 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
モニタリング
- 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
過量投与
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 の薬剤リファレンスは、獣医療従事者向けの臨床意思決定支援を目的としており、専門的判断やメーカーの最新添付文書に代わるものではありません。