米托蒽醌
米托蒽醌（Mitoxantrone）是一種合成的蒽醌類（anthracenedione）抗腫瘤藥物，在獸醫腫瘤學中用於治療犬貓的多種惡性腫瘤。 **主要臨床應用：** * **淋巴瘤：** 常在第一線化療方案（如CHOP）失效時作為救援藥物。 * **癌（Carcinomas）：** 對移行細胞癌（TCC）、鱗狀細胞癌、腎腺癌和甲狀腺癌有效。 * **肉瘤（Sarcomas）：** 用於纖維肉瘤、血管外皮細胞瘤和乳腺腺癌。 **臨床要點：** * 結構上與蒽環類藥物（如阿黴素 doxorubicin）相似，但缺乏氨基糖基團，這大幅減少了自由基的產生，因此其**心臟毒性遠低於阿黴素**。 * 由於其腎臟清除率極低（約10%），對於患有腎功能不全的貓來說，是比阿黴素更安全的替代選擇。 * 由於其深藍色外觀及強效作用，在獸醫腫瘤學中常被俗稱為「藍色閃電（blue thunder）」。
作用機制: Mitoxantrone exerts its cytotoxic effects through multiple mechanisms: * **DNA Intercalation:** It inserts itself between DNA base pairs, causing structural distortion. * **Electrostatic Interaction:** Nonintercalative binding to DNA further stabilizes the drug-DNA complex. * **Topoisomerase II Inhibition:** **(Pharmacological addition)** It inhibits the enzyme Topoisomerase II, preventing the religation of DNA strands and leading to double-strand DNA breaks. * **Synthesis Inhibition:** Ultimately inhibits both DNA and RNA synthesis. While it is not strictly cell-cycle phase specific, it demonstrates the highest activity during the **S phase** (DNA synthesis phase) of the cell cycle.
各物種劑量
- Soft-tissue sarcomas · 6-6.5 mg/m2 IV given every 3-4 weeks for 4-6 treatments · IV · every 3-4 weeks · 4-6 treatments
- Effective dose (general) · 6.5 mg/m2 IV every 2-3 weeks · IV · every 2-3 weeks
- Single rescue agent for lymphoma · 6-6.5 mg/m2 IV every 3 weeks · IV · every 3 weeks
- Transitional cell carcinoma · 5 mg/m2 IV every 21 days with piroxicam (0.3 mg/kg PO once daily) · IV · every 21 days
- Lymphoma, squamous cell carcinoma, transitional cell carcinoma, mammary gland tumors, etc. · 6 mg/m2 IV every 2-3 weeks · IV · every 2-3 weeks
- Single rescue agent for lymphoma · 5.5-6 mg/m2 IV every 3 weeks · IV · every 3 weeks
- Rescue agent for canine lymphoma · 6 mg/m2 IV every 2-3 weeks · IV · every 2-3 weeks · Check CBC on day 7 after treatment and the protocol can be repeated on day 14 or 21 if the dog attains complete or partial response. Combining with DTIC (dacarbazine) may improve response rate.
- Transitional cell carcinoma after laser ablation of the primary tumor · 5 mg/m2 IV every 3 weeks for 4 treatments · IV · every 3 weeks · 4 treatments · Piroxicam was given at a dosage of 0.3 mg/kg PO once daily for the remaining life of the dog.
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
- Severe pre-existing myelosuppression
- Concurrent active infection
- Significantly impaired cardiac function
- Patients with prior extensive cytotoxic drug or radiation exposure (relative)
- Pregnancy (FDA Category D) and nursing mothers
- Pre-existing myelosuppression
- Concurrent infection
- Hepatic disease
- Impaired cardiac function
不良反應
- Dose-dependent GI distress (vomiting, anorexia, diarrhea)
- Bone marrow depression (neutropenia, sepsis; nadir typically around day 10)
- Non-regenerative anemia
- Lethargy
- Seizures (specifically noted in cats)
- Blue-green discoloration of urine and sclera (benign)
- Tissue necrosis or phlebitis (if extravasated, though less severe than doxorubicin)
- Rarely: conjunctivitis, jaundice, renal failure, allergic reactions, thrombocytopenia
- Gastrointestinal signs (vomiting, anorexia, diarrhoea)
- Bone marrow depression (WBC nadir generally at 10 days)
- Seizure activity (reported in cats)
- Blue discoloration of urine and sclera (very rare)
- Acute renal failure (anecdotal in cats)
藥物相互作用
- Doxorubicin, Daunorubicin, or Radiation Therapy · Cardiotoxicity risks may be enhanced in patients that have previously received these therapies to the mediastinum.
- Immunosuppressant Drugs (e.g., azathioprine, cyclophosphamide, corticosteroids) · Concurrent use may significantly increase the risk of severe infection.
- Myelosuppressive Drugs (e.g., chloramphenicol, flucytosine, amphotericin B, colchicine) · Additive bone marrow depression; use with extreme caution.
- Live Vaccines · Increased risk of vaccine-induced infection; should be used with extreme caution or avoided during therapy.
- Myelosuppressive agents · Increased risk of severe bone marrow depression · major
- Immunosuppressive agents · Increased risk of severe immunosuppression and infection · major
- Heparin · Chemically incompatible · major
監測
- CBC with differential and platelets (especially around day 7-10 to check for nadir)
- Tumor measurements/efficacy
- Chest radiographs, ECG, or other cardiac function tests (if cardiac symptomatology is present)
- Liver function tests (if jaundice or clinical signs of hepatotoxicity occur)
- Serum uric acid levels (for susceptible patients)
- Complete Blood Count (CBC), especially WBC count around day 10 post-administration
- Gastrointestinal signs (vomiting, diarrhoea, appetite)
- Renal parameters (especially in cats)
- Hepatic function
- Cardiac function (echocardiogram) if pre-existing disease exists
過量
Due to the narrow therapeutic index and potential for serious toxicity (profound myelosuppression, severe GI mucosal damage, sepsis), dosage determinations must be made with extreme care. Overdose management is primarily supportive, focusing on aggressive fluid therapy, broad-spectrum antibiotics to manage sepsis secondary to neutropenia, and potentially the use of recombinant granulocyte-colony stimulating factors (G-CSF) to accelerate bone marrow recovery.
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。