多柔比星 / 阿黴素
**多柔比星 (Doxorubicin)** 是一種蒽環類抗生素，也是小動物獸醫腫瘤學中最廣泛使用的抗腫瘤藥物之一。由於其鮮紅的顏色和強烈的副作用，常被俗稱為「小紅莓 (Red Devil)」。它可作為單一藥物或在多藥物聯合化療方案中使用。 * **廣效性**：對犬貓的多種惡性腫瘤高度有效，包括**淋巴瘤、癌、白血病和肉瘤**。 * **來源**：最初從 *Streptomyces peucetius* 中分離出來。 * **臨床要點**：雖然具有抗菌特性，但其強烈的細胞毒性使其完全無法作為抗感染藥物使用。它是一種強烈的**發泡劑 (vesicant)**；必須極度小心確保靜脈通路暢通，以防止嚴重的血管外滲漏損傷。
作用機制: Doxorubicin is a cell-cycle non-specific cytotoxic agent with multiple mechanisms of action: * **Topoisomerase II Inhibition**: Intercalates between DNA base pairs and inhibits **topoisomerase II** → prevents DNA resealing → causes double-strand DNA breaks → triggers apoptosis. * **Macromolecular Synthesis Inhibition**: Directly inhibits DNA synthesis, DNA-dependent RNA synthesis, and protein synthesis. * **Free Radical Generation**: Undergoes electron reduction to form anthracycline semiquinone free radicals (often iron-mediated) → causes severe oxidative stress and lipid peroxidation. * **Clinical Pearl**: The heart is particularly susceptible to doxorubicin-induced oxidative damage because cardiac tissue has inherently low levels of **catalase**, an enzyme necessary to neutralize hydrogen peroxide. This is the primary mechanism behind its cumulative cardiotoxicity.
各物種劑量
- Antineoplastic · 30 mg/m2 IV every 2-3 weeks · IV · every 2-3 weeks · Depending on the protocol used. Maximum cumulative dose = 240 mg/m2.
- Lymphoma, sarcomas, carcinomas · 30 mg/m2 (Use 1 mg/kg in dogs weighing <10 kg) · IV · q3wk · Maximum total cumulative dose not to exceed 240 mg/m2 · Administer over a minimum of 10 minutes into side port of freely running 0.9% NaCl.
- Antineoplastic · 20-30 mg/m2 IV every 2-4 weeks · IV · every 2-4 weeks · Depending on the protocol used. Maximum cumulative dose is usually 240 mg/m2.
- Lymphoma, soft tissue sarcomas · 1 mg/kg or 20-25 mg/m2 · IV · q3-5wk · Maximum total cumulative dose not to exceed 240 mg/m2 · Nephrotoxicity is a major risk in cats, especially at cumulative dosages >100 mg/m2.
- Antineoplastic · 30 mg/m2 IV every 3 weeks · IV · every 3 weeks · Depending on the protocol used.
劑量為合格獸醫專業人員的臨床參考。請務必對照最新藥品仿單及個別病患確認。
給藥途徑
禁忌症
- Pre-existing severe myelosuppression
- Impaired cardiac function
- Patients who have reached the total cumulative dose limit of doxorubicin and/or daunorubicin
- Cats with pre-existing renal insufficiency
不良反應
- Bone marrow suppression (nadir 5-10 days)
- Cardiac toxicity (acute arrhythmias and cumulative cardiomyopathy)
- Nephrotoxicity (particularly in cats)
- Gastroenteritis (anorexia, vomiting, diarrhea)
- Alopecia
- Stomatitis
- Immediate hypersensitivity/anaphylaxis (primarily in dogs)
- Severe tissue ulceration and necrosis (if extravasated)
藥物相互作用
- Antineoplastic agents, other · May potentiate the toxic effects of doxorubicin
- Calcium-channel blockers · Potentially could increase risk for cardiotoxicity associated with doxorubicin
- Carbamazepine · Decreased carbamazepine levels
- Cisplatin · Increased risk of toxicity for both agents; carefully weigh risks versus benefits
- Cyclophosphamide · May increase doxorubicin blood levels (AUC); doxorubicin may potentiate and prolong hematologic toxicity; coma and seizures have been reported in human patients · major
- Cyclosporine · Can increase doxorubicin and doxorubicinol (active metabolite) levels
- Glucosamine · May reduce doxorubicin effectiveness; use together not recommended in humans
- Phenytoin · Doxorubicin may decrease phenytoin levels
- Phenobarbital · May increase elimination and reduce blood levels of doxorubicin
- Streptozocin · May inhibit doxorubicin metabolism
- Verapamil · May increase doxorubicin levels
- Warfarin · Increased risk for bleeding
- Zidovudine · Increased risk for neutropenia
監測
- Efficacy of tumor response
- CBC with platelets (monitor for myelosuppression, nadir at 5-10 days)
- ECG and/or echocardiogram (especially in dogs with pre-existing heart disease or predisposed breeds)
- Hepatic function prior to and during therapy
- Urinalysis, serum creatinine, and BUN (especially in cats due to nephrotoxicity risk)
過量
Inadvertent acute overdosage may be manifested by severe exacerbations of adverse effects (profound myelosuppression, severe GI toxicity, acute cardiotoxicity). A lethal dose for dogs has been reported as 72 mg/m2. **Treatment**: Supportive and symptomatic therapy is required. **Dexrazoxane** may be useful to help prevent cardiac toxicity and should be considered in cases of massive overdose.
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