トセラニブ
トセラニブは、獣医療専用に開発された経口分子標的薬であり、小分子チロシンキナーゼ阻害薬（TKI）に分類されます。 **主な適応症:** * 犬のグレードIIまたはIIIの再発性皮膚**肥満細胞腫（MCT）**（所属リンパ節病変の有無を問わない）の治療薬としてFDAに承認されています。 **適応外 / 研究中の用途:** * 肉腫、癌腫、黒色腫、多発性骨髄腫など、犬の様々な腫瘍の治療に有用である可能性があります。 * 腫瘍の血管新生と増殖を抑制するための**メトロノミック化学療法**（低用量の抗がん剤を持続的に投与する療法）の一部として利用されることが増えています。
作用機序: Toceranib competitively inhibits **ATP** binding at the intracellular kinase domain of several split kinase receptor tyrosine kinases (RTKs). **Key Targets:** * **VEGFR-2** (Vascular Endothelial Growth Factor Receptor-2) * **PDGFR-β** (Platelet-Derived Growth Factor Receptor-Beta) * **c-Kit** (Stem Cell Growth Factor Receptor) **Pathway:** Inhibition of RTKs → prevents receptor phosphorylation → blocks downstream signal transduction → exerts an antiproliferative effect on endothelial cells and induces cell cycle arrest and apoptosis in tumor cells. Because canine mast cell tumor growth is frequently driven by activating mutations in **c-Kit**, toceranib directly targets the neoplastic cells while simultaneously reducing tumor angiogenesis via **VEGFR-2** and **PDGFR-β** inhibition.
動物種別の用量
- Malignancies (Off-label) · 2.5 mg/kg (range 1.5-3.25 mg/kg) · PO · Monday, Wednesday, Friday basis (or less frequently q48h) · Ongoing based on response and toxicity · Limited information available. Off-label use.
- Patnaik grade II or III, recurrent, cutaneous mast cell tumors (Label Dose) · 3.25 mg/kg PO every other day (q48h) · PO · q48h · Ongoing as tolerated · Dose reductions of 0.5 mg/kg (to a minimum dose of 2.2 mg/kg every other day) and dose interruptions for up to two weeks may be utilized to manage adverse reactions. Do not split tablets.
- Patnaik grade II or III, recurrent, cutaneous mast cell tumors (Clinical Experience Dose) · 2.5-2.75 mg/kg PO every other day · PO · q48h · Ongoing as tolerated · Often better tolerated than the label dose, resulting in less toxicity and fewer drug holidays. Alternatively, a Monday/Wednesday/Friday schedule may be used, especially when combined with other drugs in metronomic protocols.
- Mast cell tumours and other malignancies · 2.5-3.25 mg/kg · PO · q48h or on a Monday, Wednesday, Friday basis · Ongoing based on response and toxicity · Monitor closely. See Appendix for specific chemotherapy protocols.
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
- Breeding, pregnant, or lactating bitches
- Dogs less than 24 months of age or weighing less than 5 kg (safe use not evaluated)
- Pregnant or lactating bitches
- Dogs < 2 years old
- Dogs < 5 kg
- Patients with any signs of gastrointestinal haemorrhage
- Known hypersensitivity to toceranib
有害事象
- Diarrhea (can be severe)
- Decreased or loss of appetite
- Lameness
- Weight loss
- Gastrointestinal bleeding (blood in stool, melena)
- Muscle cramping
- Neutropenia
- Hypoalbuminemia
- Thromboembolic disease (including pulmonary emboli)
- Vasculitis
- Pancreatitis
- Nasal depigmentation
- Change in coat or skin color
- Epistaxis
- Seizures
- Pruritus
- Diarrhoea
薬物相互作用
- NSAIDs (e.g., piroxicam, carprofen) · Increased risk of gastrointestinal ulceration or perforation. Use with extreme caution; never give on the same day as toceranib to avoid exacerbating GI toxicity.
- CYP3A4 Inhibitors (e.g., ketoconazole, fluconazole, itraconazole, clarithromycin, verapamil, grapefruit juice) · May theoretically increase toceranib plasma concentrations and toxicity. Use with caution.
- Corticosteroids · Increased risk of severe gastrointestinal toxicity and ulceration. · major
- NSAIDs · Increased risk of severe gastrointestinal toxicity and ulceration. · major
- Other chemotherapeutic agents · Potential for additive myelosuppression and systemic toxicity. Use with caution. · moderate
モニタリング
- CBC (monitor for neutropenia and anemia)
- Hematocrit
- Serum Albumin
- Creatinine
- Serum Phosphate
- Urinalysis
- Full chemistry panels
- Clinical signs of GI toxicity (diarrhea, fresh blood in stool, melena)
- Tumor size and response to therapy
- Blood pressure (baseline and monthly)
- Urinalysis (baseline and monthly, monitor for proteinuria)
- Haematology (baseline and monthly)
- Biochemistry (baseline and monthly, monitor albumin and ALT)
- Coagulation profiles (if adverse signs occur)
- Faecal occult blood tests (if adverse signs occur)
- Weekly owner check-ins for the first 6 weeks to monitor for GI signs
過量投与
Toceranib has a **narrow margin of safety**. While specific acute toxicity data is limited, overdoses are likely to cause severe gastrointestinal distress, myelosuppression, and vascular events. > **Action:** In the event of an acute overdose, consider immediate gut decontamination (emesis/activated charcoal) if caught early. Contact an animal poison control center for further guidance and provide aggressive supportive care.
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。