ビンクリスチン
ビンクリスチンは、ニチニチソウ（*Catharanthus roseus*）由来の細胞周期特異的（M期）抗悪性腫瘍薬です。獣医腫瘍学における重要な薬剤であり、主にリンパ腫などのリンパ系および造血系腫瘍に対する多剤併用化学療法（CHOP療法など）で使用されます。 主な臨床的特徴： * **骨髄抑制が軽度**：他の多くの抗がん剤（類似薬のビンブラスチンなど）とは異なり、標準用量では骨髄抑制が軽度であるため、併用療法において非常に有用です。 * **可移植性性器腫瘍（TVT）**：犬のTVTに対しては単剤で極めて高い有効性を示します。 * **免疫介在性血小板減少症（IMT）**：難治性のIMTの治療にも独自に使用されます。巨核球の断片化を促進し、血小板の血中への放出を早めます。 * **壊死性物質（起泡薬）**：重度の組織障害を引き起こす起泡薬です。壊滅的な血管外漏出による損傷を防ぐため、適切に留置されたカテーテルからの厳密な静脈内投与が必須です。
作用機序: Vincristine is a cell-cycle specific agent that acts during the **M-phase** (mitosis). * **Antineoplastic Action**: It binds specifically to **tubulin** dimers → inhibits microtubule polymerization → prevents the formation of the mitotic spindle → arrests cell division in **metaphase**, ultimately leading to apoptosis. * **Metabolic Effects**: It interferes with amino acid metabolism by inhibiting glutamic acid utilization and preventing purine synthesis, citric acid cycle, and urea formation. * **Thrombocytosis**: The exact mechanism is unknown, but it is believed to stimulate megakaryocyte fragmentation, accelerating the release of platelets into the peripheral blood. * **Immunosuppression**: Exhibits mild immunosuppressive activity, which may contribute to its efficacy in immune-mediated conditions.
動物種別の用量
- Neoplastic diseases · 0.5-0.75 mg/m2 · IV · every 1-3 weeks · Dosed in mg/m2, NOT mg/kg. Consultation with an oncologist recommended.
- Neoplastic diseases (particularly lymphoproliferative disorders) · See Appendix for chemotherapy protocols and conversion of body weight to body surface area. · IV · Not specified · Not specified · Must be administered i.v. through a carefully pre-placed catheter.
- Neoplastic diseases · 0.5 mg/m2 (usually 2.5-3 mg total dose per horse) · IV · weekly · Often used in CAP protocol with cytarabine and cyclophosphamide.
- Neoplastic diseases (usually in combination protocols) · 0.5-0.75 mg/m2 · IV · every 1-2 weeks · Dosed in mg/m2, NOT mg/kg. Consultation with an oncologist recommended.
- Transmissible venereal tumor (TVT) · 0.5 mg/m2 (maximum dose 1 mg) · IV · once weekly · for 4-6 weeks · Used as sole therapy.
- Adjunctive treatment of immune-mediated thrombocytopenia (IMT) · 0.5 mg/m2 · IV · once · If platelet count <10-20,000 cells/mcL or bleeding; consider bone marrow aspiration to document megakaryocytes.
- Adjunctive treatment of immune-mediated thrombocytopenia (IMT) refractory to prednisone · 0.5-0.7 mg/m2 · IV · once · Given as an IV bolus or as an infusion over 4-6 hours.
- Adjunctive treatment of immune-mediated thrombocytopenia (IMT) · 0.02 mg/kg · IV · once · Generally single use.
投与経路
禁忌
- Preexisting neuromuscular disease
- Severe leukopenia
- Uncontrolled infection
- No specific absolute contraindications listed, but requires extreme caution in specific disease states
有害事象
- Peripheral neuropathy (proprioceptive deficits, spinal hyporeflexia)
- Paralytic ileus and severe constipation
- Mild leukopenia
- Tissue necrosis and sloughing (if extravasated)
- Anorexia, vomiting, diarrhea
- Impaired platelet aggregation
- Increased liver enzymes
- Syndrome of inappropriate ADH secretion (SIADH)
- Jaw pain
- Alopecia
- Stomatitis
- Seizures
- Pulmonary edema (rare, reported in cats)
- Peripheral neuropathy
- Ileus
- GI tract toxicity
薬物相互作用
- Asparaginase · Additive neurotoxicity may occur; less common if asparaginase is administered after vincristine.
- Mitomycin · Severe bronchospasm has occurred in humans receiving mitomycin-C with Vinca alkaloids.
- Amiodarone · Inhibits P-glycoprotein; may increase vincristine toxicity, especially in MDR1/ABCB1 mutant dogs.
- Azole Antifungals (e.g., ketoconazole) · Inhibits P-glycoprotein; may increase vincristine toxicity.
- Carvedilol · Inhibits P-glycoprotein; may increase vincristine toxicity.
- Cyclosporine · Inhibits P-glycoprotein; may increase vincristine toxicity.
- Diltiazem · Inhibits P-glycoprotein; may increase vincristine toxicity.
- Erythromycin · Inhibits P-glycoprotein; may increase vincristine toxicity.
- Clarithromycin · Inhibits P-glycoprotein; may increase vincristine toxicity.
- Quinidine · Inhibits P-glycoprotein; may increase vincristine toxicity.
- Spironolactone · Inhibits P-glycoprotein; may increase vincristine toxicity.
- Tamoxifen · Inhibits P-glycoprotein; may increase vincristine toxicity.
- Verapamil · Inhibits P-glycoprotein; may increase vincristine toxicity.
モニタリング
- Efficacy (tumor burden reduction or platelet count)
- Peripheral neuropathic clinical signs (e.g., gait abnormalities, constipation)
- Complete blood counts (CBC) with platelets
- Liver function tests (prior to therapy and repeated as necessary)
- Serum uric acid
- Complete Blood Count (CBC) prior to each dose
- IV catheter site for any signs of extravasation during administration
- Gastrointestinal signs (monitoring for ileus or severe constipation)
- Neurological exams (monitoring for peripheral neuropathy, e.g., dragging paws, loss of reflexes)
過量投与
Vincristine has a narrow therapeutic index. * **Dogs**: The maximally tolerated dose is reported as 0.06 mg/kg every 7 days for 6 weeks. Toxicity signs include slight anemia, leukopenia, increased liver enzymes, and neuronal shrinkage in the peripheral and central nervous systems. * **Cats**: The lethal dose is reportedly 0.1 mg/kg. Toxic signs include weight loss, seizures, leukopenia, and general debilitation. A reported 10X overdose (5 mg/m2) resulted in death within 72 hours despite intensive care (including calcium folinate). * **Treatment**: Primarily supportive. Includes cardiovascular and hematologic monitoring, anticonvulsants for seizures, and prevention of ileus. Fluid restriction and loop diuretics may be needed to manage SIADH. Leucovorin calcium has been used in humans, but efficacy is unconfirmed.
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