卡鉑
卡鉑（Carboplatin）是獸醫腫瘤學中廣泛使用的第二代鉑類抗腫瘤藥物。主要用於治療多種癌和肉瘤，最常見的是作為截肢後**犬骨肉瘤**的輔助治療。 **臨床要點與優勢：** * **貓的安全性：** 與其前代藥物順鉑（Cisplatin，會導致貓發生致命性肺水腫）不同，卡鉑相對安全，常規用於貓科病患。 * **毒性較低：** 卡鉑通常被認為是「較溫和」的鉑類藥物。與順鉑相比，其腎毒性和致吐（嘔吐）可能性顯著較低，因此不需要在治療前後進行積極的靜脈輸液利尿。 * **多用途性：** 除了全身靜脈注射外，它在體腔內（胸腔積液）、動脈內和病灶內（馬類肉瘤、貓鼻平面癌）的應用也顯示出潛力。
作用機制: Carboplatin acts as a **bifunctional alkylating agent**. * **Cellular Entry & Activation:** Once inside the cell, the drug undergoes aquation (water molecules replace the cyclobutanedicarboxylate leaving group), forming highly reactive, positively charged platinum complexes. * **DNA Crosslinking:** These active complexes bind covalently to nucleophilic sites on DNA (primarily the N7 position of guanine and adenine). * **Inhibition:** This binding creates **intra-strand and inter-strand crosslinks** in the DNA double helix, physically obstructing DNA polymerases and RNA polymerases. * **Apoptosis:** The resulting DNA damage inhibits DNA replication, RNA transcription, and protein synthesis, ultimately triggering apoptosis (programmed cell death). > **Note:** Carboplatin is **cell-cycle nonspecific**, meaning it can damage cells during any phase of the cell cycle, though cells are most vulnerable during the G1 and S phases.
各物種劑量
- Antineoplastic · 300-350 mg/m2 · IV · every 3 weeks · Dosage may need adjustment in patients with reduced renal function.
- Neoplastic diseases (All uses) · 300 mg/m2 · IV · q3-4wk · As determined by oncology protocol · Injected into the side port of a freely running i.v. infusion of 0.9% NaCl over a 10-15 min period.
- Neoplastic diseases (Intrapleural/intraperitoneal) · 225-300 mg/m2 · Intrapleural/Intraperitoneal · As directed by specialist · As determined by oncology protocol · Diluted in 0.9% NaCl or 5% dextrose water over a 5-10 min period. Consult a veterinary oncology specialist before administering via this route.
- Adenocarcinoma · Intralesional use may be considered · Intralesional
- Antineoplastic · 180-260 mg/m2 · IV · every 3 weeks · Has also been administered intratumorally for nasal planum carcinomas.
- Neoplastic diseases (All uses) · 200 mg/m2 · IV · q3-4wk · As determined by oncology protocol · Injected into the side port of a freely running i.v. infusion of 0.9% NaCl over a 10-15 min period. Monitor for delayed/unpredictable side effects.
- Neoplastic diseases (Intrapleural/intraperitoneal) · 200-240 mg/m2 · Intrapleural/Intraperitoneal · As directed by specialist · As determined by oncology protocol · Diluted in 0.9% NaCl or 5% dextrose water over a 5-10 min period. Consult a veterinary oncology specialist before administering via this route.
給藥途徑
禁忌症
- History of hypersensitivity to carboplatin or other platinum agents
- Severe bone marrow depression
- Pregnancy (fetotoxic and embryotoxic - Category D)
不良反應
- Bone marrow suppression (neutropenia, thrombocytopenia)
- Anorexia
- Vomiting (typically 2-4 days post-dose)
- Hepatotoxicity (elevated bilirubin and liver enzymes)
- Nephrotoxicity (less frequent than cisplatin)
- Neuropathies (rare)
- Ototoxicity (rare)
- Anaphylactoid reactions (rare)
- Hyperuricemia
藥物相互作用
- Aminoglycosides · Potential for increased risk of nephrotoxicity or ototoxicity. · major
- Cisplatin · Patients previously treated with cisplatin have an increased risk of developing neurotoxicity or ototoxicity after receiving carboplatin.
- Myelosuppressive drugs · The leukopenic or thrombocytopenic effects secondary to carboplatin may be enhanced.
- Radiation therapy · Potential for increased hematologic toxicity.
- Vaccines · Live or killed virus vaccines administered after therapy may have reduced efficacy. Carboplatin may also potentiate live virus vaccine replication and increase adverse effects.
- Nephrotoxic agents (e.g., NSAIDs, Amphotericin B) · Increased risk of cumulative nephrotoxicity. · major
- Vaccines (live) · May adversely affect the safety and efficacy of vaccinations due to immunosuppression. · major
- Radiotherapy · Potential to act as a radiosensitizer for patients receiving concomitant radiotherapy. · moderate
監測
- CBC (Complete Blood Count) to monitor nadir
- Serum electrolytes
- Uric acid
- Baseline renal and hepatic function tests
過量
An overdose of carboplatin is expected to cause severe, aggravated effects associated with the drug's primary toxicities: **bone marrow suppression, nephrotoxicity, and hepatotoxicity**. * **Monitoring:** Closely monitor for neurotoxicity, ototoxicity, hepatotoxicity, and nephrotoxicity. * **Treatment:** Therapy is primarily supportive as no specific antidote is available. Plasmapheresis or hemodialysis could potentially be of benefit in rapidly removing the drug from systemic circulation.
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