Shikani A H, Eisele D W, Domb A J
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Md.
Arch Otolaryngol Head Neck Surg. 1994 Nov;120(11):1242-7. doi: 10.1001/archotol.1994.01880350050009.
The role of chemotherapy for the treatment of squamous cell carcinoma of the head and neck is limited by the systemic toxicity of chemotherapeutic agents. An attractive alternative is the controlled and sustained release of anticancer agents from a resorbable polymer delivery system that is implanted next to the tumor. The advantages are a high locoregional drug concentration with low systemic levels and a delivery system that is not limited by poor blood supply caused by previous radiation therapy or surgery.
METHODS/SUBJECTS: The polymer used in this study was a biodegradable polyanhydride made up of fatty acid dimer and sebacic acid, Poly (FAD-SA), loaded with cisplatin. The tumor animal model was the nude mouse carrying human floor of mouth squamous cell carcinoma xenografts. Polymer-cisplatin pharmacokinetics and the effect of polymer delivery of cisplatin (5% and 7% drug/polymer at a weight/weight load) on tumor growth rates were evaluated.
Thirty-five days after implantation of the polymer, the mean treated tumor size was 65.5% of controls in the 5% group and 31.8% in the 7% group. Seventy days after implantation, the mean treated tumor size was 41.4% of controls in the 5% group and 38.1% in the 7% group, indicating a statistically significant delay of tumor growth compared with controls or with intraperitoneally injected cisplatin.
This study demonstrates that continuous release of cisplatin directly at the tumor site, using an implantable polymer, is effective against human head and neck squamous cell carcinoma xenografts in nude mice.
化疗药物的全身毒性限制了化疗在头颈部鳞状细胞癌治疗中的作用。一种有吸引力的替代方法是将抗癌药物从可吸收的聚合物给药系统中进行可控和持续释放，该系统植入肿瘤旁。其优点是局部药物浓度高而全身水平低，且给药系统不受先前放疗或手术导致的血供不良的限制。
方法/研究对象：本研究中使用的聚合物是由脂肪酸二聚体和癸二酸制成的可生物降解聚酸酐，聚（脂肪酸二聚体-癸二酸）（Poly (FAD-SA)），负载顺铂。肿瘤动物模型是携带人舌底鳞状细胞癌异种移植物的裸鼠。评估了聚合物-顺铂的药代动力学以及顺铂聚合物给药（重量/重量负载下药物/聚合物分别为5%和7%）对肿瘤生长速率的影响。
聚合物植入35天后，5%组治疗后的肿瘤平均大小为对照组的65.5%，7%组为31.8%。植入70天后，5%组治疗后的肿瘤平均大小为对照组的41.4%，7%组为38.1%，表明与对照组或腹腔注射顺铂相比，肿瘤生长有统计学意义的延迟。
本研究表明，使用可植入聚合物在肿瘤部位直接持续释放顺铂，对裸鼠体内的人源头颈部鳞状细胞癌异种移植物有效。
