Skov K A, Kumi C, Rootman J, Bussanich N, Fellenz M O
Br J Cancer. 1987 May;55(5):499-502. doi: 10.1038/bjc.1987.101.
Successful treatment of ocular tumours by chemotherapy and radiotherapy is sometimes limited by the special nature of the eye. Improvement is needed to avoid enucleation. Previous studies using locally administered antineoplastic agents have given promising results in the treatment of experimental ocular melanoma and spontaneous lymphoma. Another approach is use of radiosensitizers to improve radiotherapeutic effect. For the present study, 5-thio-D-glucose and cis-platin were chosen for evaluation in an ocular system because they exhibit antitumour activity, and interaction with radiation, particularly in hypoxia. Ocular absorption, toxicity, and pharmacokinetics after subconjunctival administration in rabbits were determined, and the effect of drug on tumours was measured using a Greene melanoma model. CHO cells were used for complimentary in vitro studies. 5-thio-D-glucose was readily absorbed into the eye (300 mg resulting in 5 mM in the aqueous) with no observable toxicity. When 5TG (300 mg) was administered at implantation, tumours were approximately half the size of controls. 5 mM 5TG is toxic to extremely hypoxic cells and gives measurable radiosensitization. Cis-platin levels as high as 0.68 microM were attained in the aqueous without local toxicity after 400 micrograms injection. This concentration causes toxicity in vitro. Cis-platin (400 mg) had a larger effect on tumour growth than 5TG given at, or one week after, implantation. Cis-platin may have potential for treatment of ocular tumours by local injection.
化疗和放疗对眼部肿瘤的成功治疗有时会受到眼睛特殊性质的限制。需要改进以避免眼球摘除。以往使用局部给药抗肿瘤药物的研究在治疗实验性眼黑色素瘤和自发性淋巴瘤方面取得了有前景的结果。另一种方法是使用放射增敏剂来提高放射治疗效果。在本研究中，选择5-硫代-D-葡萄糖和顺铂在眼部系统中进行评估，因为它们具有抗肿瘤活性，并且与辐射有相互作用，尤其是在缺氧情况下。测定了兔结膜下给药后的眼部吸收、毒性和药代动力学，并使用格林黑色素瘤模型测量了药物对肿瘤的影响。使用CHO细胞进行补充性体外研究。5-硫代-D-葡萄糖很容易被吸收到眼中（300毫克可使房水中达到5毫摩尔），且无明显毒性。在植入时给予5TG（300毫克），肿瘤大小约为对照组的一半。5毫摩尔的5TG对极度缺氧细胞有毒性，并能产生可测量的放射增敏作用。注射400微克后，房水中顺铂水平高达0.68微摩尔，且无局部毒性。该浓度在体外会产生毒性。顺铂（400毫克）对肿瘤生长的影响比植入时或植入一周后给予的5TG更大。顺铂通过局部注射可能具有治疗眼部肿瘤的潜力。
