Response of an ocular melanoma to subconjunctival injection of 5-thio-D-glucose or cis-platin.
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.
D000042:Absorption; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005134:Eye Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D010101:Oxygen Consumption; D011817:Rabbits; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D013997:Time Factors
D011838:Radiation-Sensitizing Agents; C003002:5-thio-D-glucose; D005947:Glucose; D002945:Cisplatin