Evaluation of response to chemotherapy in retinoblastoma heterotransplanted to the eyes of nude mice.
The role of chemotherapy in the treatment of retinoblastoma (RB) is unsatisfactory and clinical research is severely limited. A xenograft model for testing chemotherapeutic and other agents has been developed by the heterotransplantation of human RB cells into the anterior chamber of the nude mouse eye. A grading system for visually monitored tumor growth was designed to allow serial observations and documentation of the response to therapy in the model. This method of monitoring compared favorably with histopathologic, photographic, or other criteria in the reproducible, sequential evaluation of tumor status. Six chemotherapeutic agents [vincristine (VCR), doxorubicin (DOX), actinomycin D (ACT-D), dimethyltriazeno-imidazole carboxamide (DTIC), cyclophosphamide (CPM), and diaziquone (AZQ)] were then tested in the model against a patient-derived xenograft line. Results were expressed as the delay in tumor progression judged by serial grading. CPM produced a consistent response in all treated tumors, as did DTIC to a lesser, more variable extent. In 3 of 10 tumors treated with CPM and in 1 of 18 treated with DTIC, complete responses were maintained for at least 20 weeks. VCR, DOX, and ACT-D were ineffective, producing patterns of tumor progression no different from those in the control group. AZQ was most effective, producing responses far exceeding those of conventional agents. The model allows quantitative documentation of the response to therapy in heterotransplanted human RB. Further testing of new agents and combinations is warranted. AZQ may be active against RB.
White
L
L
Children's Leukaemia and Cancer Research Unit, Prince of Wales Children's Hospital, Wales, Sydney, Australia.
Szirth
B C
BC
Benedict
W F
WF
D000818:Animals; D001388:Aziridines / Q000627:therapeutic use; D016227:Benzoquinones; D003520:Cyclophosphamide / Q000627:therapeutic use; D005134:Eye Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012175:Retinoblastoma / Q000188:drug therapy* / Q000473:pathology; D014183:Transplantation, Heterologous
D001388:Aziridines; D016227:Benzoquinones; D003520:Cyclophosphamide; C029108:diaziquone