The chemosensitivity profile of retinoblastoma.
Retinoblastoma is a rare malignant tumour of the developing retina with an incidence of 1 in 20,000 live births in all human races. Chemotherapy is used in retinoblastoma as adjuvant therapy to prevent the growth of metastases and to treat metastatic disease once this has become clinically apparent. Current regimens are based on empirical drug combinations, and few clinical trials have been conducted because of the rarity of this tumour. Chemosensitivity testing offers a way of testing a large number of agents against tumours. The ATP-based chemosensitivity assay (ATP-TCA) has already helped to design new regimens for melanoma and breast and ovarian cancer. Primary retinoblastoma tumour material was obtained from 10 eyes, 7 of which contained sufficient viable cells for ATP-TCA. The results show very high sensitivity to single agents, particularly cisplatin, doxorubicin and vinca aLkaloids. Of the anti-metabolites tested, 5-FU is relatively disappointing (although still active), and gemcitabine shows considerable activity consistent with a cytotoxic effect. The shape of the inhibition curves is interesting. There is a plateau effect with the topoisomerase inhibitors and vinblastine, which is not present with the cisplatin. One tumour was much more resistant than the others tested, particularly to vinblastine but also to the topoisomerase inhibitors, which failed to achieve complete kill at any concentration tested, consistent with a multidrug resistance phenotype. Of the combinations (VAC and VEC), the VAC regimen looks marginally more active in the more resistant of the two cases tested to date. These data confirm that retinoblastoma is a rapidly growing malignancy that is very susceptible to cytotoxic drugs of all types. Chemosensitivity testing provides a practical method of testing new regimens before clinical trials in retinoblastoma patients.
Di Nicolantonio
Federica
F
Translational Oncology Research Centre, Department of Histopathology, Queen Alexandra Hospital, Portsmouth, PO6 3LY, UK.
Neale
Michael
M
Onadim
Zerrin
Z
Hungerford
John L
JL
Kingston
Judith L
JL
Cree
Ian A
IA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D019572:Retinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012175:Retinoblastoma / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D000255:Adenosine Triphosphate