Sequence-dependent effects of ZD1839 ('Iressa') in combination with cytotoxic treatment in human head and neck cancer.
Bottom Line: The results indicated that ZD1839 applied before radiation gave the best effects (P=0.002); an effect that was strongest in those p53-mutated cell lines that express the highest epidermal growth factor receptor levels.The effects of ZD1839 with cisplatin and/or 5-fluorouracil were sequence dependent (P<0.003), with the best results achieved when ZD1839 was applied first.For the triple combinations, ZD1839 applied before cisplatin and 5-fluorouracil resulted in a slight synergistic effect (P=0.03), although the effect was greater when ZD1839 was applied both before and during cytotoxic drug exposure.
Affiliation: Department of Oncopharmacology, Oncopharmacology Unit, Centre Antoine Lacassagne, 33 Avenue de Valombrose, 06189 Nice Cedex 2, France.Show MeSH
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Mentions: Dose-effect curves for the different ZD1839/radiation exposure combinations for CAL33 cells: (A) sequence I, (B) sequence II, (C) sequence III. For each combination sequence of ZD1839 and radiation, the dose-effect curve of the combination was compared with the dose-effect curves of ZD1839 alone and radiation alone. Radiation dose ranged from 0.5 to 10 Gy.
Affiliation: Department of Oncopharmacology, Oncopharmacology Unit, Centre Antoine Lacassagne, 33 Avenue de Valombrose, 06189 Nice Cedex 2, France.