Reduction of cisplatin dosage by ZD 1839.
Cisplatin (CDDP) is the main chemotherapeutic drug in the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), but its nephrotoxicity often limits the treatment. ZD 1839 is an orally-applicable, selective EGFR tyrosine kinase inhibitor. This investigation explored whether the cisplatin dose can be reduced by the additional application of ZD 1839. Four different SCCHN cell lines were treated with descending doses of CDDP alone or in combination with ZD 1839. Proliferation was measured by the MTT assay; tumor cell toxicity was measured by using the lactate dehydrogenase approach. ZD 1839 augments CDDP-dependent antiproliferative effects. By adding ZD 1839 to the treatment regimen, the CDDP dose could be reduced by up to 25% of the CDDP IC50 dose without compromising the antiproliferative effect. Adding ZD 1839 to CDDP may therefore enable CDDP treatment at a lower dose without compromising antiproliferative effects.
Hambek
Markus
M
Department of Otorhonolaryngology, School of Medicine, J. W. Goethe University, 60590 Frankfurt, Germany.
Baghi
Mehran
M
Strebhardt
Klaus
K
Strebhard
Klaus
K
Baumann
Helena
H
Gstöttner
Wolfgang
W
Knecht
Rainald
R
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D000077156:Gefitinib; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D020128:Inhibitory Concentration 50; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D013778:Tetrazolium Salts; D013844:Thiazoles; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue; D002945:Cisplatin; D000077156:Gefitinib