As a dose-response relationship has been suggested for cisplatin, it appeared attractive to explore high-dose-intensity regimens in non-small-cell lung cancer. In a phase I study of weekly administration of cisplatin combined with oral etoposide we achieved a cisplatin dose intensity of 52.5-60 mg/m2 per week in most patients. We subsequently explored this regimen in advanced non-small-cell lung cancer. Patients were treated with cisplatin infused at 70 mg/m2 on days 1, 8, 15 and 29, 36, 43 in combination with oral etoposide given at 50 mg on days 1-15 and 29-43. Patients showing stable disease or a better response were continued on treatment with oral etoposide given at 50 mg/m2 per day on days 1-21 every 28 days for a maximum of four cycles. In all, 22 patients with stage III disease and 31 patients with stage IV disease entered the study. The median number of cisplatin administration was 6 per patient; 17 patients reached the planned cisplatin dose intensity of 60 mg/m2 per week, 11 patients achieved 52.5 mg/m2 per week, and 7 patients reached 47 mg/m2 per week. Overall, 11 of 21 stage III patients had a partial response [response rate 51%, 95% confidence interval (CI) 36-81%], as did 9 of 28 patients with stage IV disease (32%; 95% CI 15-49%). Toxicity was mainly hematologic, with leukocytopenia being the most frequent cause of treatment delay. Nephrotoxicity of grade 1 was observed in seven patients. Two patients developed clinical hearing loss. With this schedule a high median cisplatin dose intensity of 52.5-60 mg/m2 per week was reached. The 51% response rate achieved in stage III disease makes this schedule attractive for further exploration; however, it is not recommended for routine use in stage IV disease.

Cisplatin, Dose intensity, Non-small-cell lung cancer, Oral etoposide
dx.doi.org/10.1007/s002800050668, hdl.handle.net/1765/61166
Cancer Chemotherapy and Pharmacology
Department of Neurology

Planting, A.S.Th, Kho, M.M.L, van der Burg, M.E.L, Goey, H, Schellens, J.H.M, van den Bent, M.J, … Verweij, J. (1997). A phase II study of weekly high-dose cisplatin combined with oral etoposide in advanced non-small-cell lung cancer. Cancer Chemotherapy and Pharmacology, 40(4), 347–352. doi:10.1007/s002800050668