A PHASE-II STUDY OF WEEKLY HIGH-DOSE CISPLATIN COMBINED WITH ORAL ETOPOSIDE IN ADVANCED NON-SMALL-CELL LUNG-CANCER

As a dose-response relationship has been suggested for cisplatin, it a ppeared attractive to explore high dose-intensity regimens in non-smal l-cell lung cancer. In a phase I study of weekly administration of cis platin combined with oral etoposide we achieved a cisplatin dose inten sity of 52.5-60 mg/m(2) per week in most patients. We subsequently exp lored this regimen in advanced non-small-cell lung cancer. Patients we re treated with cisplatin infused at 70 mg/m(2) on days 1, 8, 15 and 2 9, 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 wer e 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 p atients with stage III disease and 31 patients with stage IV disease e ntered the study. The median number of cisplatin administration was 6 per patient; 17 patients reached the planned cisplatin dose intensity of 60 mg/m(2) per week, 11 patients achieved 52.5 mg/m(2) per week, an d 7 patients reached 47 mg/m2 per week. Overall, 11 of 21 stage III pa tients had a partial response [response rate 51%, 95% confidence inter val (CI) 36-81%], as did 9 of 28 patients with stage IV disease (32%; 95% CI 15-49%). Toxicity was mainly hematologic, with leukocytopenia b eing the most frequent cause of treatment delay. Nephrotoxicity of gra de 1 was observed in seven patients. Two patients developed clinical h earing 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 explo ration; however, it is not recommended for routine use in stage IV dis ease.