title: A phase II study of weekly high-dose cisplatin combined with oral etoposide in advanced non-small-cell lung cancer.
abstract: 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.
authors.affiliation: Department of Medical Oncology, Rotterdam Cancer Institute/University Hospital Rotterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Planting
authors.forename: S
authors.initials: S
authors.lastname: Kho
authors.forename: M
authors.initials: M
authors.lastname: van der Burg
authors.forename: H
authors.initials: H
authors.lastname: Goey
authors.forename: J
authors.initials: J
authors.lastname: Schellens
authors.forename: M
authors.initials: M
authors.lastname: van den Bent
authors.forename: A
authors.initials: A
authors.lastname: van der Gaast
authors.forename: M
authors.initials: M
authors.lastname: de Boer-Dennert
authors.forename: G
authors.initials: G
authors.lastname: Stoter
authors.forename: J
authors.initials: J
authors.lastname: Verweij
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D002945:Cisplatin