A phase II study of weekly high-dose cisplatin combined with oral etoposide in advanced non-small-cell lung cancer

Cancer Chemother Pharmacol. 1997;40(4):347-52. doi: 10.1007/s002800050668.

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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cisplatin / administration & dosage*
  • Cisplatin / therapeutic use
  • Dose-Response Relationship, Drug
  • Etoposide / administration & dosage*
  • Etoposide / therapeutic use
  • Female
  • Humans
  • Infusions, Intravenous
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • Etoposide
  • Cisplatin