Triple combination chemotherapy with cisplatin, docetaxel, and irinotecan for advanced non-small cell lung cancer: a phase I/II trial

J Thorac Oncol. 2007 Jan;2(1):44-50. doi: 10.1097/JTO.0b013e31802bafe2.

Abstract

Background: To determine the recommended dose and evaluate the response rate and toxicity of triplet chemotherapy using cisplatin, docetaxel, and irinotecan for non-small cell lung cancer (NSCLC) patients with stage IIIB or IV.

Methods: A total of 65 patients (33 men and 32 women) with advanced NSCLC, a good performance status, and 65 years of age or younger were included in these phase I/II studies. The median age was 52 years. Most patients had performance status 1 (49/65) and stage IV disease (49/65). Adenocarcinoma was the most common tumor histology (55 patients). Cisplatin and docetaxel were given on day 1 and irinotecan on day 2; the cycles were repeated every 3 weeks.

Results: In the phase I study, the maximum tolerated doses of combination cisplatin/docetaxel/irinotecan were, respectively, 80/60/60 (mg/m) and the recommended doses for the phase II study were determined to be 60/60/60 (mg/m), respectively. The dose-limiting toxicities were neutropenia, neutropenic fever, and diarrhea. In the phase II study, 157 cycles of chemotherapy were delivered to 49 patients (median three cycles per patient). The objective response rate was 57.1% (95% confidence interval: 43.1%-71.1%). The median survival time and the actual 2-, 3- and estimated 5-year survival rates were 17 months, 33%, 25%, and 18%, respectively. Grade 3/4 toxicities consisted of neutropenia (92%), neutropenic fever (45%), nausea/vomiting (27%), diarrhea (35%), and hepatic toxicity (2%); there were no cases of treatment-related death.

Conclusion: This triplet chemotherapy has shown a promising activity against advanced NSCLC according to admission-based treatment with adequate supportive care. The principal toxicity was neutropenic fever, but supportive care should be explored to reduce this incidence.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Docetaxel
  • Female
  • Humans
  • Irinotecan
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Survival Rate
  • Taxoids / administration & dosage
  • Taxoids / adverse effects

Substances

  • Taxoids
  • Docetaxel
  • Irinotecan
  • Cisplatin
  • Camptothecin