Phase I/II study of weekly docetaxel dose escalation in combination with fixed weekly cisplatin and concurrent thoracic radiotherapy in locally advanced non-small cell lung cancer

Cancer Chemother Pharmacol. 2006 Sep;58(3):285-91. doi: 10.1007/s00280-005-0176-3. Epub 2006 Jan 17.

Abstract

Purpose: We conducted a phase I study to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of weekly docetaxel and cisplatin (DOC/CDDP) with concurrent thoracic radiotherapy (TRT) in patients with unresectable stage III non-small-cell lung cancer (NSCLC).

Materials and methods: The DOC/CDDP administration schedules consisted of a split schedule (SS) with administration in 3 out of every 4 weeks, and a continuous schedule (CS) with administration every week. TRT was given to a total dose of 60 Gy at 2 Gy per fraction over 6 weeks.

Results: Twenty-one patients entered the study. The patient characteristics were: PS 0/1/2, 6/13/2; Sq/Ad, 16/5; stage IIIA/IIIB, 4/17. The principal DLT was grade3 esophagitis. The MTD of DOC on the SS and CS in combination with CDDP (25 mg/m2/week) was 25 and 20 mg/m(2)/week, respectively. We determined the RD and schedule of DOC/CDDP on the SS to be 20/25 mg/m(2)/week. The serum alpha-1-acid glycoprotein (AAG) concentration values were found to be negatively correlated with the grade of esophagitis. The median survival time was 23.1 months.

Conclusion: The chemoradiation regimen tested in this study has promising activity and manageable toxicity. The continuous schedule could not be recommended due to excessive toxicity. The main DLT was esophagitis, and it significantly correlated with the plasma AAG concentration.

Publication types

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

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Carcinoma, Non-Small-Cell Lung* / radiotherapy
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Cisplatin / therapeutic use
  • Combined Modality Therapy
  • Disease-Free Survival
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / pathology
  • Lung Neoplasms* / radiotherapy
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Staging
  • Radiation Dosage
  • Taxoids / administration & dosage
  • Taxoids / adverse effects
  • Taxoids / therapeutic use
  • Thorax
  • Treatment Outcome

Substances

  • Taxoids
  • Docetaxel
  • Cisplatin