A randomised trial comparing preoperative to perioperative chemotherapy in early-stage non-small-cell lung cancer (IFCT 0002 trial)

Eur J Cancer. 2013 Aug;49(12):2654-64. doi: 10.1016/j.ejca.2013.04.013. Epub 2013 Jun 1.

Abstract

Hypothesis: There will be a detectable increase in overall survival (OS) using preoperative (PRE) as opposed to perioperative (PERI) chemotherapy in resectable StageI-II non-small-cell lung cancer (NSCLC).

Methods: This multicenter, open-label, randomised trial with a 2×2 factorial design first compared two chemotherapy strategies (PRE versus PERI), then two chemotherapy regimens (gemcitabine-cisplatin [GP] versus paclitaxel-carboplatin [TC]). The PRE group received two preoperative cycles followed by two additional preoperative cycles, while the PERI group underwent two preoperative cycles followed by two postoperative cycles, the 3rd and 4th cycles being given only to responders in both cases.

Results: A total of 528 patients were randomised, 267 of which were assigned to the PRE group and 261 to the PERI group. Three-year OS did not differ between the two groups (67.4% and 67.7%, respectively; hazard ratio (HR)=1.01 [0.79-1.30], p=0.92), nor did 3-year disease-free survival, response rates, toxicity, or postoperative mortality. Pathological complete response was observed in 22 (8.2%) and 16 patients (6.1%), respectively. Although quality of life did not differ significantly, chemotherapy compliance was significantly higher in the PRE group. The proportion of responders who received Cycles 3 and 4 was significantly higher in the PRE group (90.4% versus 75.2%, p=0.001). In responders, the dose intensity of Cycles 3 and 4 was higher in the PRE group than in the PERI group (mean relative dose intensity of 90.4% versus 82.6%, respectively; p=0.0007). There was no difference between GP and TC in 3-year OS (HR=0.97 [95% confidence interval (CI): 0.76-1.25], p=0.80) or response rates. However, the regimens' toxicity profiles differed.

Conclusions: This study failed to demonstrate any difference in survival between patients receiving preoperative and perioperative chemotherapy in early-stage NSCLC. The increase from two to four preoperative chemotherapy cycles did not increase the pathological response rate.

Trial registration: ClinicalTrials.gov NCT00198354.

Keywords: Adjuvant chemotherapy; Early-stage; Neo-adjuvant chemotherapy; Non-small-cell lung cancer; Randomised trial.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Carboplatin / adverse effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Combined Modality Therapy
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Gemcitabine
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Neoplasm Staging
  • Neutropenia / chemically induced
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Perioperative Care
  • Preoperative Care
  • Quality of Life
  • Treatment Outcome
  • Vomiting / chemically induced

Substances

  • Deoxycytidine
  • Carboplatin
  • Paclitaxel
  • Cisplatin
  • Gemcitabine

Associated data

  • ClinicalTrials.gov/NCT00198354