Randomized phase II study of paclitaxel/carboplatin intercalated with gefitinib compared to paclitaxel/carboplatin alone for chemotherapy-naïve non-small cell lung cancer in a clinically selected population excluding patients with non-smoking adenocarcinoma or mutated EGFR

BMC Cancer. 2015 Oct 22:15:763. doi: 10.1186/s12885-015-1714-y.

Abstract

Background: Considering cell cycle dependent cytotoxicity, intercalation of chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) may be a treatment option in non-small cell lung cancer (NSCLC). This randomized phase 2 study compared the efficacy of paclitaxel and carboplatin (PC) intercalated with gefitinib (G) versus PC alone in a selected, chemotherapy-naïve population of advanced NSCLC patients with a history of smoking or wild-type EGFR.

Methods: Eligible patients were chemotherapy-naïve advanced NSCLC patients with Eastern Cooperative Oncology Group performance status of 0-2. Non-smoking patients with adenocarcinoma or patients with activating EGFR mutation were excluded because they could benefit from gefitinib alone. Eligible patients were randomized to one of the following treatment arms: PCG, P 175 mg/m(2), and C AUC 5 administered intravenously on day 1 intercalated with G 250 mg orally on days 2 through 15 every 3 weeks for four cycles followed by G 250 mg orally until progressive disease; or PC, same dosing schedule for four cycles only. The primary endpoint was the objective response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity profile.

Results: A total of 90 patients participated in the study. The ORRs were 41.9 % (95 % confidence interval (CI) 27.0-57.9 %) for the PCG arm and 39.5 % (95 % CI 25.0-55.6 %) for the PC arm (P = 0.826). No differences in PFS (4.1 vs. 4.1 months, P = 0.781) or OS (9.3 vs. 10.5 months, P = 0.827) were observed between the PCG and PC arms. Safety analyses showed a similar incidence of drug-related grade 3/4 toxicity. Rash and pruritus were more frequent in the PCG than in the PC arm.

Conclusions: PCG did not improve ORR, PFS, and OS compared to PC chemotherapy alone for NSCLC in a clinically selected population excluding non-smoking adenocarcinoma or mutated EGFR.

Trial registration: The study is registered with ClinicalTrials.gov ( NCT01196234 ). Registration date is 08/09/2010.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Carboplatin / administration & dosage*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • Disease-Free Survival
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Female
  • Follow-Up Studies
  • Gefitinib
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation
  • Paclitaxel / administration & dosage*
  • Prospective Studies
  • Quinazolines / administration & dosage*

Substances

  • Antineoplastic Agents
  • DNA, Neoplasm
  • Quinazolines
  • Carboplatin
  • EGFR protein, human
  • ErbB Receptors
  • Paclitaxel
  • Gefitinib

Associated data

  • ClinicalTrials.gov/NCT01196234