Phase II randomized study of daily gefitinib treatment alone or with vinorelbine every 2 weeks in patients with adenocarcinoma of the lung who failed at least 2 regimens of chemotherapy

Abstract

BACKGROUND.The objective of this study was to assess the efficacy of adding chronic, intermittent, low‐dose vinorelbine to gefitinib treatment for patients who had adenocarcinoma of the lung who failed ≥2 regimens of chemotherapy.METHODS.Patients were randomized into 2 arms: Oral gefitinib 250 mg daily (the G arm) or vinorelbine 15 mg/m2 as an intravenous infusion on Day 1 and oral gefitinib 250 mg daily on Days 2 through 14 every 2 weeks (the GV arm). From August 2004 to October 2005, 48 patients were enrolled. Epidermal growth factor receptor (EGFR) exon 18 through 21 nucleotide sequence analysis and fluorescence in situ hybridization were performed in patients who had tumor tissue specimens available for analysis.RESULTS.After randomization, each arm had 24 patients. However, 3 patients refused vinorelbine treatment and were given gefitinib treatment only. Thus, 27 patients received G treatment, and 21 patients received GV treatment. Objective response rates were 55.6% in the G arm and 52.4% in the GV arm. All toxicities in both arms were mild. The 1‐year progression‐free survival rate was 57.1% in the GV arm and 21.2% in the G arm (P = .008). The median survival was 13.3 months in the G arm and 23.4 months in the GV arm (P = .1231). Three of 6 patients (50%) had an exon 19 in‐frame deletion, and 2 of 10 patients had EGFR gene high polysomy or amplification (20%).CONCLUSIONS.Gefitinib was highly effective in ethnic Chinese patients with adenocarcinoma of the lung who failed previous platinum and taxane treatment. The addition of low‐dose vinorelbine every 2 weeks produced a significantly better 1‐year progression‐free survival rate. Cancer 2007. © 2007 American Cancer Society.

Efficacy of Second-line Tyrosine Kinase Inhibitors in the Treatment of Metastatic Advanced Non-small-cell Lung Cancer Harboring Exon 19 and 21 EGFR Mutations

“…The median PFS in our study was close to that of TRUST study with Chinese subpopulation (5.8 vs. 6.4 months). The median OS in our study was 12.4 months (95% Cl, 10.6-14.1 months), which was close to the reported 11.5 months in a phase III study and 13.3 months in a phase II study using TKIs as a second-line in the treatment of advanced NSCLC,25,26 but much shorter than reported 27 months in the study of Rosell R et al 27 The difference may be due to a higher percentage (45.2%) of NSCLC patients with brain metastasis were enrolled in our study, and due to other patients' characteristics discrepancies in different studies.…”

A phase I evaluation of the combination of vinflunine and erlotinib in patients with refractory solid tumors

“…Given the marked toxicity in our patient population, this combination cannot be recommended for further study with these dosing schemas, though several patients had prolonged periods of stable disease including one with MBC and three with head and neck cancers. Another recent study combining a vinca alkaloid with an EGFR inhibitor also demonstrated unacceptable toxicity [22], whereas gefitinib ± vinorelbine in a Chinese population had minimal toxicity and the combination demonstrated improved progression free survival [23]. …”

Use of the Epidermal Growth Factor Receptor Inhibitors Gefitinib, Erlotinib, Afatinib, Dacomitinib, and Icotinib in the Treatment of Non-Small-Cell Lung Cancer: A Systematic Review

“…In several trials, small improvements in pfs were noted in favour of the combination arm, but no statistically significant differences were observed [64][65][66][67]69 . Overall survival followed a similar pattern.…”

“…Symptom control and quality of life were evaluated in the two studies by Chen and colleagues 64,66 . Using the Lung Cancer Symptom Scale, both studies found no difference in symptoms between the two groups.…”