Intermittent chemotherapy and erlotinib for nonsmokers or light smokers with advanced adenocarcinoma of the lung: a phase II clinical trial.

Background: Intermittent application of chemotherapy and tyrosine kinase inhibitors may avoid antagonism between the two classes of drugs. This hypothesis was tested in a Phase II clinical trial.

Patients And Methods: Eligible patients were nonsmokers or light smokers, chemo-naïve, with metastatic adenocarcinoma of the lung.

Treatment: 4 to 6 cycles of gemcitabine 1250 mg/m(2) on days 1 and 4, cisplatin 75 mg/m(2) on day 2, and erlotnib 150 mg daily on days 5-15, followed by erlotinib as maintenance.

Results: 24 patients entered the trial. Four pts had grade 3 toxicity. Complete remission (CR) and partial remission (PR) were seen in 5 pts and 9 pts, respectively (response rate 58%). Median time to progression (TTP) was 13.4 months and median overall survival (OS) was 23 months. When compared to patients with negative or unknown status of EGFR mutations, 8 patients with EGFR gene activating mutations had significantly superior experience: 4 CR and 4 PR, with median TTP 21.5 months and OS 24.2 months (P < .05).

Conclusions: Intermittent schedule with gemcitabine, cisplatin and erlotinib has mild toxicity. For patients who are positive for EGFR gene activating mutations, this treatment offers excellent response rate, time to progression and survival.