Background: Preclinical data suggest sequential administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) following chemotherapy may improve efficacy. We hypothesized that intermittent delivery of EGFR-TKI following chemotherapy may increase efficacy.
Methods: This was a multicenter, single-arm phase I/II study to evaluate the efficacy of intermitted erlotinib in combination with docetaxel in patients with EGFR-negative NSCLC who failed one prior chemotherapy. The phase I primary objectives were to determine the maximum tolerated dose (MTD) and recommended dose (RD) of erlotinib. Erlotinib was administered orally once per day on days 2-16 in combination with 60 mg/m2 docetaxel on day1 for 21 days. A standard 3 + 3 dose escalation design was employed for erlotinib from 100 to 150 mg/dose. The phase II primary endpoint was the objective response rate (ORR). The ORR and 95% confidence interval (CI) were calculated using a binomial distribution. This study required 45 patients.
Results: In the phase I part, the planned dose escalation was completed without reaching MTD. The RD of erlotinib was determined as 150 mg/dose. In the phase II part, the ORR and disease control rate were 17.1% (95%CI: 7.2-32.1%) and 53.7% (95%CI: 37.4-69.3%), respectively. Median progression-free survival and overall survival were 3.5 (95%CI: 3.1-4.5) and 11.3 (95%CI: 8.6-16.6) months, respectively. The common non-hematological adverse event was febrile neutropenia (grade 3-4:19.6%). Two treatment-related deaths were occurred because of interstitial lung disease and pleural infection.
Conclusions: Intermittent dosing of erlotinib plus docetaxel is clinically feasible in phase I part but did not significantly improve ORR in phase II part.
Keywords: EGFR negative; NSCLC; docetaxel; erlotinib; sequential.
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