Phase II study of dose-dense chemotherapy followed by dose-intense erlotinib for initial treatment of metastatic NSCLC.

Abstract

7601 Background: Erlotinib is an effective treatment strategy for patients with NSCLC. Previous trials have associated clinical benefit with pharmacodynamic outcomes such as the development of rash or diarrhea. Maximizing dosing for each individual patient based on their metabolism of erlotinib may be one method to improve outcomes associated with this drug. This study aimed to establish a safe and effective method for intra-patient dose escalation of erlotinib. Methods: Patients with metastatic NSCLC received docetaxel 75 mg/m2 and cisplatin 75 mg/m2 on day1 on a q 2 week cycle for a total of 4 cycles. All patients were given pegfilgrastim growth factor support on day 2. Patients then received erlotinib with initial doses based on current smoking status, 150 mg daily for non-smokers and 300 mg daily for smokers. Erlotinib doses were escalated by 75 mg every 2 weeks until development of grade 2+ non-hematologic toxicity. In the event of grade 2 toxicity, erlotinib was continued at the same dose. In the event of grade 3+ toxicity, doses were held until resolution and restarted after decreasing the dose by 75 mg daily. Results: 45 patients were enrolled from 8/2007 through 1/2011 and enrollment is now completed. Maximal tolerated dose (MTD) of erlotinib achieved ranged from 75 to 525 mg. Maximum doses achieved in smokers was higher than in non-smokers. 91.7% of evaluable patients achieved an MTD prior to being removed from the study. No grade five toxicities or evidence of interstitial lung disease were observed. Preliminary PFS using time to first progression shows a median PFS of 4.6 months (95% CI 3.58 to 5.65). Updated PFS and overall survival will be analyzed and updated in May 2011. Conclusions: A high degree of inter-patient variability exists in erlotinib MTD. Active smokers tolerate a higher dose of erlotinib than non-smokers. The dose-escalation strategy used in this study appears to be safe and effective for individualizing erlotinib dose.