Phase I Results from a Study of Crizotinib in Combination with Erlotinib in Patients with Advanced Nonsquamous Non–Small Cell Lung Cancer

Sai Hong Ignatius Ou, Ramaswamy Govindan, Keith D. Eaton, Gregory A. Otterson, Martin E. Gutierrez, Alain C. Mita, Athanassios Argiris, Nicoletta M. Brega, Tiziana Usari, Weiwei Tan, Steffan N. Ho, Francisco Robert

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Introduction This phase I trial was conducted to determine the safety, maximum tolerated dose (MTD)/recommended phase II dose, and efficacy of crizotinib plus erlotinib in patients with advanced NSCLC. Methods Patients with NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 2 after failure of one or two prior chemotherapy regimens were eligible. Erlotinib, 100 mg, was given continuously once daily starting between day −14 and −7; crizotinib, 200 mg twice daily (dose level 1) or 150 mg twice daily (dose level −1), was added continuously beginning on day 1 of treatment cycle 1. Potential pharmacokinetic interactions between crizotinib and erlotinib were evaluated. Results Twenty-seven patients received treatment; 26 received crizotinib plus erlotinib. Frequent adverse events were diarrhea, rash, decreased appetite, and fatigue. Dose-limiting toxicities were dehydration, diarrhea, dry eye, dysphagia, dyspepsia, esophagitis and vomiting. The MTD was crizotinib, 150 mg twice daily, with erlotinib, 100 mg once daily. Crizotinib increased the erlotinib area under the concentration-time curve 1.5-fold (dose level −1) and 1.8-fold (dose level 1). The plasma level of crizotinib appeared to be unaffected by coadministration of erlotinib. Two patients whose tumors harbored activating EGFR mutations achieved confirmed partial responses, one at each crizotinib dose level. Conclusions The MTD of the combination of crizotinib and erlotinib in patients with advanced NSCLC was crizotinib, 150 mg twice daily, with erlotinib, 100 mg once daily, which is less than the approved dose of either agent. The phase II portion of the study was not initiated.

Original languageEnglish (US)
Pages (from-to)145-151
Number of pages7
JournalJournal of Thoracic Oncology
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2017

Keywords

  • Crizotinib
  • EGFR inhibitor
  • Erlotinib
  • MET inhibitor
  • Phase I combination trial

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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