A Phase I/II study of weekly high-dose erlotinib in previously treated patients with nonsmall cell lung cancer Journal Article
| Authors: | Milton, D. T.; Azzoli, C. G.; Heelan, R. T.; Venkatraman, E.; Gomez, J. E.; Kris, M. G.; Krug, L. M.; Pao, W.; Rizvi, N. A.; Dunne, M.; Miller, V. A. |
| Article Title: | A Phase I/II study of weekly high-dose erlotinib in previously treated patients with nonsmall cell lung cancer |
| Abstract: | BACKGROUND. Preclinical studies have suggested that erlotinib at high doses may inhibit additional sites downstream of the epidermal growth factor receptor (EGFR), resulting in greater antitumor efficacy. The objective of this study was to determine the tolerability and efficacy of high-dose erlotinib administered on a weekly schedule to patients with advanced nonsmall cell lung cancer (NSCLC). METHODS. The authors conducted a Phase I/II trial of weekly erlotinib in patients with progressive NSCLC who had received previous chemotherapy. In the Phase I portion, patients were enrolled in 3-patient cohorts at erlotinib dose levels of 1200 mg, 1600 mg, and 2000 mg once weekly. The Phase II portion was designed to determine the major objective response rate of the dose identified in the Phase I portion of the trial. RESULTS. Twenty-seven patients were enrolled. No dose-limiting toxicity was observed. Grade 1 and 2 rash and diarrhea were the principle toxicities, and each occurred in 92% of patients. Among 21 patients who were treated at the Phase II dose of 2000 mg weekly, a single objective response was identified, yielding a response rate of 5% (95% confidence interval, 0.2-22%). For this cohort, the median survival was 9.5 months. The sole radiographic response occurred in a patient whose pretreatment tumor specimen harbored an EGFR exon 19 deletion. CONCLUSIONS. Erlotinib at a dose of 2000 mg administered weekly was tolerated well by these patients with advanced NSCLC. The 5% objective response rate did not reach the stated objective at the interim efficacy analysis, prompting the closure of the study. © 2006 American Cancer Society. |
| Keywords: | mitogen activated protein kinase; protein kinase b; adult; cancer chemotherapy; clinical article; controlled study; aged; aged, 80 and over; middle aged; survival rate; gene mutation; prednisone; clinical trial; drug tolerability; fatigue; erlotinib; diarrhea; drug dose reduction; drug efficacy; side effect; antineoplastic agents; drug megadose; follow up; polymerase chain reaction; controlled clinical trial; phase 2 clinical trial; blood toxicity; lung non small cell cancer; nausea; stomatitis; vomiting; carcinoma, non-small-cell lung; lung neoplasms; dehydration; epidermal growth factor receptor; cohort analysis; weight reduction; lung cancer; receptor, epidermal growth factor; antineoplastic activity; pneumonia; rash; protein kinase inhibitors; alanine aminotransferase; aspartate aminotransferase; survival time; dna; disease progression; thorax radiography; hyperbilirubinemia; loperamide; drug absorption; maximum tolerated dose; phase 1 clinical trial; drug dose regimen; quinazolines; tetracycline; minocycline; nonsmall cell lung carcinoma; diphenhydramine; clindamycin; high dose; phase i/ii; sulfadiazine silver; tarceva™ |
| Journal Title: | Cancer |
| Volume: | 107 |
| Issue: | 5 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2006-09-01 |
| Start Page: | 1034 |
| End Page: | 1041 |
| Language: | English |
| DOI: | 10.1002/cncr.22088 |
| PUBMED: | 16878326 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 21" - "Export Date: 4 June 2012" - "CODEN: CANCA" - "Source: Scopus" |
