Prospective assessment of discontinuation and reinitiation of erlotinib or gefitinib in patients with acquired resistance to erlotinib or gefitinib followed by the addition of everolimus Journal Article
| Authors: | Riely, G. J.; Kris, M. G.; Zhao, B.; Akhurst, T.; Milton, D. T.; Moore, E.; Tyson, L.; Pao, W.; Rizvi, N. A.; Schwartz, L. H.; Miller, V. A. |
| Article Title: | Prospective assessment of discontinuation and reinitiation of erlotinib or gefitinib in patients with acquired resistance to erlotinib or gefitinib followed by the addition of everolimus |
| Abstract: | Purpose: Ten percent of U.S. patients with non-small cell lung cancer experience partial radiographic responses to erlotinib or gefitinib. Despite initial regressions, these patients develop acquired resistance to erlotinib or gefitinib. In these patients, we sought to assess changes in tumor metabolism and size after stopping and restarting erlotinib or gefitinib and to determine the effect of adding everolimus. Experimental Design: Patients with non-small cell lung cancer and acquired resistance to erlotinib or gefitinib were eligible. Patients had 18-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography and computed tomography scans at baseline, 3 weeks after stopping erlotinib or gefitinib, and 3 weeks after restarting erlotinib or gefitinib. Three weeks after restarting erlotinib or gefitinib, everolimus was added to treatment. Results: Ten patients completed all four planned studies. Three weeks after stopping erlotinib or gefitinib, there was a median 18% increase in SUVmax and 9% increase in tumor diameter. Three weeks after restarting erlotinib or gefitinib, there was a median 4% decrease in SUVmax and 1% decrease in tumor diameter. No partial responses (0 of 10; 95% confidence interval, 0-31%) were seen with the addition of everolimus to erlotinib or gefitinib. Conclusions: In patients who develop acquired resistance, stopping erlotinib or gefitinib results in symptomatic progression, increase in SUVmax, and increase in tumor size. Symptoms improve and SUVmax decreases after restarting erlotinib or gefitinib, suggesting that some tumor cells remain sensitive to epidermal growth factor receptor blockade. No responses were observed with combined everolimus and erlotinib or gefitinib. We recommend a randomized trial to assess the value of continuing erlotinib or gefitinib after development of acquired resistance. © 2007 American Association for Cancer Research. |
| Keywords: | adult; clinical article; controlled study; treatment outcome; treatment response; aged; aged, 80 and over; middle aged; fatigue; erlotinib; cancer combination chemotherapy; diarrhea; drug withdrawal; monotherapy; antineoplastic agents; positron emission tomography; antineoplastic agent; prospective study; prospective studies; computer assisted tomography; tumor volume; protein kinase inhibitor; lung non small cell cancer; nausea; antineoplastic combined chemotherapy protocols; carcinoma, non-small-cell lung; lung neoplasms; tomography, x-ray computed; combination chemotherapy; drug resistance; drug resistance, neoplasm; cancer resistance; dyspnea; rash; protein kinase inhibitors; lung tumor; cancer regression; diagnostic agent; fluorodeoxyglucose f 18; fluorodeoxyglucose f18; positron-emission tomography; gefitinib; drug derivative; scintiscanning; radiography; quinazolines; epistaxis; everolimus; rapamycin; quinazoline derivative; sirolimus; mouth ulcer |
| Journal Title: | Clinical Cancer Research |
| Volume: | 13 |
| Issue: | 17 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2007-09-01 |
| Start Page: | 5150 |
| End Page: | 5155 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-07-0560 |
| PUBMED: | 17785570 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 43" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus" |
