Originally published as JCO Early Release 10.1200/JCO.2006.07.5754 on January 16 2007

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jackman, D. M. Articles by Jänne, P. A. Search for Related Content PubMed PubMed Citation Articles by Jackman, D. M. Articles by Jänne, P. A. Related Articles Related Editorial

Phase II Clinical Trial of Chemotherapy-Naïve Patients 70 Years of Age Treated With Erlotinib for Advanced Non–Small-Cell Lung Cancer

David M. Jackman, Beow Y. Yeap, Neal I. Lindeman, Panos Fidias, Michael S. Rabin, Jennifer Temel, Arthur T. Skarin, Matthew Meyerson, Alison J. Holmes, Ana M. Borras, Boris Freidlin, Patricia A. Ostler, Joan Lucca, Thomas J. Lynch, Bruce E. Johnson, Pasi A. Jänne

From the Dana-Farber Cancer Institute; Brigham and Women’s Hospital; Massachusetts General Hospital; and Harvard Medical School, Boston, MA

Address reprint requests to Pasi A. Jänne, MD, PhD, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115; e-mail: pjanne{at}partners.org

Purpose: This is a phase II, multicenter, open-label study of chemotherapy-naïve patients with non–small-cell lung cancer (NSCLC) and age 70 years who were treated with erlotinib and evaluated to determine the median, 1-year, and 2-year survival. The secondary end points include radiographic response rate, time to progression (TTP), toxicity, and symptom improvement.

Patients and Methods: Eligible patients with NSCLC were treated with erlotinib 150 mg/d until disease progression or significant toxicity. Tumor response was assessed every 8 weeks by computed tomography scan using Response Evaluation Criteria in Solid Tumors. Tumor samples were analyzed for the presence of somatic mutations in EGFR and KRAS.

Results: Eighty eligible patients initiated erlotinib therapy between March 2003 and May 2005. There were eight partial responses (10%), and an additional 33 patients (41%) had stable disease for 2 months or longer. The median TTP was 3.5 months (95% CI, 2.0 to 5.5 months). The median survival time was 10.9 months (95% CI, 7.8 to 14.6 months). The 1- and 2- year survival rates were 46% and 19%, respectively. The most common toxicities were acneiform rash (79%) and diarrhea (69%). Four patients developed interstitial lung disease of grade 3 or higher, with one treatment-related death. EGFR mutations were detected in nine of 43 patients studied. The presence of an EGFR mutation was strongly correlated with disease control, prolonged TTP, and survival.

Conclusion: Erlotinib monotherapy is active and relatively well tolerated in chemotherapy-naïve elderly patients with advanced NSCLC. Erlotinib merits consideration for further investigation as a first-line therapeutic option in elderly patients.

published online ahead of print at www.jco.org on January 16, 2007.

Supported by Grants No. 1K12CA87723-01 (P.A.J.) and 1RO1CA114465-01 (B.E.J. and P.A.J.) from the National Institutes of Health, Grant No. P20CA90578-02 (B.E.J. and B.Y.Y) from the National Cancer Institute Specialized Program of Research Excellence in Lung Cancer, and a grant from Genentech Inc, as well as by the Doris and William Krupp Research Fund in Thoracic Oncology.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Related Editorial

• Mind Your Elders: Therapeutic Implications of Epidermal Growth Factor Receptor Inhibition in Older Patients With Advanced Non–Small-Cell Lung Cancer
  Corey J. Langer
  JCO 2007 25: 751-753 [Full Text]

This article has been cited by other articles:

				P. Wheatley-Price, K. Ding, L. Seymour, G. M. Clark, and F. A. Shepherd Erlotinib for Advanced Non-Small-Cell Lung Cancer in the Elderly: An Analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21 J. Clin. Oncol., May 10, 2008; 26(14): 2350 - 2357. [Abstract] [Full Text] [PDF]

				G. D'Addario, D. Rauch, R. Stupp, M. Pless, R. Stahel, N. Mach, L. Jost, L. Widmer, C. Tapia, M. Bihl, et al. Multicenter phase II trial of gefitinib first-line therapy followed by chemotherapy in advanced non-small-cell lung cancer (NSCLC): SAKK protocol 19/03 Ann. Onc., April 1, 2008; 19(4): 739 - 745. [Abstract] [Full Text] [PDF]

				N. A. Rizvi, G. J. Riely, C. G. Azzoli, V. A. Miller, K. K. Ng, J. Fiore, G. Chia, M. Brower, R. Heelan, M. J. Hawkins, et al. Phase I/II Trial of Weekly Intravenous 130-nm Albumin-Bound Paclitaxel As Initial Chemotherapy in Patients With Stage IV Non-Small-Cell Lung Cancer J. Clin. Oncol., February 1, 2008; 26(4): 639 - 643. [Abstract] [Full Text] [PDF]

				S. S. Ramalingam, S. E. Dahlberg, C. J. Langer, R. Gray, C. P. Belani, J. R. Brahmer, A. B. Sandler, J. H. Schiller, and D. H. Johnson Outcomes for Elderly, Advanced-Stage Non Small-Cell Lung Cancer Patients Treated With Bevacizumab in Combination With Carboplatin and Paclitaxel: Analysis of Eastern Cooperative Oncology Group Trial 4599 J. Clin. Oncol., January 1, 2008; 26(1): 60 - 65. [Abstract] [Full Text] [PDF]

				S. M. Lichtman Pharmacology of Antineoplastic Agents for Older Patients ASCO Educational Book, January 1, 2008; 2008(1): 210 - 214. [Abstract] [Full Text] [PDF]

				B. E. Johnson, D. Jackman, and P. A. Janne Rationale for a Phase I Trial of Erlotinib and the Mammalian Target of Rapamycin Inhibitor Everolimus (RAD001) for Patients with Relapsed Non Small Cell Lung Cancer Clin. Cancer Res., August 1, 2007; 13(15): 4628s - 4631s. [Abstract] [Full Text] [PDF]

				B. Wacker, T. Nagrani, J. Weinberg, K. Witt, G. Clark, and P. J. Cagnoni Correlation between Development of Rash and Efficacy in Patients Treated with the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib in Two Large Phase III Studies Clin. Cancer Res., July 1, 2007; 13(13): 3913 - 3921. [Abstract] [Full Text] [PDF]

				C. Gridelli, M. A. Bareschino, C. Schettino, A. Rossi, P. Maione, and F. Ciardiello Erlotinib in Non-Small Cell Lung Cancer Treatment: Current Status and Future Development Oncologist, July 1, 2007; 12(7): 840 - 849. [Abstract] [Full Text] [PDF]

				C. J. Langer Mind Your Elders: Therapeutic Implications of Epidermal Growth Factor Receptor Inhibition in Older Patients With Advanced Non-Small-Cell Lung Cancer J. Clin. Oncol., March 1, 2007; 25(7): 751 - 753. [Full Text] [PDF]