help button home button The Oncologist
HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow eLetters: Submit a response to this article
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article link to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Reprints/Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cohen, M. H.
Right arrow Articles by Pazdur, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cohen, M. H.
Right arrow Articles by Pazdur, R.
The Oncologist, Vol. 8, No. 4, 303–306, August 2003
© 2003 AlphaMed Press

FDA COMMENTARY

FDA Drug Approval Summary: Gefitinib (ZD1839) (Iressa®) Tablets

Martin H. Cohen, Grant A. Williams, Rajeshwari Sridhara, Gang Chen, Richard Pazdur

Division of Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Rockville, Maryland, USA

Correspondence: Martin H. Cohen, M.D., U.S. Food and Drug Administration, HFD-150, 5600 Fishers Lane, Rockville, Maryland 20857, USA. Fax: 301-594-0499; e-mail: cohenma{at}cder.fda.gov

On May 5, 2003, gefitinib (Iressa®, ZD1839) 250-mg tablets received accelerated approval by the U.S. Food and Drug Administration as monotherapy treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of both platinum-based and docetaxel chemotherapies. Information provided in this summary includes efficacy and safety results of relevant clinical trials. Effectiveness was demonstrated in a randomized, double-blind, phase II, multicenter trial comparing two oral doses of gefitinib (250 mg/day versus 500 mg/day). Two hundred sixteen patients were enrolled. The 142 patients who were refractory to or intolerant of a platinum and docetaxel comprised the evaluable population for the efficacy analysis. A partial tumor response occurred in 14% (9 of 66) of patients receiving gefitinib 250 mg/day and in 8% (6 of 76) of patients receiving gefitinib 500 mg/day. The overall objective response rate for both doses combined was 10.6% (15 of 142 patients) (95% confidence interval 6.0%–16.8%). Responses were more frequent in females and in nonsmokers. The median duration of response was 7.0 months (range 4.6–18.6+ months).

Other submitted data included the results of two large trials conducted in chemotherapy-naive, stage III and IV NSCLC patients. Patients were randomized to receive gefitinib (250 mg or 500 mg daily) or placebo, in combination with either gemcitabine plus cisplatin (n = 1,093) or carboplatin plus paclitaxel (n = 1,037). Results from those studies showed no benefit (response rate, time to progression, or survival) from adding gefitinib to chemotherapy. Consequently, gefinitib is only recommended for use as monotherapy. Common adverse events associated with gefitinib treatment included diarrhea, rash, acne, dry skin, nausea, and vomiting. Most toxicities were Common Toxicity Criteria grade 1 or 2. Interstitial lung disease (ILD) has been observed in patients receiving gefitinib. Worldwide, the incidence of ILD is about 1% (2% in the Japanese postmarketing experience and about 0.3% in a U.S. expanded access program). Approximately one-third of the cases were fatal. Physicians should promptly evaluate new or worsening pulmonary symptoms. If ILD is confirmed, appropriate management includes discontinuation of gefitinib. Gefitinib was approved under accelerated approval regulations on the basis of a surrogate end point response rate. No controlled gefitinib trials, to date, demonstrate a clinical benefit, such as improvement in disease-related symptoms or greater survival. Accelerated approval regulations require the sponsor to conduct further studies to verify that gefitinib therapy produces such a benefit.

Key Words. Gefitinib • Iressa® • Non-small cell lung cancer, metastatic • Third-line treatment




This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
C. M. Rudin, E. Avila-Tang, C. C. Harris, J. G. Herman, F. R. Hirsch, W. Pao, A. G. Schwartz, K. H. Vahakangas, and J. M. Samet
Lung Cancer in Never Smokers: Molecular Profiles and Therapeutic Implications
Clin. Cancer Res., September 15, 2009; 15(18): 5646 - 5661.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
I. Y.-S. Tam, E. L.-H. Leung, V. P.-C. Tin, D. T.-T. Chua, A. D.-L. Sihoe, L.-C. Cheng, L.-P. Chung, and M. P. Wong
Double EGFR mutants containing rare EGFR mutant types show reduced in vitro response to gefitinib compared with common activating missense mutations
Mol. Cancer Ther., August 1, 2009; 8(8): 2142 - 2151.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K.-K. Wong, P. M. Fracasso, R. M. Bukowski, T. J. Lynch, P. N. Munster, G. I. Shapiro, P. A. Janne, J. P. Eder, M. J. Naughton, M. J. Ellis, et al.
A Phase I Study with Neratinib (HKI-272), an Irreversible Pan ErbB Receptor Tyrosine Kinase Inhibitor, in Patients with Solid Tumors
Clin. Cancer Res., April 1, 2009; 15(7): 2552 - 2558.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
T. E. Stinchcombe and M. A. Socinski
Gefitinib in Advanced Non-Small Cell Lung Cancer: Does It Deserve a Second Chance?
Oncologist, September 1, 2008; 13(9): 933 - 944.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
A. J. Gonzales, K. E. Hook, I. W. Althaus, P. A. Ellis, E. Trachet, A. M. Delaney, P. J. Harvey, T. A. Ellis, D. M. Amato, J. M. Nelson, et al.
Antitumor activity and pharmacokinetic properties of PF-00299804, a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor
Mol. Cancer Ther., July 1, 2008; 7(7): 1880 - 1889.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
L. O. T. Gainkam, L. Huang, V. Caveliers, M. Keyaerts, S. Hernot, I. Vaneycken, C. Vanhove, H. Revets, P. De Baetselier, and T. Lahoutte
Comparison of the Biodistribution and Tumor Targeting of Two 99mTc-Labeled Anti-EGFR Nanobodies in Mice, Using Pinhole SPECT/Micro-CT
J. Nucl. Med., May 1, 2008; 49(5): 788 - 795.
[Abstract] [Full Text] [PDF]

Home page
 aacredbookHome page
D. Sachdev and D. Yee
Disrupting Insulin-Like Growth Factor Signaling as a Potential Cancer Therapy
Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 39 - 58.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
J. Verweij
Other Endpoints in Screening Studies for Soft Tissue Sarcomas
Oncologist, April 1, 2008; 13(suppl_2): 27 - 31.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
B. Vahid and P. E. Marik
Pulmonary Complications of Novel Antineoplastic Agents for Solid Tumors*
Chest, February 1, 2008; 133(2): 528 - 538.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. P. Jani, R. S. Finn, M. Campbell, K. G. Coleman, R. D. Connell, N. Currier, E. O. Emerson, E. Floyd, S. Harriman, J. C. Kath, et al.
Discovery and Pharmacologic Characterization of CP-724,714, a Selective ErbB2 Tyrosine Kinase Inhibitor
Cancer Res., October 15, 2007; 67(20): 9887 - 9893.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
V. Liu, D. A. White, M. F. Zakowski, W. Travis, M. G. Kris, M. S. Ginsberg, V. A. Miller, and C. G. Azzoli
Pulmonary Toxicity Associated With Erlotinib
Chest, September 1, 2007; 132(3): 1042 - 1044.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
X. Zhang and A. Chang
Somatic mutations of the epidermal growth factor receptor and non-small-cell lung cancer
J. Med. Genet., March 1, 2007; 44(3): 166 - 172.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
D. Sachdev and D. Yee
Disrupting insulin-like growth factor signaling as a potential cancer therapy
Mol. Cancer Ther., January 1, 2007; 6(1): 1 - 12.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
D. Arnold, S. Peinert, W. Voigt, and H.-J. Schmoll
Epidermal growth factor receptor tyrosine kinase inhibitors: present and future role in gastrointestinal cancer treatment: a review.
Oncologist, June 1, 2006; 11(6): 602 - 611.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
I. Dimopoulou, A. Bamias, P. Lyberopoulos, and M. A. Dimopoulos
Pulmonary toxicity from novel antineoplastic agents
Ann. Onc., March 1, 2006; 17(3): 372 - 379.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
L. S. Kirschner
Emerging Treatment Strategies for Adrenocortical Carcinoma: A New Hope
J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 14 - 21.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. L. Rothenberg, B. LaFleur, D. E. Levy, M. K. Washington, S. L. Morgan-Meadows, R. K. Ramanathan, J. D. Berlin, A. B. Benson III, and R. J. Coffey
Randomized Phase II Trial of the Clinical and Biological Effects of Two Dose Levels of Gefitinib in Patients With Recurrent Colorectal Adenocarcinoma
J. Clin. Oncol., December 20, 2005; 23(36): 9265 - 9274.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
M. G. Kris
How Today's Developments in the Treatment of Non-Small Cell Lung Cancer Will Change Tomorrow's Standards of Care
Oncologist, October 1, 2005; 10(suppl_2): 23 - 29.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. A. Ferguson, M. R. Muenster, Q. Zang, J. A. Spencer, J. J. Schageman, Y. Lian, H. R. Garner, R. B. Gaynor, J. W. Huff, A. Pertsemlidis, et al.
Selective Identification of Secreted and Transmembrane Breast Cancer Markers using Escherichia coli Ampicillin Secretion Trap
Cancer Res., September 15, 2005; 65(18): 8209 - 8217.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Jain, C. A. Tindell, I. Laux, J. B. Hunter, J. Curran, A. Galkin, D. E. Afar, N. Aronson, S. Shak, R. B. Natale, et al.
Epithelial membrane protein-1 is a biomarker of gefitinib resistance
PNAS, August 16, 2005; 102(33): 11858 - 11863.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
X.-T. Zhang, L.-Y. Li, X.-L. Mu, Q.-C. Cui, X.-Y. Chang, W. Song, S.-L. Wang, M.-Z. Wang, W. Zhong, and L. Zhang
The EGFR mutation and its correlation with response of gefitinib in previously treated Chinese patients with advanced non-small-cell lung cancer
Ann. Onc., August 1, 2005; 16(8): 1334 - 1342.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
S Leibl and F Moinfar
Metaplastic breast carcinomas are negative for Her-2 but frequently express EGFR (Her-1): potential relevance to adjuvant treatment with EGFR tyrosine kinase inhibitors?
J. Clin. Pathol., July 1, 2005; 58(7): 700 - 704.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
X. L. Mu, L. Y. Li, X. T. Zhang, M. Z. Wang, R. E. Feng, Q. C. Cui, H. S. Zhou, and B. Q. Guo
Gefitinib-Sensitive Mutations of the Epidermal Growth Factor Receptor Tyrosine Kinase Domain in Chinese Patients with Non-Small Cell Lung Cancer
Clin. Cancer Res., June 15, 2005; 11(12): 4289 - 4294.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
C. Gridelli, M. Aapro, A. Ardizzoni, L. Balducci, F. De Marinis, K. Kelly, T. Le Chevalier, C. Manegold, F. Perrone, R. Rosell, et al.
Treatment of Advanced Non-Small-Cell Lung Cancer in the Elderly: Results of an International Expert Panel
J. Clin. Oncol., May 1, 2005; 23(13): 3125 - 3137.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
M. K. Mohamed, S. Ramalingam, Y. Lin, W. Gooding, and C. P. Belani
Skin rash and good performance status predict improved survival with gefitinib in patients with advanced non-small cell lung cancer
Ann. Onc., May 1, 2005; 16(5): 780 - 785.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
N. C. Nagaria, J. Cogswell, J. K. Choe, and B. Kasimis
Side Effects and Good Effects from New Chemotherapeutic Agents: CASE 1. Gefitinib-Induced Interstitial Fibrosis
J. Clin. Oncol., April 1, 2005; 23(10): 2423 - 2424.
[Full Text] [PDF]

Home page
 JCOHome page
A. Marchetti, C. Martella, L. Felicioni, F. Barassi, S. Salvatore, A. Chella, P. P. Camplese, T. Iarussi, F. Mucilli, A. Mezzetti, et al.
EGFR Mutations in Non-Small-Cell Lung Cancer: Analysis of a Large Series of Cases and Development of a Rapid and Sensitive Method for Diagnostic Screening With Potential Implications on Pharmacologic Treatment
J. Clin. Oncol., February 1, 2005; 23(4): 857 - 865.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
C.M. Canil, M.J. Moore, E. Winquist, T. Baetz, M. Pollak, K.N. Chi, S. Berry, D.S. Ernst, L. Douglas, M. Brundage, et al.
Randomized Phase II Study of Two Doses of Gefitinib in Hormone-Refractory Prostate Cancer: A Trial of the National Cancer Institute of Canada-Clinical Trials Group
J. Clin. Oncol., January 20, 2005; 23(3): 455 - 460.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
N. T. Shah, M. G. Kris, W. Pao, L. B. Tyson, B. M. Pizzo, M.-H. Heinemann, L. Ben-Porat, D. L. Sachs, R. T. Heelan, and V. A. Miller
Practical Management of Patients With Non-Small-Cell Lung Cancer Treated With Gefitinib
J. Clin. Oncol., January 1, 2005; 23(1): 165 - 174.
[Abstract] [Full Text] [PDF]

Home page
 Arch Otolaryngol Head Neck SurgHome page
B. Bostrom, J. Sidman, S. Marker, T. Lander, and D. Drehner
Gefitinib Therapy for Life-Threatening Laryngeal Papillomatosis
Arch Otolaryngol Head Neck Surg, January 1, 2005; 131(1): 64 - 67.
[Full Text] [PDF]

Home page
 ChestHome page
C.-K. Toh, E.-H. Wong, W.-T. Lim, S.-S. Leong, K.-W. Fong, J. Wee, and E.-H. Tan
The Impact of Smoking Status on the Behavior and Survival Outcome of Patients With Advanced Non-small Cell Lung Cancer: A Retrospective Analysis
Chest, December 1, 2004; 126(6): 1750 - 1756.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
T. Herget, M. Freitag, M. Morbitzer, R. Kupfer, T. Stamminger, and M. Marschall
Novel Chemical Class of pUL97 Protein Kinase-Specific Inhibitors with Strong Anticytomegaloviral Activity
Antimicrob. Agents Chemother., November 1, 2004; 48(11): 4154 - 4162.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
R. Dagher, J. Johnson, G. Williams, P. Keegan, and R. Pazdur
Accelerated Approval of Oncology Products: A Decade of Experience
J Natl Cancer Inst, October 20, 2004; 96(20): 1500 - 1509.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
K. Yanase, S. Tsukahara, S. Asada, E. Ishikawa, Y. Imai, and Y. Sugimoto
Gefitinib reverses breast cancer resistance protein-mediated drug resistance
Mol. Cancer Ther., September 1, 2004; 3(9): 1119 - 1125.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. L. Dominguez-Escrig, J. D. Kelly, D. E. Neal, S. M. King, and B. R. Davies
Evaluation of the Therapeutic Potential of the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Gefitinib in Preclinical Models of Bladder Cancer
Clin. Cancer Res., July 15, 2004; 10(14): 4874 - 4884.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
W. R. Parulekar and E. A. Eisenhauer
Phase I Trial Design for Solid Tumor Studies of Targeted, Non-Cytotoxic Agents: Theory and Practice
J Natl Cancer Inst, July 7, 2004; 96(13): 990 - 997.
[Abstract] [Full Text] [PDF]

Home page
 Annals of Clinical & Laboratory ScienceHome page
R. E. Brown, M. Lun, J. W. Prichard, T. M. Blasick, and P. L. Zhang
Morphoproteomic and Pharmacoproteomic Correlates in Hormone-Receptor-Negative Breast Carcinoma Cell Lines
Ann. Clin. Lab. Sci., July 1, 2004; 34(3): 251 - 262.
[Abstract] [Full Text] [PDF]

Home page
 AM J HOSP PALLIAT CAREHome page
E. Prommer
Gefitinib: A new agent in palliative care
American Journal of Hospice and Palliative Medicine, May 1, 2004; 21(3): 222 - 227.
[Abstract] [PDF]

Home page
 JCOHome page
T. Crombet, M. Osorio, T. Cruz, C. Roca, R. del Castillo, R. Mon, N. Iznaga-Escobar, R. Figueredo, J. Koropatnick, E. Renginfo, et al.
Use of the Humanized Anti-Epidermal Growth Factor Receptor Monoclonal Antibody h-R3 in Combination With Radiotherapy in the Treatment of Locally Advanced Head and Neck Cancer Patients
J. Clin. Oncol., May 1, 2004; 22(9): 1646 - 1654.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
M. G. Kris, A. C. Kay, J. J. Ochs, and M. K. Wolf
Predictors of Clinical Response of Non-Small Cell Cancer to Gefitinib--Reply
JAMA, April 7, 2004; 291(13): 1563 - 1564.
[Full Text] [PDF]

Home page
 Cancer Res.Home page
J. P. Carson, N. Zhang, G. M. Frampton, N. P. Gerry, M. E. Lenburg, and M. F. Christman
Pharmacogenomic Identification of Targets for Adjuvant Therapy with the Topoisomerase Poison Camptothecin
Cancer Res., March 15, 2004; 64(6): 2096 - 2104.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
V. A. Miller, M. G. Kris, N. Shah, J. Patel, C. Azzoli, J. Gomez, L. M. Krug, W. Pao, N. Rizvi, B. Pizzo, et al.
Bronchioloalveolar Pathologic Subtype and Smoking History Predict Sensitivity to Gefitinib in Advanced Non-Small-Cell Lung Cancer
J. Clin. Oncol., March 15, 2004; 22(6): 1103 - 1109.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Lu, H. Zhang, D. Ludwig, A. Persaud, X. Jimenez, D. Burtrum, P. Balderes, M. Liu, P. Bohlen, L. Witte, et al.
Simultaneous Blockade of Both the Epidermal Growth Factor Receptor and the Insulin-like Growth Factor Receptor Signaling Pathways in Cancer Cells with a Fully Human Recombinant Bispecific Antibody
J. Biol. Chem., January 23, 2004; 279(4): 2856 - 2865.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
C. L. Sawyers
Opportunities and challenges in the development of kinase inhibitor therapy for cancer
Genes & Dev., December 15, 2003; 17(24): 2998 - 3010.
[Full Text] [PDF]


HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
THE ONCOLOGIST STEM CELLS CME ALPHAMED PRESS JOURNALS


Copyright © 2003 by AlphaMed Press.