Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected].

PURPOSE To evaluate the efficacy and tolerability of two doses of gefitinib (Iressa [ZD1839]; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with pretreated advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS This was a randomized, double-blind, parallel-group, multicenter phase II trial. Two hundred ten patients with advanced NSCLC who were previously treated with one or two chemotherapy regimens (at least one containing platinum) were randomly assigned to receive either 250-mg or 500-mg oral doses of gefitinib once daily. RESULTS Efficacy was similar for the 250- and 500-mg/d groups. Objective tumor response rates were 18.4% (95% confidence interval [CI], 11.5 to 27.3) and 19.0% (95% CI, 12.1 to 27.9); among evaluable patients, symptom improvement rates were 40.3% (95% CI, 28.5 to 53.0) and 37.0% (95% CI, 26.0 to 49.1); median progression-free survival times were 2.7 and 2.8 months; and median overall survival times were 7.6 and 8.0 months, respectively. Symptom improvements were recorded for 69.2% (250 mg/d) and 85.7% (500 mg/d) of patients with a tumor response. Adverse events (AEs) at both dose levels were generally mild (grade 1 or 2) and consisted mainly of skin reactions and diarrhea. Drug-related toxicities were more frequent in the higher-dose group. Withdrawal due to drug-related AEs was 1.9% and 9.4% for patients receiving gefitinib 250 and 500 mg/d, respectively. CONCLUSION Gefitinib showed clinically meaningful antitumor activity and provided symptom relief as second- and third-line treatment in these patients. At 250 mg/d, gefitinib had a favorable AE profile. Gefitinib 250 mg/d is an important, novel treatment option for patients with pretreated advanced NSCLC [corrected]

[1]  K. Pavelić,et al.  Evidence for a role of EGF receptor in the progression of human lung carcinoma. , 1993, Anticancer research.

[2]  M. Kris,et al.  Randomized Phase III Trial of Docetaxel Versus Vinorelbine or Ifosfamide in Patients With Advanced Non–Small-Cell Lung Cancer Previously Treated With Platinum-Containing Chemotherapy Regimens , 2000 .

[3]  N. Normanno,et al.  Epidermal growth factor-related peptides and their receptors in human malignancies. , 1995, Critical reviews in oncology/hematology.

[4]  S. Pocock,et al.  Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. , 1975, Biometrics.

[5]  F. Fossella,et al.  Management strategies for recurrent non-small cell lung cancer. , 1997, Seminars in oncology.

[6]  Stephanie Green,et al.  Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria , 1992, Investigational New Drugs.

[7]  D. Tulsky,et al.  Reliability and validity of the Functional Assessment of Cancer Therapy-Lung (FACT-L) quality of life instrument. , 1995, Lung cancer.

[8]  M. Kris,et al.  Docetaxel (Taxotere) shows survival and quality-of-life benefits in the second-line treatment of non-small cell lung cancer: A review of two phase III trials. , 2001, Seminars in oncology.

[9]  M. Paesmans,et al.  Response to chemotherapy, quality of life benefits and survival in advanced non-small cell lung cancer: review of literature results. , 2001, Lung cancer.

[10]  J. Schiller,et al.  Current Standards of Care in Small-Cell and Non-Small-Cell Lung Cancer , 2001, Oncology.

[11]  D. Lawrence,et al.  Protein kinase inhibitors: the tyrosine-specific protein kinases. , 1998, Pharmacology & therapeutics.

[12]  E. Dmitrovsky,et al.  Overexpression of the epidermal growth factor receptor and its ligand transforming growth factor alpha is frequent in resectable non-small cell lung cancer but does not predict tumor progression. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[13]  M. Kris,et al.  ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  E. Dmitrovsky,et al.  Differential expression of the epidermal growth factor receptor and its ligands in primary non-small cell lung cancers and adjacent benign lung. , 1993, Cancer research.

[15]  M. Volm,et al.  Prognostic value of ERBB-1, VEGF, cyclin A, FOS, JUN and MYC in patients with squamous cell lung carcinomas. , 1998, British Journal of Cancer.

[16]  G. Giaccone,et al.  Second-line chemotherapy in relapsing or refractory non-small-cell lung cancer: a review. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  M. Kris,et al.  Objective regressions in non-small cell lung cancer patients treated in Phase I trials of oral ZD1839 (IressaTM), a selective tyrosine kinase inhibitor that blocks the epidermal growth factor receptor (EGFR) , 2000 .

[18]  J. Dancey,et al.  Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  H. Kato,et al.  A comparison of epidermal growth factor receptor levels and other prognostic parameters in non-small cell lung cancer. , 1996, European journal of cancer.

[20]  D. Cella,et al.  What is a clinically meaningful change on the Functional Assessment of Cancer Therapy-Lung (FACT-L) Questionnaire? Results from Eastern Cooperative Oncology Group (ECOG) Study 5592. , 2002, Journal of clinical epidemiology.