Originally published as JCO Early Release 10.1200/JCO.2004.00.1438 on November 21 2005

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Phase I/IIa Study of Cetuximab With Gemcitabine Plus Carboplatin in Patients With Chemotherapy-Naïve Advanced Non–Small-Cell Lung Cancer

From the University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL; M.D. Anderson Cancer Center, Houston, TX; M.D. Anderson Cancer Center Orlando, FL; Georgia Cancer Specialists, Marietta, GA; and ImClone Systems Inc, Branchburg, NJ.

Address reprint requests to Francisco Robert, MD, University of Alabama at Birmingham, Comprehensive Cancer Center, 1824 6th Ave S, NP-CC 2555D, Birmingham, AL 35294-3300; e-mail: pacorobertuab{at}cs.com

PURPOSE: This multicenter, open-label, phase I/IIa study was undertaken to establish the safety/toxicity profile of cetuximab in combination with gemcitabine and carboplatin in patients with chemotherapy-naïve, epidermal growth factor receptor–positive, stage IV non–small-cell lung cancer. Secondary objectives were to gather preliminary evidence of efficacy including tumor response rate, time to progression, and overall survival.

PATIENTS AND METHODS: Thirty-five patients received a total of 264 3-week cycles of treatment with cetuximab, carboplatin, and gemcitabine. An initial dose of cetuximab 400 mg/m² intravenously was administered the first week, followed by weekly doses of 250 mg/m². Carboplatin (area under the curve = 5, day 1) and gemcitabine 1,000 mg/m² on days 1 and 8 were administered every 3 weeks. Patients were evaluated for tumor response after every two cycles of therapy.

RESULTS: The most frequently reported adverse events related to cetuximab included an acne-like rash (88.6%), dry skin (34.3%), asthenia and skin disorders (31.4%), mucositis/stomatitis (25.7%), fever/chills (20%), and nausea/vomiting (17.1%). The majority of these toxicities were mild to moderate. One patient withdrew from the study because of a grade 3 allergic reaction. Myelosuppression was the most frequently observed toxicity related to chemotherapy. Responses among 35 assessable patients included 10 partial responses (28.6%). Twenty-one patients had stable disease. The median time to progression was 165 days, and the median overall survival was 310 days.

CONCLUSION: The combination of cetuximab, carboplatin, and gemcitabine was well tolerated with an acceptable toxicity profile. Most grade 3 adverse events were attributable to chemotherapy. The response rate and median survival are encouraging and warrant additional investigation.

Supported by a Grant from ImClone Systems Inc.

Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003.

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

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