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A phase I trial of gefitinib and nimotuzumab in patients with advanced non-small cell lung cancer (NSCLC)

 Se Hyun Kim  ;  Hyo Sup Shim  ;  Jaeho Cho  ;  Jae Heon Jeong  ;  Sun Mi Kim  ;  Yun Kyoung Hong  ;  Ji Hee Sung  ;  Sang-Jun Ha  ;  Hye Ryun Kim  ;  Hyun Chang  ;  Joo Hang Kim  ;  Crombet Tania  ;  Byoung Chul Cho 
 LUNG CANCER, Vol.79(3) : 270-275, 2013 
Journal Title
Issue Date
Aged ; Antibodies, Monoclonal, Humanized/administration & dosage* ; Antibodies, Monoclonal, Humanized/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Carcinoma, Non-Small-Cell Lung/genetics ; Drug Resistance, Neoplasm ; Female ; Humans ; Lung Neoplasms/drug therapy* ; Lung Neoplasms/genetics ; Male ; Middle Aged ; Mutation/genetics ; Neoplasm Staging ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins p21(ras) ; Quinazolines/administration & dosage* ; Quinazolines/adverse effects ; Receptor, Epidermal Growth Factor/genetics ; Receptor, Epidermal Growth Factor/immunology ; Skin Diseases/etiology ; Treatment Outcome ; ras Proteins/genetics
NSCLC ; EGFR ; Gefitinib ; Nimotuzumab ; Phase I
BACKGROUND: Nimotuzumab (TheraCIM®) is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) with minimal skin toxicity. Combining a different class of anti-EGFR drug with gefitinib is a new strategy to overcome intrinsic and acquired resistance to gefitinib. The aim of this phase I trial was to determine recommended phase II dose (RPIID) and the safety of gefitinib and nimotuzumab combination treatment. METHODS: Patients with advanced/metastatic NSCLC were treated with escalating doses of weekly nimotuzumab (100mg or 200mg, IV) and fixed doses of daily gefitinib (250 mg/day, PO) until disease progression or unacceptable toxicity. We planned to enroll 10 additional patients at RPIID to ascertain the safety of treatment. EGFR mutations and KRAS mutations were analyzed from available tumor samples. RESULTS: A total of 16 patients were enrolled (3 in 100mg cohort, 13 in 200mg cohort). Six patients (37.5%) were female, and 5 (31.3%) were never smokers. Adenocarcinoma was the major histologic type (13 patients, 81.3%). Treatment was well-tolerated without dose-limiting toxicity (DLT). Four patients (25.0%) experienced grade 2 skin toxicity (1 in 100mg cohorts, 3 in 200mg cohort). Other common grade 1/2 toxicities were fatigue (37.5%) and diarrhea (25.0%). Among 16 evaluable patients, four patients (25.0%) achieved partial response and 7 patients (43.8%) had stable disease. Two of 4 responders had EGFR mutation (exon 19 deletion). CONCLUSIONS: Dual agent molecular targeting of EGFR with nimotuzumab and gefitinib in patients with advanced NSCLC is well-tolerated. The RPIID for nimotuzumab is 200mg weekly IV and for gefitinib 250 mg/day PO. Based upon this phase I trial, we are planning to conduct a randomized phase II trial comparing gefitinib and nimotuzumab with gefitinib alone in patients with advanced NSCLC.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sun Mi(김선미)
Kim, Se Hyun(김세현)
Kim, Joo Hang(김주항)
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Chang, Hyun(장현)
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
Cho, Jae Ho(조재호) ORCID logo https://orcid.org/0000-0001-9966-5157
Hong, Yun Kyoung(홍윤경)
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