Phase I Results from a Study of Crizotinib in Combination with Erlotinib in Patients with Advanced Nonsquamous Non–Small Cell Lung Cancer
| Autor: | Athanassios Argiris, Steffan N. Ho, Keith D. Eaton, Weiwei Tan, Martin Gutierrez, Francisco Robert, Sai-Hong Ignatius Ou, Ramaswamy Govindan, Gregory A. Otterson, Alain C. Mita, Nicoletta Brega, Tiziana Usari |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Oncology Lung Neoplasms Pyridines Papillary Cardiorespiratory Medicine and Haematology Pharmacology 0302 clinical medicine Carcinoma Non-Small-Cell Lung Antineoplastic Combined Chemotherapy Protocols Bronchiolo-Alveolar Phase I combination trial Tissue Distribution Non-Small-Cell Lung Erlotinib Hydrochloride Lung Cancer EGFR inhibitors Lung Cancer Proto-Oncogene Proteins c-met Middle Aged Prognosis Rash ErbB Receptors EGFR inhibitor Survival Rate Erlotinib 6.1 Pharmaceuticals Lymphatic Metastasis 030220 oncology & carcinogenesis Female medicine.symptom medicine.drug Adult Pulmonary and Respiratory Medicine medicine.medical_specialty Maximum Tolerated Dose Clinical Trials and Supportive Activities Clinical Sciences Oncology and Carcinogenesis Antineoplastic Agents Adenocarcinoma Article 03 medical and health sciences Crizotinib Clinical Research Internal medicine medicine Humans Oncology & Carcinogenesis Adverse effect Lung cancer Protein Kinase Inhibitors MET inhibitor neoplasms Survival rate Aged Neoplasm Staging business.industry Carcinoma Evaluation of treatments and therapeutic interventions Adenocarcinoma Bronchiolo-Alveolar medicine.disease Carcinoma Papillary respiratory tract diseases 030104 developmental biology Drug Resistance Neoplasm Pyrazoles business Follow-Up Studies |
| Zdroj: | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, vol 12, iss 1 J Thorac Oncol |
| ISSN: | 1556-0864 |
| Popis: | Introduction This phase I trial was conducted to determine the safety, maximum tolerated dose (MTD)/recommended phase II dose, and efficacy of crizotinib plus erlotinib in patients with advanced NSCLC. Methods Patients with NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 2 after failure of one or two prior chemotherapy regimens were eligible. Erlotinib, 100 mg, was given continuously once daily starting between day −14 and −7; crizotinib, 200 mg twice daily (dose level 1) or 150 mg twice daily (dose level −1), was added continuously beginning on day 1 of treatment cycle 1. Potential pharmacokinetic interactions between crizotinib and erlotinib were evaluated. Results Twenty-seven patients received treatment; 26 received crizotinib plus erlotinib. Frequent adverse events were diarrhea, rash, decreased appetite, and fatigue. Dose-limiting toxicities were dehydration, diarrhea, dry eye, dysphagia, dyspepsia, esophagitis and vomiting. The MTD was crizotinib, 150 mg twice daily, with erlotinib, 100 mg once daily. Crizotinib increased the erlotinib area under the concentration-time curve 1.5-fold (dose level −1) and 1.8-fold (dose level 1). The plasma level of crizotinib appeared to be unaffected by coadministration of erlotinib. Two patients whose tumors harbored activating EGFR mutations achieved confirmed partial responses, one at each crizotinib dose level. Conclusions The MTD of the combination of crizotinib and erlotinib in patients with advanced NSCLC was crizotinib, 150 mg twice daily, with erlotinib, 100 mg once daily, which is less than the approved dose of either agent. The phase II portion of the study was not initiated. |
| Databáze: | OpenAIRE |
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