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Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer
Published on: February 12, 2017
Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with
J Baselga1, D Pfister, M R Cooper
1Department of Medicine, Breast Cancer Medicine and Genitourinary Medicine Services, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. baselga@hg.vhebron.es
Purpose:
The epidermal growth factor (EGF) receptor is frequently overexpressed in epithelial tumors. C225 is a human-to-murine chimeric monoclonal antibody that binds to the receptor and inhibits growth of cancer cells expressing the receptor. We evaluated the pharmacokinetics and toxicity of C225 in patients with advanced tumors overexpressing EGF receptors.
Patients And Methods:
We treated 52 patients in three successive phase I clinical trials of C225 as a single dose (n = 13), weekly multiple dose (n = 17), and weekly multiple dose with cisplatin (n = 22). C225 dose levels were 5, 20, 50, and 100 mg/m(2). In the study combining C225 with cisplatin, limited to patients with either head and neck or non-small-cell lung cancer, C225 was further escalated to 200 and 400 mg/m(2). Cisplatin was given at a dose of 60 mg/m(2) once every 4 weeks, and treatment was continued for up to 12 weeks if no disease progression occurred.
Results:
C225 displayed nonlinear pharmacokinetics, with antibody doses in the range of 200 to 400 mg/m(2) being associated with complete saturation of systemic clearance. C225 clearance did not change with repeated administration or with coadministration of cisplatin. Antibodies against C225 were detected in only one patient, and C225-associated toxicity was minimal. Patients experiencing disease stabilization were seen in all studies. In the study combining C225 and cisplatin, nine (69%) of 13 patients treated with antibody doses >/= 50 mg/m(2) completed 12 weeks of therapy, and two partial responses were observed.
Conclusion:
C225 has dose-dependent pharmacokinetics, and doses that achieve saturation of systemic clearance are well tolerated. C225 given in combination with cisplatin has biologic activity at pharmacologically relevant doses.
Insights
This study evaluated C225, an antibody targeting the epidermal growth factor (EGF) receptor, in cancer patients. Higher C225 doses showed dose-dependent pharmacokinetics and were well-tolerated, with some patients experiencing disease stabilization.
Area of Science:
- Oncology
- Pharmacology
- Immunotherapy
Background:
- Epidermal Growth Factor (EGF) receptor is overexpressed in various epithelial tumors.
- C225 is a chimeric monoclonal antibody targeting the EGF receptor, inhibiting cancer cell growth.
Purpose of the Study:
- To evaluate the pharmacokinetics and toxicity of C225 in patients with advanced tumors overexpressing EGF receptors.
- To assess the safety and tolerability of C225 as a single agent and in combination with cisplatin.
Main Methods:
- 52 patients with advanced tumors participated in three Phase I clinical trials.
- Treatment involved escalating doses of C225, administered alone or with cisplatin.
- Pharmacokinetic and toxicity profiles were assessed throughout the trials.
Main Results:
- C225 exhibited nonlinear pharmacokinetics, with dose-dependent clearance saturation at 200-400 mg/m².
- C225 was well-tolerated with minimal toxicity and no significant impact from repeated administration or cisplatin.
- Disease stabilization was observed across studies, with partial responses noted in the C225-cisplatin combination arm.
Conclusions:
- C225 demonstrates dose-dependent pharmacokinetics and achieves systemic clearance saturation at well-tolerated doses.
- Combination therapy with C225 and cisplatin shows biologic activity at pharmacologically relevant doses.
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