Phase I study of anti-epidermal growth factor receptor (anti-EGFR) antibody C225 in combination with irradiation in patients with advanced squamous cell carcinoma of the head and neck (SCCHN).
Document Type
Article
Department
Haematology and Oncology, East Africa
Abstract
Purpose/Objective: There is experimental evidence that anti-EGFR monoclonal antibodies (Mabs) enhance the effects of chemotherapy and radiotherapy (RT) on human tumor xenografts expressing EGFR. These studies provide a novel approach to the treatment of advanced SCCHN, a tumor which frequently expresses high levels of EGFR. The purpose of this protocol is to determine the safety profile of different dose levels of the chimeric Mab C225 given concurrently with conventional RT in previously untreated patients (pt) with advanced (stage III and IV) SCCHN. Materials & Methods: Patients receive eight weekly C225 infusions. The initial infusion is a loading dose of either 100, 200, 400 or 500 mg/m 2 (over 60-120.minutes). Subsequent weekly infusions consist of 100, 200, or 250mg/m 2 maintenance dose. Rt (70 Gy at 2 Gy/day) starts on day 8. Three pts are enrolled in each of the four dose levels. Pharmacokinetics, whole body distribution/tumor localization with 1311-C225, human immune response to C225 and tumor response are evaluated. Results: Twelve patients have been treated through the 500mg/m 2 loading dose level. The most significant toxieities that have been observed in this study are: grade 3 or 4 mucositis - nine patients; grade 3 skin toxicity - five patients (4 out of 5 at > 400mg/m 2 level); one pt with reversible grade 4 anaphylaxis approximately three minutes into the first C225 infusion, requiring removal from study. Nine major responses (4 complete and 5 partial responses) have been observed in nine pts who have been reevaluated after completion of therapy. Conclusion: Anti-EGFR antibody C225 at various dose levels appears to have an acceptable safety profile when given 2 concurrently with radiotherapy for advanced SCCHN. The loading dose of 400 - 500mg/m with a weekly maintenance dose of 2 i ....... 250mg/m s felt to be the dose capable of achlewng sustained saturatmn of drug clearance mechanisms and exerting the optimal biologic effect of C225.
Publication (Name of Journal)
International Journal of Radiation Oncology
DOI
https://doi.org/10.1016/S0360-3016(98)80497-5
Recommended Citation
Saleh, M.,
Ezekiel, M.,
Robert, F.,
Meredith, R.,
Spencer, S.,
Newsome, J.,
Peters, G.,
LoBuglio, A.
(1998). Phase I study of anti-epidermal growth factor receptor (anti-EGFR) antibody C225 in combination with irradiation in patients with advanced squamous cell carcinoma of the head and neck (SCCHN).. International Journal of Radiation Oncology, 1(42), 322.
Available at:
https://ecommons.aku.edu/eastafrica_fhs_mc_haematol_oncol/111
Comments
This work was published before the author joined Aga Khan University.