RESUMEN
BACKGROUND: Advanced pancreatic cancer has a poor prognosis, and the current standard of care (gemcitabine based chemotherapy) provides a small survival advantage. However the drawback is the accompanying systemic toxicity, which targeted treatments may overcome. This study aimed to evaluate the safety and tolerability of KAb201, an anti-carcinoembryonic antigen monoclonal antibody, labelled with I(131) in pancreatic cancer (ISRCTN 16857581). METHODS: Patients with histological/cytological proven inoperable adenocarcinoma of the head of pancreas were randomised to receive KAb 201 via either the intra-arterial or intravenous delivery route. The dose limiting toxicities within each group were determined. Patients were assessed for safety and efficacy and followed up until death. RESULTS: Between February 2003 and July 2005, 25 patients were enrolled. Nineteen patients were randomised, 9 to the intravenous and 10 to the intra-arterial arms. In the intra-arterial arm, dose limiting toxicity was seen in 2/6 (33%) patients at 50 mCi whereas in the intravenous arm, dose limiting toxicity was noted in 1/6 patients at 50 mCi, but did not occur at 75 mCi (0/3).The overall response rate was 6% (1/18). Median overall survival was 5.2 months (95% confidence interval = 3.3 to 9 months), with no significant difference between the intravenous and intra-arterial arms (log rank test p = 0.79). One patient was still alive at the time of this analysis. CONCLUSION: Dose limiting toxicity for KAb201 with I(131) by the intra-arterial route was 50 mCi, while dose limiting toxicity was not reached in the intravenous arm.
Asunto(s)
Adenocarcinoma/diagnóstico por imagen , Antígeno Carcinoembrionario/administración & dosificación , Inmunotoxinas/administración & dosificación , Radioisótopos de Yodo/administración & dosificación , Neoplasias Pancreáticas/radioterapia , Radioinmunoterapia/métodos , Adenocarcinoma/inmunología , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacocinética , Anticuerpos Antineoplásicos/biosíntesis , Anticuerpos Antineoplásicos/inmunología , Antígeno Carcinoembrionario/efectos adversos , Antígeno Carcinoembrionario/inmunología , Humanos , Inmunotoxinas/efectos adversos , Inmunotoxinas/inmunología , Inmunotoxinas/farmacocinética , Infusiones Intraarteriales , Infusiones Intravenosas , Radioisótopos de Yodo/efectos adversos , Radioisótopos de Yodo/farmacocinética , Persona de Mediana Edad , Neoplasias Pancreáticas/inmunología , Radiografía , Radioinmunoterapia/efectos adversos , Tasa de SupervivenciaRESUMEN
Chimeric T84.66 (cT84.66) is a high affinity anti-carcinoembryonic antigen (CEA) immunoglobulin G1, that is being developed by City of Hope for the potential treatment of CEA-expressing malignancies.
Asunto(s)
Antígeno Carcinoembrionario/uso terapéutico , Inmunoglobulina G/uso terapéutico , Neoplasias de la Mama/terapia , Antígeno Carcinoembrionario/efectos adversos , Antígeno Carcinoembrionario/metabolismo , Neoplasias Colorrectales/terapia , Femenino , Humanos , Inmunoglobulina G/efectos adversos , Inmunoglobulina G/metabolismo , Masculino , Radioinmunoterapia/métodos , Relación Estructura-Actividad , Radioisótopos de ItrioAsunto(s)
Adenocarcinoma/terapia , Vacunas contra el Cáncer/uso terapéutico , Antígeno Carcinoembrionario/uso terapéutico , Neoplasias Colorrectales/terapia , Adenocarcinoma/secundario , Animales , Vacunas contra el Cáncer/efectos adversos , Vacunas contra el Cáncer/genética , Vacunas contra el Cáncer/inmunología , Antígeno Carcinoembrionario/efectos adversos , Antígeno Carcinoembrionario/genética , Antígeno Carcinoembrionario/inmunología , Protocolos Clínicos , Antígenos de Superficie de la Hepatitis B/efectos adversos , Antígenos de Superficie de la Hepatitis B/genética , Antígenos de Superficie de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/uso terapéutico , Humanos , Plásmidos , VacunaciónRESUMEN
Immunizations with dendritic cells (DC) transfected with RNA encoding tumor antigens induce potent tumor antigen-specific immune responses in vitro and in murine models. We performed a phase I study of patients with advanced carcinoembryonic antigen (CEA)-expressing malignancies followed by a phase II study of patients with resected hepatic metastases of colon cancer to assess safety and feasibility of administering autologous DC loaded with CEA mRNA. The immunizations were well tolerated. Of the 24 evaluable patients in the dose-escalation phase, there was 1 complete response (by tumor marker), 2 minor responses, 3 with stable disease, and 18 with progressive disease. In the phase II study, 9 of 13 patients have relapsed at a median of 122 days. Evidence of an immunologic response was demonstrated in biopsies of DC injection sites and peripheral blood of selected patients. We conclude that it is feasible and safe to administer mRNA-loaded DC to patients with advanced malignancies.