Specific Immunotherapy in Advanced Cervical-Uterine Cancer Using Humanized Monoclonal Antibody Nimotuzumab and CIMAvax-EGF^®Therapeutic Vaccine

Cervical uterine cancer represents the fourth most common malignant neoplasm worldwide in the female sex in terms of incidence, principally from epithelial origen. The high expression of EGFR in this tumor leads to the search for therapeutic alternatives. An Expanded Access Clinical Program was carried out in parallel groups, randomized, multicenter and prospective study, to evaluate the survival of patients with advanced cervical carcinoma, without therapeutic alternative, who would be treated with the therapeutic vaccine CIMAvax-EGF®, the humanized mAb nimotuzumab or the combination of both products, which targeted EGF and EGFR respectively. The patients were included between 2008 and 2010 with a more than five years follow-up. The results show that the serious adverse events related to the experimental treatments were 0.9%;1.1% and 2.6% and a median ITT survival of 9.1, 23.5, and 16.3 months for CIMAvax-EGF®, nimotuzumab and the combination of both, respectively. Thus fulfilling the hypothesis of safety and efficacy proposed in the investigation was achieved. The three therapeutic regimens achieved overall survival rates greater than 35% at 60 months, encouraging results for advanced uterine cervical cancer. A phase III clinical trial is proposed to consolidate these results in a greater number of patients with nimotuzumab as study drug.

Pharmacokinetics Evaluation of Nimotuzumab in Combination with Doxorubicin and Cyclophosphamide in Patients with Advanced Breast Cancer

EGFr （Epidermal growth factor receptor） overexpression has been detected in many tumors of epithelial origin, specifically in breast cancer and it is often associated with tumor growth advantages and poor prognosis. The nimotuzumab is a genetically engineered humanized MAb （monoclonal antibody） that recognizes an epitope located in the extracellular domain of human EGFr. The aim of this study was to assess the pharmacokinetics of nimotuzumab in patients with locally advanced breast cancer who are receiving neoadyuvant therapy combined with the AC chemotherapy regimen （i.e., 60 mg/m2 of Doxorubicin and 600 mg/m2 of Cyclophosphamide in 4 cycles every 21 days）. A single center, non-controlled, open Phase I clinical trial, with histopathological diagnosis of locally advanced stage III breast cancer, was conducted in 12 female patients. Three patients were enrolled at each of the following fixed dose levels： 50, 100, 200 and 400 mg/week. Multiple intermittent short-term intravenous infusions of nimotuzumab were administered weekly, except on weeks 1 and 10, when blood samples were drawn for pharmacokinetic assessments. Nimotuzumab showed dose-dependent kinetics. No anti-idiotypic response against nimotuzumab was detected in blood samples of participants. There was not interaction between the administration of nimotuzumab and chemotherapy at the dose levels studied. The optimal biological doses ranging were estimated to be 200 mg/weekly to 400 mg/weekly.