The response criteria of evaluation in solid tumors (RECIST) was used to evaluate antitumoral effect. (RECIST) was used to evaluate antitumoral effect. Safety was evaluated by Common Toxicity Criteria of Adverse Event (CTCAE). The vaccine administration was safe and immunogenic in all does levels. Most frequent adverse events related to vaccination were moderate or moderate and were related to injection site reactions and flu-like symptoms. Vaccination induced specific anti-NeuGcGM3 IgM and IgG antibodies responses in all patients. Disease control (objective response or stable disease) was obtained in 72.7% of evaluated patients. Median overall survival was 15.9 months. Two patients of two different dose levels achieved overall survival values of about six years. The dose of 900 g was selected as biological optimal dose in which overall survival was 28.5 months. strong class=”kwd-title” Keywords: metastatic breast cancer, clinical trial, therapeutic vaccine, ganglioside, NGcGM3 Introduction Breast cancer is the most common malignancy and second leading cause of cancer death in females.1 In Cuba, breast malignancy was the leading cause of incidence cancer cases (2981) in 2006. It is the second cause of malignancy mortality in Cuban women (1414 cases in the year 2009) (Data National Malignancy Registry, 2009).2 Most deaths related to breast cancer are the result of complications from metastatic or recurrent disease. In initial presentation, metastatic breast cancer is rare, existing only between 6% to 10% of patients with metastases at diagnosis. Despite advances in cancer treatment, 20% to 85% of patients subsequently develop distant metastases during the first 5 years after initial diagnosis.3 Currently, metastatic breast malignancy is considered incurable and treatment goals are generally palliative. Current treatment options Melanocyte stimulating hormone release inhibiting factor for metastatic breast malignancy consist of schemes based on combined chemotherapy of doxorubicin or taxanes. 4 The response to first-line chemotherapy for metastatic disease may last between 8 and 14 months.5 Once metastasis is detected, the median survival time is within the range of 18 to 24 months.6 The progression of the disease is inevitable and responses in subsequent therapies were progressively lower. The benefit of second-line chemotherapy is usually more controversial, particularly in terms of survival. Chemotherapy beyond the first-line is usually associated with obtaining responses in few patients and there are no consistent or discernible effect on median survival. The effectiveness of second and subsequent lines of chemotherapy is limited to responses in the range of 20% and median survival is usually less than 10 months, Rabbit Polyclonal to GTPBP2 in the range of 6 to 12 months. This is a stimulus for the development of Melanocyte stimulating hormone release inhibiting factor more effective new drugs and new therapeutic strategies.7,8 The gangliosides NGlycosylated gangliosides are very attractive options in immunotherapy as they are over-expressed in tumor cells and minimally or unexpressed in normal human tissue.9C11 Breast malignancy is one tumor that over-expresses NGlycolyl gangliosides, specifically the NGlycolylGM3 gangliosides. Melanocyte stimulating hormone release inhibiting factor 12,13 Others tissues with comparable behavior are melanoma and ovarian cancer. The Center of Molecular Immunology had designed a vaccine based on this ganglioside which has been used in clinical trials in breast cancer patients with a very good toxicity profile and some efficacy evidence. Melanocyte stimulating hormone release inhibiting factor A phase II clinical trial has been conducted in breast cancer patients with NGlycolylGM3/VSSP vaccine administered by intramuscular route using Montanide ISA 51 and an adjuvant.14 This trial showed that this vaccine is safe and immunogenic and some patients achieved values of overall survival superior to reports in literature of those with non-visceral metastases. Two phase III clinical trials were conducted, one in early stage breast cancer patients and the other one in metastatic breast cancer patients.15,16 Despite the vaccine being safe, it was observed that some local reactions may be caused by the adjuvant. For this reason, it was decided to prove the effect of the vaccine by subcutaneous route without adjuvant in comparable patient types. A phase Melanocyte stimulating hormone release inhibiting factor I/II clinical trial was designed to study some dose levels based on dose scaling used by intramuscular route. The main objective of this trial was to determine the biologically optimal dose based on results of safety and efficacy obtained after vaccine administration. Methods Study Participants Thirty-five advanced breast malignancy patients participated in the study recruited at Dr. Celestino Hernandez Robau hospital. Characteristics of patients are given in Table.