Oncolytic viruses are a fast-developing cancer treatment field. Numerous viruses have been tested in clinical trials and three are approved. The first, Rigvir, is an immunomodulator with anti-tumour effect for treatment of melanoma, local treatment of skin and subcutaneous metastases of melanoma, for prevention of relapse and metastasis after radical surgery registered in Latvia, Georgia, Armenia and Uzbekistan. The aim of the present review is to summarize the development of Rigvir. Approximately 60 viruses were screened preclinically. Clinical safety and efficacy trials were with 5 oncolytic enteroviruses. Safety of the selected and melanoma-adapted ECHO-7 virus Rigvir was tested in over 180 patients with no severe adverse events observed. Pre-registration efficacy studies involved over 700 cancer patients: over 540 melanoma patients, and patients with late stage stomach (ca. 90), colorectal cancer (ca. 60), and other cancers. Patients were treated with Rigvir for 3 years after surgery and compared to immunotherapy: 3- and 5-year overall survival appeared to be increased in Rigvir treated patients. In post-marketing retrospective studies, Rigvir-treated stage II melanoma patients showed a 6.67-fold decreased risk for disease progression in comparison to those that had been observed according to guidelines, and stage IB and stage II melanoma patients that had received Rigvir therapy had 4.39-6.57-fold lower mortality. The results are confirmed and extended by case reports. Several immunological markers have been measured. In conclusion, Rigvir is an oncotropic and oncolytic virus for treatment of melanoma; the results will be confirmed and updated by modern clinical studies.

Patient: Male, 59Final Diagnosis: Chromophobe renal cell carcinoma, stage IVSymptoms: Discomfort in the right hypochondriumMedication: Oncolytic virus RigvirClinical Procedure: Nephro-adrenalectomySpecialty: OncologyObjective:Unusual or unexpected effect of treatmentBackground:Renal cell carcinoma is the most commonly diagnosed primary malignant tumor of the kidney in adults, and includes the variant of chromophobe renal cell carcinoma. Despite new targeted therapies that improve progression-free survival (PFS) and overall survival (OS) for early-stage renal cell carcinoma, the 5-year survival for patients with stage IV renal cell carcinoma remains below 10%, and the 50% OS is less than one year. Metastatic renal cell carcinoma can be resistant to cytotoxic chemotherapy. This report is of a case of stage IV chromophobe renal cell carcinoma that responded well to treatment with the oncolytic ECHO-7 virus, Rigvir®.Case Report:In December 2015, a 59-year-old man presented with a right-sided chromophobe renal cell carcinoma stage IV (pT1N0M1) with adrenal gland metastasis. He underwent right nephro-adrenalectomy followed by treatments with Rigvir® (≥106 TCID50/ml) by intramuscular (i.m.) injection on three consecutive days. Treatment with Rigvir® continued once per week for three months, and from March 2016, once per month, with continued treatment until computed tomography (CT) scans confirmed that the tumor metastases had stabilized.Conclusions:This case report has demonstrated that the oncolytic ECHO-7 virus, Rigvir® should be evaluated further as a potential treatment for advanced renal carcinoma.

There have been a limited number of studies in Latvia that were focused on vancomycin therapeutic drug monitoring (TDM), especially during the initiation phase of the therapy. The aim of this study was to investigate details of vancomycin therapy in its initiation phase and to analyse the results of the first therapeutic drug monitoring within a multidisciplinary hospital in Latvia. A retrospective observational study was performed in a multidisciplinary hospital in Latvia. Adult patients hospitalised in an intensive care unit and undergoing vancomycin therapy with at least one concentration measurement were included in this study. Data about patients included demographic and clinical data, renal function prior to initiation of vancomycin therapy, data about vancomycin therapy, data about the first TDM, and details about the first measurement of vancomycin concentration according to determined reference range — subtherapeutic, therapeutic and supratherapeutic levels. A total of 60 intensive care unit patients who received vancomycin with at least one concentration measurement were included in this study. Fifty-eight patients received vancomycin as intermittent intravenous infusion. The first measurement of concentration was taken before the 3rd–4th vancomycin dose in 38.3% cases, and in 33.3% cases — before the 2nd dose. Sampling to determine the concentration within 30 minutes before vancomycin administration was performed in zero cases. In 35% cases, sampling was done within 2–5 hours before vancomycin administration and in 23.3% — immediately after or within a few hours after vancomycin infusion. Twelve (20%) patients had a concentration in the subtherapeutic level, and 14 (23.3%) patients had concentrations above the therapeutic level. In 42.8% of patients who had concentrations in supratherapeutic level, sampling had been performed immediately after or within several hours after vancomycin administration. The first concentration measurement was performed more than one hour before an infusion in all cases. Data on concentrations and timing were not adequate to perform appropriate therapy modification. Interpretation of dosing regime and concentration results were not adequate, and therefore correct modification of vancomycin therapy was often not possible. Routines of correct dosing regime and the 1st TDM during the initiation phase of vancomycin therapy can be improved.