In the previous clinical studies, a few side effects were reported, for example subfebrile temperature (37.5°C for a couple of days), pain in the tumour area, sleepiness and diarrhoea. In this retrospective study, however, there was no record of any untoward side effect from Rigvir treatment or its discontinuation.
Serum clinical chemistry parameters were recorded and graded according to NCI CTCAE 32 (Table 4). In the observation group, grade 1–3 values were obtained. All grade 3 samples were from two patients obtained within the last few months of life. In one of these patients, progression of the disease was reported simultaneously. In contrast, in the Rigvir-treated patients, values above grade 2 were not observed.
In this study, there was no record of any untoward side effect from Rigvir treatment, which is in agreement with clinical studies using other oncolytic viruses 14,16,33,34,37. Moreover, no value higher than grade 2 was recorded in Rigvir-treated patients. This is in contrast to most other cancer therapies, where grades 3 and 4 are frequently observed (cf. 38).
Administration of virus induces the formation of neutralising antibodies that might potentially influence the efficiency of Rigvir. In previous studies, the titre of neutralising antibodies against ECHO-7 was determined in both healthy individuals and patients before administration of Rigvir. In 94 healthy adult participants tested, the titres were found to be low (1 : 20 to 1 : 62) 39,40. When tested in 155 adult cancer patients who had not been treated with Rigvir, neutralising antibodies against ECHO-7 were detected in ∼50% of the patients 41. In a local study of 472 individuals, the presence of ECHO-7 antibodies was shown to increase with age in children and level off to a plateau of around 75% in adults 42. To our knowledge, the prevalence of neutralising antibodies against the ECHO-7 virus in the general adult population has not been reported.
Also, after intravenous administration, the correlation between antibody titres varies from one virus to another, and neutralising antibodies do not affect efficacy when local or regional administration is used 14,45,46.
An estimated 14.1 million new cancer cases were diagnosed worldwide in 2012, the latest available. The number is expected to increase to 24 million by 2035. About 232 000 patients are estimated to be diagnosed with melanoma in 2014 3. In the 20-year survival data analysis of the American Joint Committee on Cancer (cf. Figure 31.1 of 31), the majority of all melanoma patients belonged to stage I and stage II, 47 and 24%, respectively 31. However, at present, clinical practice guidelines suggest postsurgery therapy only for late-stage melanoma (radiation therapy and interferon α) 6–9.
The authors are indebted to Anna Krilova, Oncology Clinic of Piejūras Hospital, Liepāja, Latvia, for sharing patient information, and Oksana Holodņuka, Riga Eastern Clinical University Hospital, and Linda Brokāne, Latvian Virotherapy Center, for technical assistance, and Vaira Saulīte, Institute of Microbiology and Virology, Riga Stradiņš University, for expert advice.
Aina Muceniece, Dite Venskus, Jurgis Auziņš and Pēteris Alberts are past and present employees of the Latvian Virotherapy Center. For the remaining authors there are no conflicts of interest.
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