Pre-registration Rigvir® clinical study summary
The Rigvir® clinical studies were started in 1968 in Riga, Latvia. More than 700 patients that had been diagnosed with late stage melanoma, stomach and gastrointestinal tract cancer were involved in the pre-registration safety and efficacy studies [1-5].
Approximately 190 late stage melanoma, stomach and gastrointestinal tract cancer were involved in the Rigvir® safety studies [6-9]. The most commonly observed side effects were sub-febrile temperature, pain in the tumour area, fatigue, sleepiness, and dyspepsia; all were reversible and lasted for a couple of days. There was no intolerance or treatment related discontinuation of treatment.
More than 540 melanoma patients were involved in the Rigvir® efficacy studies. These studies showed that the overall survival was prolonged for patients that had been treated with Rigvir® compared with those, that had been treated with surgery only *. The main Rigvir® clinical studies showed increased 3-year survival in melanoma patients [1, 10-18]. The 3-year survival for patients that had been treated with surgery only was 46-58%, while patients that had also been treated with Rigvir® had a 3-year survival of 57-84% and a 5-year survival of 44-66%. The 3- and 5-year survival for eye melanoma patients were 90% un 70%, respectively.
The safety studies yielded also survival data in the participating approximately 160 stomach and gastrointestinal tract cancer patients. Thus, for stage III stomach cancer patients the 5 year survival post-surgery was 24-33%, compared with 47-60% for those that had also been treated with Rigvir®. Furthermore, for stage II-IV rectum cancer patients the 5 year survival post-surgery was 41-68%, compared with 71-78% for those that had also been treated with Rigvir® [1, 5, 19, 20].
* Now 5-year survival data are required for registration, while for most drugs registered at the turn of the millennium (and are still widely used) such data were not available at the time of approval. Interestingly, the Rigvir® clinical studies conducted during the 1970ies and 1980ies recorded 3- and 5-year survival.
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- Doniņa, S., I. Strēle, G. Proboka, J. Auziņš, P. Alberts, B. Jonsson, D. Venskus, and A. Muceniece, Adapted ECHO-7 virus Rigvir immunotherapy (oncolytic virotherapy) prolongs survival in melanoma patients after surgical excision of the tumour in a retrospective study. Melanoma Research, 2015. 25(5): p. 421-426.
- Alberts, P., E. Olmane, L. Brokāne, Z. Krastiņa, M. Romanovska, K. Kupčs, S. Isajevs, G. Proboka, R. Erdmanis, J. Nazarovs, and D. Venskus, Long-term treatment with the oncolytic ECHO-7 virus Rigvir of a melanoma stage IV M1c patient, a small cell lung cancer stage IIIA patient, and a histiocytic sarcoma stage IV patient-three case reports. APMIS, 2016. 124(10): p. 896-904.
- Alberts, P., L. Brokāne, G. Proboka, D. Venskus, I. Jaunalksne, D. Reihmane, A. Tilgase, V. Telle, L. Patetko, A. Ramata Stunda, and M. Borodušķis, Virotherapy as an independent therapy in oncology: The Latvian model. (In Latvian: Viroterapija kā patstāvīga terapija onkoloğijā: Latvijas modelis.). Latvijas Ārsts, 2016. 5: p. 60-63.
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- Januskevics, V.J., B. Popena, and I. Priedite, Postoperative immunostimulation of patients with colorectal cancer., in Modulation of postoperative anti-tumor immunity (In Russian). 1988, Zinatne: Riga. p. 95-101.
- Kunicina, T.A., J.J. Dmitrievs, and S.L. Tihova, Monitoring of the immunity of skin melanoma patients during the treatment with an enterovirus (In Russian). Symposium “The symptoms and treatment of skin melanomas.” Saratov, 13-14 Sept., 1990.
- Heisele, O., The effect of a viral immunomodulator on the immune reactivity of patients with skin malignant melanoma (In Russian) Thesis. 1987: p. 1-166.
- Rudzītis, M., R. Garklāva, B. Popēna, and I. Desjatnikova, Increased five-year survival of skin melanoma patients undergoing surgical treatment followed by immunomodulator treatment (In Russian). All-Union Symposium “Current issues of immunotherapy of tumours”, Jūrmala, Latvia 19-21 April, 1988. 2:pp. 19-20.
- Grigalinovičs, H., M. Rudzītis, M. Skudra, B. Popēna, I. Desjatnikova, and R. Garklāva, Effect of a viral immunomodulator (Rigvir®) on the morphology and survival of cutaneous melanoma patients (In Russian). Proceedings of the Latvian Academy of Sciences, 1988. 497(12): p. 72-75.
- Muceniece, A., M. Rudzītis, R. Brūvere, I. Desjatnikova, A. Ferdats, R. Garklāva, O. Heisele, B. Popēna, and A. Volrāte, A specially selected and adapted human enterovirus as a biological response modifier with antitumor activity in the treatment of human malignant skin melanoma. Second International Conference on Melanoma, Venice, Poster Sessions, 16-19 October., 1989: p. 316.
- Ferdats, A., Viruses as immunomodulators of antitumour activity (In Russian). Thesis. 1989: p. 1-355.
- Muceniece, A., Rigvir – development of a viral immunomodulator and cancer virotherapy clinical trials (In Latvian). The 4th Latvian Congress of Physicians, Riga, 2001: p. 126-127.
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- Muceniece, A. and D. Venskus, How to assess immunity – the melanoma model. (In Latvian: Kā vērtēt imunitāti – melanomas modelis). 2007.
- Garklāva, R., I. Priedite, and A. Muceniece, Long-term results of surgical treatment of patients with gastric and rectal cancer after immunostimulation with a nonpathogenic enterovirus., in Immunocompetence and immunotherapy of cancer patients (In Russian). 1981: Kemerovo. p. 77-91.
- Muceniece, A., Cancer virotherapy. 1. Retrospection and justification (In Latvian: Ļaundabīgo audzēju viroterapija. 1. daļa – retrospekcija un pamatojums). Doctus, 2005. Nov.: p. 40-44.