Case-control estimation of the impact of oncolytic adenovirus on the survival of patients with refractory solid tumors.
Oncolytic immunotherapy with cytokine armed replication competent viruses is an emerging approach in cancer treatment. In a recent randomized trial, an increase in response rate was seen but the effect on overall survival is not known with any virus. To facilitate randomized trials, we performed a case-control study assessing the survival of 270 patients treated in an Advanced Therapy Access Program (ATAP), in comparison to matched concurrent controls from the same hospital. The overall survival of all virus treated patients was not increased over controls. However, when analysis was restricted to GMCSF-sensitive tumor types treated with GMSCF-coding viruses, a significant improvement in median survival was present (from 170 to 208 days, P = 0.0012, N = 148). An even larger difference was seen when analysis was restricted to good performance score patients (193 versus 292 days, P = 0.034, N = 90). The survival of ovarian cancer patients was especially promising as median survival nearly quadrupled (P = 0.0003, N = 37). These preliminary data lend support to initiation of randomized clinical trials with GMCSF-coding oncolytic adenoviruses.
1] Cancer Gene Therapy Group, Department of Pathology and Transplantation Laboratory, Haartman Institute, Helsinki, Finland [2] Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland.
Anna
A
Kanerva
Cancer Gene Therapy Group, Department of Pathology and Transplantation Laboratory, Haartman Institute, Helsinki, Finland.
Anniina
A
Koski
Cancer Gene Therapy Group, Department of Pathology and Transplantation Laboratory, Haartman Institute, Helsinki, Finland.
Ilkka
I
Liikanen
Cancer Gene Therapy Group, Department of Pathology and Transplantation Laboratory, Haartman Institute, Helsinki, Finland.
Minna
M
Oksanen
Docrates Hospital, Helsinki, Finland.
Timo
T
Joensuu
Cancer Gene Therapy Group, Department of Pathology and Transplantation Laboratory, Haartman Institute, Helsinki, Finland.
Otto
O
Hemminki
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
Juni
J
Palmgren
1] Division of Molecular Genetic Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany [2] Center for Primary Health Care Research, Lund University, Malmö, Sweden.
Kari
K
Hemminki
1] Cancer Gene Therapy Group, Department of Pathology and Transplantation Laboratory, Haartman Institute, Helsinki, Finland [2] Docrates Hospital, Helsinki, Finland [3] TILT Biotherapeutics Ltd, Helsinki, Finland.
Akseli
A
Hemminki
D000256:Adenoviridae / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D055815:Young Adult
D016178:Granulocyte-Macrophage Colony-Stimulating Factor