Safety of glucocorticoids in cancer patients treated with oncolytic adenoviruses.
Oncolytic adenoviruses are an emerging treatment option for advanced and refractory cancer. Such patients are often treated with corticosteroids to ameliorate tumor associated symptoms. Thus, it is important to evaluate whether safety is affected by immunosuppression possibly induced by corticosteroids. Concurrent low-dose cyclophosphamide, appealing for its immunomodulatory effects, could also impact safety. In a retrospective case-control study, we evaluated the effect of systemic corticosteroid use in cancer patients receiving oncolytic virotherapy. Four treatment groups were identified: (1) oncolytic adenovirus with oral glucocorticoids, (2) virus alone, (3) virus with glucocorticoids and cyclophosphamide and (4) virus with cyclophosphamide. Adverse events, neutralizing antibody titers, viral DNA in circulation and tumor responses were evaluated. The most common adverse effects were grade 1-2 fatigue, nausea, fever and abdominal pain. Common asymptomatic findings included self-limiting grade 1-3 hyponatremia and aspartate aminotransferase increase. Safety was good and no significant differences were observed between the groups. All patients had an increase in neutralizing antibody titers post-treatment, and no trends for differences between groups were observed. There were fewer post-treatment virus genomes circulating in patients receiving glucocorticoids when compared to their control groups. Overall, glucocorticoid use in cancer patients receiving oncolytic adenovirus, with or without low-dose cyclophosphamide, seems safe.
Cancer Gene Therapy Group, Transplantation Laboratory and Haartman Institute and Finnish Institute of Molecular Medicine, University of Helsinki, Finland.
Maria
M
Rajecki
Mari
M
Raki
Sophie
S
Escutenaire
Sari
S
Pesonen
Vincenzo
V
Cerullo
Andreas
A
Helminen
Päivi
P
Hannuksela
Kaarina
K
Partanen
Leena
L
Laasonen
Timo
T
Joensuu
Lotta
L
Kangasniemi
Elina
E
Haavisto
Anna
A
Kanerva
Laura
L
Ahtiainen
Akseli
A
Hemminki
D000256:Adenoviridae / Q000235:genetics*; D000328:Adult; D000368:Aged; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000628:therapy*; D050130:Oncolytic Virotherapy / Q000009:adverse effects / Q000379:methods*; D012189:Retrospective Studies; D016896:Treatment Outcome
D005938:Glucocorticoids