Phase I–II trial of ONYX-015 in combination with MAP chemotherapy in patients with advanced sarcomas

Prolonged systemic circulation of chimeric oncolytic adenovirus Ad5/3-Cox2L-D24 in patients with metastatic and refractory solid tumors

“…Rapid clearance of adenovirus from the serum of humans has been shown in several studies, 9,10,24 which led to the proposal that virus detected at 2 days or later may be due to virus replication. [31][32][33] For example, DeWeese et al showed that intraprostatically administered oncolytic adenovirus disappeared from the blood within 12 h. Oncolytic Ad5/3-Cox2L-D24 in cancer patients S Pesonen et al…”

“…This suggests that Ad5/3-Cox2L-D24, at the doses used here, did not induce acute systemic toxicity responses. 23,30 As proposed in previous investigations, [31][32][33] we analyzed Ad5/3-Cox2L-D24 genome copy number in the serum as a surrogate for viral replication. We found virus in the serum of 13 out of 17 patients at least once 2 days or later post treatment, and in 11/14 evaluable cases, the amount increased as compared to day 1.…”

Synergistic anti-tumor effects between oncolytic vaccinia virus and paclitaxel are mediated by the IFN response and HMGB1

“…Indeed, several reports have demonstrated how viral therapies can be effectively combined with chemotherapy, although some viral therapies appear to only be effective in the clinic when used in combination with chemotherapeutic treatments. [10][11][12][13] Although some groups have described mechanisms through which different viral-chemotherapy combinations may result in synergy between the two platforms, these primarily focus on improved killing of already infected cells. For example, paclitaxel treatment has been shown to enhance the ability of an oncolytic adenovirus to replicate, through stabilization of microtubules increasing intracellular movement of the viral particles.…”

Oncolytic viral therapies – the clinical experience

“…Out of 37 patients, 19 exhibited a response to treatment and only 15% of injected tumors had progressed 6 months after treatment initiation. More recently, a phase I/II trial was completed combining ONYX-015 administered intratumorally on days 1-5 every month combined with MAP (mitomycin-C, doxorubicin, cisplatin) chemotherapy in six patients with advanced sarcoma (Galanis et al, 2005). Using a dose escalation from 10 9 PFU/dose up to 10 10 PFU/dose, adenoviral replication was detected in two of six patient biopsies on day 5 of the first cycle and a partial response lasting 11 months was achieved in one patient.…”