A Phase II Trial of Intratumoral Injection with a Selectively Replicating Adenovirus (ONYX-015) in Patients with Recurrent, Refractory Squamous Cell C

Selectively replicating viruses may offer a new approach to cancer treatment. If successful in clinical trials, these agents will constitute a new category in the antitumoral armamentarium. Many viruses are currently being studied, and an adenovirus (ONYX-015) first entered clinical trials in 1996; herpesvirus agents are scheduled to enter clinical trials in 1998. Critical issues need to be addressed if the utility of these agents is to be optimized. For each virus, the effect of antiviral immunity on antitumoral efficacy must be better understood. For all viruses, physical barriers to spread within tumors (e.g., fibrosis, pressure gradients) must be overcome. Although proof-of-concept experiments with chemotherapy and ONYX-015 have been encouraging, further studies are required to determine optimal treatment-regimen sequencing. Combination studies with radiation therapy are also underway with ONYX-015. Finally, these agents may require modification (e.g., coat modification) in order to maximize effectiveness against systemic metastases following intravenous administration.