Clinical Cancer esearch cer Therapy : Clinical-10 : A Phase I Study of Intravenous Reovirus and R etaxel in Patients with Advanced Cancer

wnloade pose: REOLYSIN (Oncolytics Biotech) consists of a wild-type oncolytic reovirus, which has selectotoxicity for tumor cells while sparing normal cells. In a phase I study as a single agent, repeated ons of reovirus were safe with evidence of antitumor activity. Preclinical studies indicate potential nergy between reovirus and chemotherapeutic agents. A multicenter, phase I dose escalation study esigned to assess the safety of combining reovirus with docetaxel chemotherapy in patients with ced cancer. erimental Design: Patients received 75 mg/m docetaxel (day 1) and escalating doses of reovirus 3 × 10 TCID50 (days 1-5) every 3 weeks. ults: Twenty-five patients were enrolled, and 24 patients were exposed to treatment, with 23 comg at least one cycle and 16 suitable for response assessment. Dose-limiting toxicity of grade 4 neuia was seen in one patient, but the maximum tolerated dose was not reached. Antitumor activity en with one complete response and three partial responses. A disease control rate (combined comesponse, partial response, and stable disease) of 88% was observed. Immunohistochemical analysis virus protein expression was observed in posttreatment tumor biopsies from three patients. clusion: The combination of reovirus and docetaxel is safe, with evidence of objective disease ree, and warrants further evaluation in a phase II study at a recommended schedule of docetaxel spons (75 mg/m, three times weekly) and reovirus (3 × 10 TCID50, days 1-5, every 3 weeks). Clin Cancer Res; 16(22); 5564–72. ©2010 AACR.