Background: Reoviruses are RNA viruses that replicate preferentially in cells with aberrant Ras-pathway signaling. In vitro and in vivo data have shown that the combination of reovirus (REO) and radiation (RT) significantly increases RT-induced cytotoxicity. Material and Methods: Patients (pts) with measurable or evaluable disease amenable to treatment with localised short-course palliative radiotherapy with electrons or orthovoltage X-rays were enrolled in cohorts of 3. Treatment consisted in local tumour irradiation to a dose of 20 Gy in 5 consecutive daily fractions in combination with two intratumoural injections of Reolysin on days 2 and 4 at the following dose-escalation levels: 108, 109 and 1010 tissue culture infectious dose (TCID50). Endpoints were safety, detection of viral replication, evaluation of immune response and antitumoral activity. Results: Six pts have been treated to date (4M/2F) with the following tumor types: metastatic oesophageal cancer to supraclavicular lymph node, metastatic melanoma to skin, abdominal recurrence of pancreatic cancer, recurrent skin squamous carcinoma, metastatic ovarian cancer to skin and locally advanced parotid tumor. One patient at the 1 x 109 dose could not receive the second REO injection due to grade 3 fatigue and grade 2 flu-like symptoms. Other toxicities have been mild (grade 1-2) and have included fever, sweating, skin erythema. There has been no evidence of exacerbation of the acute radiation reaction. Reverse transcription polymerase chain reaction (RT-PCR) studies of blood, urine, stool and sputum on day 8 post-REO administration were negative for viral shedding for all treated pts. Data from neutralising anti-REO antibodies and cellular immune response pre- and post-treatment are being evaluated. Two pts (oesophageal and skin squamous carcinoma) have had significant partial responses (70% and 50%) at 2 and 1 months, respectively, after treatment. In addition, the pt. with metastatic oesophageal cancer had a volume reduction of 15% in the non-irradiated mediastinal disease. Intratumoral viral replication is currently being evaluated by electron microscopy and immunohistochemistry of pre- and post-treatment tumour biopsies.Conclusions: The combination of intratumoral REO and radiation is well tolerated. Local responses and early indicators of systemic effect have been observed. Recruitment is ongoing

[Proc Amer Assoc Cancer Res, Volume 47, 2006]