Abstract C22: A phase II study of intravenous wild-type reovirus (Reolysin®) in combination with paclitaxel plus carboplatin in patients with platinum refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck.
Authors: Karnad Anand B. , Haigentz Missak , Miley Tracy , Coffey Matt , Gill George , Mita Monica 
Published: June 2012

Abstract
Purpose: REOLYSIN® (Reovirus serotype 3) is a Dearing strain, naturally occurring ubiquitous human reovirus. In transformed cells with activated RAS pathway, this reovirus causes preferential lysis due to the inhibition of RNA-activated protein kinase (PKR) in these cells. In a phase-I dose escalation trial three of six patients with squamous cell cancer of the head and neck showed significant responses in combination with chemotherapy leading to the design of this phase-II study.
Methods: A single arm, open-label, phase-II study of REOLYSIN 3 × 1010 TCID50 given intravenously Days 1–5, with paclitaxel (175 mg/m2) and carboplatin (AUC 5) on Day-1 every three weeks was conducted in patients with platinum-refractory recurrent and/or metastatic squamous cell cancers of the oral cavity, larynx, or pharynx. The primary end point was to determine the objective response rate (CR + PR) of the treatment regimen in the study population. Secondary objectives included the determination of disease control rate (CR + PR + SD) and the safety and tolerability of the treatment regimen. Patients were required to have measurable disease and evaluation of tumor status was conducted at baseline and every other cycle.
Results: Since September 2008, 14 patients age 29–61 (median 54) were enrolled and received a total of 57 cycles (range 1–10). Thirteen of 14 patients were ECOG performance status 0 or 1 and 1 was ECOG 2. All patients were platinum-refractory and received other prior chemotherapy, radiotherapy, or combinations for their metastatic or recurrent disease. Ten of 14 patients received prior treatment with taxanes. Sites of disease included larynx (3), oral cavity (6), and pharynx (4), and other site (1). Side effects were mild to moderate (Grade 1–2) including constitutional symptoms, fever, chills, and fatigue. Grade-3 toxicities included hypokalemia (2 patients), fatigue (1), nausea (1), and AST elevation (1). Hematological side effects included Gr-4 neutropenia in 1 patient, Gr-3 neutropenia in 5 patients, and Gr-3 anemia in 3 patients. Thirteen patients were evaluable for response. Four partial responses were seen for an objective response rate of 31%. Two patients had SD for ≥12 weeks for a disease control rate of 46%.Two of the 4 patients with PR and both patients with SD had received prior treatment with taxanes.
Conclusion: REOLYSIN in combination with paclitaxel and carboplatin showed significant activity in patients with platinum-refractory head and neck cancer. An international, randomized, double-blind Phase-III trial of the combination for this target population is under way.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C22.