2010 ONCY ASCO Abstract Posted - SCCHN
A phase I/II study of oncolytic reovirus plus carboplatin/paclitaxel in patients with advanced solid cancers with emphasis on squamous cell carcinoma of the head and neck (SCCHN).
Sub-category: Other Novel Agents
Category: Developmental Therapeutics - Experimental Therapeutics
Meeting: 2010 ASCO Annual Meeting
Citation: J Clin Oncol 28:7s, 2010 (suppl; abstr 3080)
Abstract No: 3080
Author(s): E. M. Karapanagiotou, J. D. Chester, H. S. Pandha, G. M. Gill, M. C. Coffey, K. Mettinger, K. J. Harrington; The Royal Marsden Hospital, London, United Kingdom; St James's Institute of Oncology, Leeds, United Kingdom; University of Surrey, Guildford, United Kingdom; Clin-Reg Consulting LLP, Alexandria, VA; Oncolytics Biotech, Inc., Calgary, AB, Canada; Oncolytics Biotech, Inc., San Francisco, CA; Royal Marsden Hospital, London, United Kingdom
Abstract:
Background: Reolysin is an isolate of reovirus, a RNA virus which replicates in cells with activated Ras signaling pathway while sparing normal cells. We conducted a phase I/II dose escalation study of intravenous Reolysin in combination with chemotherapy. The study has completed enrollment.
Methods: Reolysin was administered to cohorts of 3 patients in escalating doses (3x109, 1x1010, 3x1010 TCID50) on days 1-5 while carboplatin AUC 5 and paclitaxel 175 mg/m2 were administered on day 1 of a 3-weekly schedule. Eligible patients had good performance status (ECOG PS: 0-2) with advanced cancers which were not amenable to curative treatment or were refractory to standard therapy for which paclitaxel/carboplatin was appropriate palliative chemotherapy.
Results: Thirty-one patients (24 males; median age 59 years) with head and neck cancer (n=24), melanoma (n=4), peritoneal/endometrial cancer (n=2) or sarcoma (n=1) received 147 cycles (median 5, range 1-8) of treatment.
In the dose-escalation phase of the study, there were no dose-limiting toxicities. Grade 3/4 toxicities included anaemia, leucopenia, neutropenia, lymphopenia, thrombocytopenia, infection and hypotension. Neutralising anti-reovirus antibody responses will be presented.
In the phase 1 study, partial responses (PR) were noted in 2 of 5 patients with head and neck cancer.
The Phase 2 study treated head and neck cancer patients at the maximum dose level (3 x 1010 TCID50) in order to further assess tumour response. In total, 19 patients with head and neck cancer received at least 2 cycles and are evaluable for response. Most were SCCHN refractory to previous platinum-based chemotherapy for recurrent/metastatic disease. PR was seen in 8 patients (42%) and SD in 6 (32%). One additional PR and 1 SD were observed among 4 patients with malignant melanoma. Final results for median OS and PFS will be presented.
Conclusions: Intravenous administration of reovirus in combination with carboplatin/paclitaxel is a safe and well-tolerated combination with promising anticancer activity in SCCHN. Further evaluation of this combination in a randomized phase III trial in SCCHN is underway.
