A Pilot Feasibility Study of TNFerade™ Biologic with Capecitabine and Radiation Therapy Followed by Surgical Resection for the Treatment of Rectal Cancer

Abstract

<i>Objective:</i> The purpose of this pilot study was to evaluate the feasibility and tolerability of weekly intratumoral TNFerade™ injections combined with concurrent capecitabine and radiotherapy in the treatment of patients with locally advanced rectal cancer. <i>Methods:</i> Patients with T3, T4, or N+ rectal cancer received radiotherapy to a total dose of 50.4–54 Gy in combination with capecitabine 937.5 mg/m<sup>2</sup> p.o. b.i.d. TNFerade™ at a dose of 4 × 10<sup>10</sup> particle units was injected into the rectal tumor on the first day of radiotherapy and weekly for a total of 5 injections. Surgery was performed 5–10 weeks after the completion of chemoradiation. <i>Results:</i> Nine patients were enrolled in this pilot trial. The stage was cT2 in 2 patients, cT3 in 6 patients, cT4 in 1 patient, N– in 7 patients and N+ in 2 patients. Eight patients completed all treatments. Grade 3 hematologic toxicity was observed in 2 patients. There was no toxicity directly attributable to the injection procedure. A complete pathologic response was observed in 2 of 9 patients. <i>Conclusions:</i> This study demonstrates the feasibility of weekly intratumoral TNFerade™ injections during chemoradiotherapy for locally advanced rectal cancer. Pathologic responses with this combination compare favorably to published rates.

In Vivo Screening of S100B Inhibitors for Melanoma Therapy

“…In addition, intratumoral delivery can achieve significantly higher drug concentrations at the site of action than systemic delivery. In the clinical setting, intratumoral administration has been used to deliver gene therapy constructs, complex biologics, and small molecules to a variety of cancers including adenoviral based p53 genes in head and neck cancer (33); TNFalpha genes in rectal cancer (34); interleukin-2 in melanoma (35); immunostimulant CpG in brain cancers (36); single treatment of a meta-static squamous cell carcinoma lesion (37); BCNU in combination with radiotherapy in glioma (38); and para-toluenesulfonamide in non-small cell lung cancer (39). Intratumoral delivery has been used in the preclinical evaluation of siRNAs (40) and immune modulators (41, 42) as well as to reduce the toxicity of approved agents such as melphalan (43); 2-deoxy- D -glucose alone and in combination with carboplatin (44); and paclitaxel/docetaxel in mammary, bladder, prostate, and head and neck cancers (45–48).…”

Immunotherapeutic and Oncolytic Viral Therapeutic Strategies in Pancreatic Cancer

“…Several Phase I investigations have supported these findings in multiple tumor types including head and neck, esophageal, rectal and prostate, among others [160][161][162][163]. A Phase I study using TNFerade in conjunction with radiation therapy in multiple tumors documented partial responses in two of four pancreatic cancer patients.…”

Targeting the death receptor signaling pathway as a potential therapeutic target in the treatment of colorectal cancer

“…A pilot clinical trial of TNFerade was used in nine patients with rectal cancer to evaluate the feasibility and tolerability of intratumoral TNFerade injections. No toxicity was observed related to the injection procedure (Citrin et al, ).…”