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Report of the Southwest Oncology Group

George H. Yoo, MD; James Moon, MS; Michael LeBlanc, PhD; Fulvio Lonardo, MD; Susan Urba, MD; Harold Kim, MD; Ehab Hanna, MD; Terry Tsue, MD; Joseph Valentino, MD; John Ensley, MD; Gregory Wolf, MD

Arch Otolaryngol Head Neck Surg. 2009;135(9):869-874.

Objective  To assess the feasibility of treating patients with high-risk stage III and IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx with perioperative adenovirus-p53 (INGN 201) gene therapy along with surgery and chemoradiotherapy.

Design and Setting  A phase 2 study in a multi-institutional setting within the Southwest Oncology Group.

Patients  Thirteen individuals who met the following entry criteria: newly diagnosed, previously untreated squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx; selected stage III or IV disease without distant metastases; and surgically resectable disease.

Interventions  Surgery, perioperative INGN 201 gene therapy, and postoperative chemoradiotherapy.

Main Outcome Measures  Overall patient status, tumor status, adverse effects, accrual rate, and percentage of patients successfully receiving the required doses of INGN 201.

Results  All 13 patients received surgery and perioperative INGN 201 injections in the primary tumor bed and the ipsilateral neck. In addition, 3 patients received injections in the contralateral neck. Three patients did not receive chemoradiotherapy. One patient had a grade 2 fistula of the oral cavity. Of the 10 patients with evaluable data, 2 experienced grade 4 adverse events, 1 owing to hypokalemia, hyponatremia, vomiting, leukopenia, and neutropenia and 1 owing to increased aspartate aminotransferase and alanine aminotransferase levels. Seven other patients experienced grade 3 adverse events. The estimate of 1-year progression-free survival is 92%.

Conclusions  This trial demonstrated the feasibility of handling and delivering a very complex gene vector safely in multiple cooperative group institutions without significant incident. Intraoperative INGN 201 gene therapy is technically feasible, but it has many logistical problems when performed in a multi-institutional setting. Regulatory requirements might have hindered accrual in this multi-institutional setting. Disease control seems to be promising; however, no definitive conclusion can be made with this small sample size.

Trial Registration  clinicaltrials.gov Identifier: NCT00017173

Author Affiliations: Departments of Otolaryngology (Dr Yoo), Pathology (Dr Lonardo), Radiation Oncology (Dr Kim), and Hematology and Oncology (Dr Ensley), Wayne State University Medical Center, Detroit, Michigan; Southwest Oncology Group Statistical Center, Seattle, Washington (Mr Moon and Dr LeBlanc); Division of Hematology Oncology, Department of Medicine (Dr Urba), and Department of Otolaryngology (Dr Wolf), University of Michigan Medical Center, Ann Arbor; Department of Surgery, M. D. Anderson Cancer Center, Houston, Texas (Dr Hanna); and Departments of Otolaryngology, University of Kansas Medical Center, Kansas City (Dr Tsue), and University of Kentucky Medical Center, Lexington (Dr Valentino).

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